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Sun X, Li R, Xiang J. Detection of Klebsiella Pneumoniae and Antibiotic Resistance in Burn Wards in China From 2019 to 2023. Infect Drug Resist 2025; 18:1595-1604. [PMID: 40135047 PMCID: PMC11936408 DOI: 10.2147/idr.s505514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 03/17/2025] [Indexed: 03/27/2025] Open
Abstract
Introduction The rise of antimicrobial resistance in Klebsiella pneumoniae, especially carbapenem-resistant strains (CRKP), presents a major challenge in burn care. This study aimed to examine the detection trends and resistance patterns of K. pneumoniae in burn wards over five years (2019-2023) and analyze the clinical characteristics of patients with CRKP infections during the last three years. Methods A retrospective study was conducted on K. pneumoniae isolates from burn wards, collecting data on bacterial detection and antimicrobial resistance over five years (2019-2023). Clinical records of CRKP-infected patients from the last three years were analyzed, focusing on age, total burn area, third-degree burn area, and prognosis. Statistical analyses assessed resistance trends and correlations between infection outcomes and clinical variables. Results The detection rate of Klebsiella pneumoniae and its resistance to common antibiotics have increased annually, particularly for carbapenem-resistant strains (CRKP). Polymyxin resistance among CRKP isolates has also risen. Wound secretions were the primary infection source, accounting for 75.9% of K. pneumoniae isolates, followed by the respiratory tract at 15.2% and blood/venous catheter samples at 8.9%. There was a significant rise in bloodstream CRKP detection rates during the study period. Clinically, CRKP infections were associated with a larger total burn area (mean: 45.3% vs 28.7% in non-CRKP cases) and more extensive third-degree burns (mean: 22.1% vs 12.4%). Mortality rates were higher in patients with CRKP infections compared to those with carbapenem-susceptible infections (34.6% vs 18.2%). Conclusion The drug-resistant phenomenon of Klebsiella pneumoniae in the burn ward of our hospital was serious, especially the number of carbapenem-resistant antimicrobial drugs of Klebsiella pneumoniae increased significantly, which should be strengthened to monitor and guide the rational use of drugs in the clinic.
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Affiliation(s)
- Xu Sun
- Department of Burn, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Rui Li
- School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China
| | - Jun Xiang
- Department of Burn, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
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Rojek SW, Wojtowicz I, Taccone FS, Duszynska W. Colistin Use for the Treatment of Multi-Drug-Resistant Gram-Negative Severe Infections in ICU Patients: A Single-Center Study. J Clin Med 2025; 14:797. [PMID: 39941468 PMCID: PMC11818872 DOI: 10.3390/jcm14030797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Colistin is increasingly used to treat severe infections caused by multi-drug-resistant (MDR) bacteria, particularly in critically ill patients. Its effectiveness, especially in monotherapy, remains controversial. This study aimed to evaluate the effectiveness and toxicity of colistin therapy in severe MDR infections. Methods: This retrospective study included patients treated with colistin (CMS) at the ICU. Patients' treatments were divided into four subgroups: monotherapy vs. combination therapy, empirical vs. targeted therapy, intravenous vs. intravenous plus inhaled therapy, and standard doses with and without a loading dose. The primary outcome was clinical cure. Secondary outcomes included microbiological eradication, survival rate, and drug-related toxicity, particularly acute kidney injury (AKI). Exclusion criteria included Gram-positive infection, inhaled therapy alone, use of colistin <5 days. Results: A total of 150 patients (mean age 60 ± 18 years, APACHE II score 17 ± 10) were included. The most frequent condition was hospital-acquired pneumonia (n = 140, 93.3%). The most common pathogen was MDR Acinetobacter baumannii (n = 146, 97.3%). In most patients, colistin therapy was targeted (n = 113, 75.3%) and combined with other antibiotics (n = 124, 82.7%). Inhaled CMS was added in 47 (31.3%) patients. Mean duration of therapy was 10 ± 4 days. Clinical cure occurred in 64 (42.7%) patients, microbiological eradication in 20 (13.3%). AKI developed in 65 (53.7%) patients. Inhaled CMS improved the clinical cure rates (57.4% vs. 37.0%, p = 0.003). Conclusions: Intravenous CMS was mainly used for MDR Acinetobacter baumannii-related pneumonia. Clinical cure was observed in 42.7% of patients, but renal toxicity was high. Combining intravenous and inhaled CMS may improve outcomes.
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Affiliation(s)
- Stanislaw Wojciech Rojek
- Department of Anaesthesiology and Intensive Therapy, Saint Bernard’s Hospital, Harbour Views Road, Gibraltar GX11 1AA, Gibraltar;
| | - Iga Wojtowicz
- Department of Anaesthesiology and Intensive Therapy, University Hospital in Wroclaw, Borowska 213 Street, 50-556 Wroclaw, Poland;
| | - Fabio Silvio Taccone
- Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium;
| | - Wieslawa Duszynska
- Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Pasteura Street 1, 50-367 Wroclaw, Poland
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Shettar SR, Sumana MN, Shetty MS, Maheshwarappa YD, Raghukanth RG, Srinivasan A, Vamshi DP, Kalyatanda G, Veerabhadra SGS, Chinchana SE. Case Report: Management of a case of multidrug-resistant Klebsiella pneumoniae infection in a second-kidney transplant patient. FRONTIERS IN TRANSPLANTATION 2025; 3:1494016. [PMID: 39896133 PMCID: PMC11782155 DOI: 10.3389/frtra.2024.1494016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 12/09/2024] [Indexed: 02/04/2025]
Abstract
This case report on recurrent urinary tract infections (UTIs) caused by multidrug-resistant (MDR) Klebsiella pneumoniae in a post-renal transplant patient underscores the significant clinical challenge of managing MDR infections in immunocompromised individuals, particularly in the context of renal transplantation. The patient was treated with an extended infusion of meropenem, which offers prolonged drug exposure and enhances bactericidal activity against MDR pathogens. This approach is critical in overcoming the resistance mechanisms inherent to Klebsiella pneumoniae, thereby improving the likelihood of therapeutic success. The findings presented here highlight the potential efficacy of extended meropenem infusion in treating MDR infections, providing a valuable therapeutic option for clinicians facing similar cases. This report contributes to the growing evidence supporting advanced antibiotic administration techniques in managing complicated urinary tract infections in transplant in resource limited countries.
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Affiliation(s)
- Supreeta R. Shettar
- JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, India
| | | | - Manjunath S. Shetty
- JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, India
| | | | - Reddy G. Raghukanth
- JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, India
| | - Asha Srinivasan
- Department of Nanoscience and Technology, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru, India
| | - Dharan P. Vamshi
- JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, India
| | - Gautam Kalyatanda
- Division of Infectious Disease and Global Medicine, University of Florida, Gainesville, FL, United States
| | - Swamy G. S. Veerabhadra
- JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, India
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Lai C, Ma Z, Zhang J, Wang J, Wang J, Wu Z, Luo Y. Efficiency of combination therapy versus monotherapy for the treatment of infections due to carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis. Syst Rev 2024; 13:309. [PMID: 39702227 DOI: 10.1186/s13643-024-02695-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 10/27/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND For resistant Gram-positive bacteria, evidence suggests that combination therapy is more effective. However, for resistant Gram-negative bacteria, no consensus has been reached. This study aims to comprehensively summarize the evidence and evaluate the impact of combination versus monotherapy on infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB). METHODS A systematic search was conducted in PubMed, Cochrane library, Web of Science, and Embase up to June 15, 2024, to identify relevant studies. This study included comparisons of monotherapy and combination therapy for treating infections caused by CRGNB. Topical antibiotics (i.e., inhalational or intratracheal administration) and monotherapy with sulbactam/relebactam was excluded. The primary outcome was mortality, and the secondary outcomes were clinical success and microbiological eradication. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated in order to systematically assess effect of treatment on mortality, clinical success and microbiological eradication. Subgroup analyses, publication bias tests, and sensitivity analyses were also performed. RESULTS A total of 62 studies, including 8342 participants, were analyzed, comprising 7 randomized controlled trials and 55 non-randomized studies. Monotherapy was associated with higher mortality (OR = 1.29, 95%CI: 1.11-1.51), lower clinical success (OR = 0.74, 95%CI: 0.56-0.98), and lower microbiological eradication (OR = 0.71, 95%CI: 0.55-0.91) compared to combination therapy for CRGNB infections. Specifically, patients with carbapenem-resistant Enterobacteriaceae (CRE) infections receiving monotherapy had higher mortality (OR = 1.50, 95%CI: 1.15-1.95), comparable clinical success (OR = 0.57,95%CI: 0.28-1.16), and lower microbiological eradication (OR = 0.48,95%CI:0.25-0.91) than those receiving combination therapy. For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, no significant differences were observed in mortality (OR = 1.15.95%CI: 0.90-1.47), clinical success (OR = 0.95,95%CI: 0.74-1.24) and microbiological eradication (OR = 0.78,95%CI: 0.54-1.12). CONCLUSIONS Monotherapy or combination therapy is controversial. The systematic review and meta-analysis suggested that monotherapy is associated with higher mortality, lower clinical success, and lower microbiological eradication for treating infection caused by CRGNB. The available evidence suggests that treatment should be selected based on the specific bacteria and antibiotic used. Monotherapy for CRE infections may lead to adverse outcomes. For CRAB infections, no significant differences were found between combination therapy and monotherapy. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42022331861.
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Affiliation(s)
- Chengcheng Lai
- Department of General Practice, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zijun Ma
- Department of General Practice, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jun Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Junjun Wang
- Department of General Practice, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jinghui Wang
- Department of General Practice, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhuanghao Wu
- Department of Neurosurgical Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yonggang Luo
- Department of Neurosurgical Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Huang CF, Yang JL, Chuang YC, Sheng WH. Evaluating Risk Factors for Clinical Failure Among Tigecycline-Treated Patients. Infect Drug Resist 2024; 17:5387-5393. [PMID: 39649431 PMCID: PMC11625427 DOI: 10.2147/idr.s496809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/26/2024] [Indexed: 12/10/2024] Open
Abstract
Purpose Clinical trials have documented that tigecycline has a higher mortality risk than other treatments; it continues to be widely used for various infections in real-world settings, where its associated risk factors for clinical failure are understudied. Patients and Methods This retrospective analysis included a prospective 2019-2021 cohort of tigecycline-treated patients, excluding those with multiple infection sites. We assessed the outcomes on day 28, with clinical failure defined by mortality, persistent initial infection symptoms, or the requirement for continued antimicrobial treatment. Multivariable logistic regression was used for the outcome analysis. Results Of 253 patients included in the study, 94 experienced clinical failure. The infection foci included pneumonia (46.3%), bloodstream infection (BSI) (25.3%), and skin/soft tissue infections (10.3%). There were no significant differences in high-dose tigecycline administration or monotherapy rates between patients with favorable outcomes and those with clinical failure. A higher Charlson comorbidity index (adjusted odds ratio [aOR] = 1.20, P = 0.001), Pitt bacteremia score (aOR = 1.25, P = 0.007), and BSI (aOR = 3.94, P < 0.001) were significant predictors of clinical failure. Concomitant use of Pseudomonas aeruginosa-active fluoroquinolone (aOR = 1.97, P = 0.03) and carbapenem (aOR = 2.20, P = 0.01) was linked to increased clinical failure. Conclusion Multiple comorbidities, BSI, and higher Pitt bacteremia scores are associated with increased risk of clinical failure in tigecycline-treated patients. These results suggest clinicians should consider alternatives to tigecycline for patients with these risk factors. When administering tigecycline, vigilant monitoring is indicated to manage potential clinical failures.
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Affiliation(s)
- Chun-Fu Huang
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan
| | - Jia-Ling Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Chung Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wang-Huei Sheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Wang D, Yang J, Yang L, Du Y, Zhu Q, Ma C, Zhou D. Combination therapy strategies against multidrug resistant bacteria in vitro and in vivo. Lett Appl Microbiol 2024; 77:ovae129. [PMID: 39674809 DOI: 10.1093/lambio/ovae129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 11/30/2024] [Accepted: 12/13/2024] [Indexed: 12/16/2024]
Abstract
Exploring effective combination antibacterial therapies has become a research focus. This study selected seven common antibiotics to perform a series of tests on different Gram-negative bacteria isolated from clinical samples of chronic obstructive pulmonary disease patients. More than 70% of the strains exhibited multidrug resistance but remained sensitive to polymyxin B. The checkerboard assay revealed a significant synergistic effect between polymyxin B and tetracycline against different resistant strains, with fractional inhibitory concentration index values consistently below 0.5. Further time-kill curve analysis demonstrated that the use of minimal inhibit concentration of polymyxin B or tetracycline alone had limited bactericidal effects, while their combination significantly reduced bacterial counts by 2-3 log colony-forming units within 12 h. Additionally, the survival rate of larvae treated with the polymyxin B and tetracycline combination was significantly higher than that of the mono-therapy and untreated groups. In brief, this study demonstrates that the combination of polymyxin B and tetracycline exhibits potent antibacterial activity against multidrug resistant Gram-negative bacteria both in vitro and in vivo.
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Affiliation(s)
- Daliang Wang
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
| | - Jie Yang
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
| | - Lilan Yang
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
| | - Yanglin Du
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
| | - Qunchao Zhu
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
| | - Chendong Ma
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
| | - Dongdong Zhou
- Department of Emergency Medicine, The First People's Hospital Of Jiashan County, Jiaxing 314100 Zhejiang, China
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Yao H, Yang Y, Yao H, Bu S, Li L, Wang F, Zhang J, Chen J. Development of prediction models for carbapenem-resistant Klebsiella pneumoniae acquisition and prognosis in adult patients. Front Pharmacol 2024; 15:1439116. [PMID: 39564105 PMCID: PMC11573532 DOI: 10.3389/fphar.2024.1439116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 10/28/2024] [Indexed: 11/21/2024] Open
Abstract
Objectives To explore the risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection and establish nomograms to predict the probability of CRKP infection and mortality in adult patients. Methods Patients infected with KP from August 2019 to April 2021 in a tertiary hospital in Shanghai were enrolled. Risk factors associated with CRKP and 30-day mortality were identified using multivariate logistic regression analysis and Cox regression analysis. Results Overall, 467 patients with KP infection were enrolled, wherein 210 (45.0%) patients were infected with CRKP and 257 (55.0%) patients with carbapenem-susceptible K. pneumoniae (CSKP). Five factors, namely Charlson's Comorbidity Index (CCI) ≥ 3, the use of central venous catheterization, prior hospitalization during the 3 months before infection, and previous exposure to carbapenems and broad-spectrum β-lactams, were found to be independently associated with CRKP infection. Based on these parameters, the nomogram showed a better performance as indicated by C-index of 0.94 (95% confidence interval [CI]: 0.92-0.96) and well-fitted calibration curves. CRKP was independently associated with 30-day mortality. Multivariate Cox regression analysis revealed that age ≥65 years, higher CCI scores, higher Sequential Organ Failure Assessment scores, the presence of respiratory failure, albumin levels ≤30 g/L, and non-appropriate treatments in 3 days, were associated with 30-day mortality. Conclusion The predictive nomogram established in this study can facilitate the clinicians to make better clinical decisions when treating patients with KP infection.
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Affiliation(s)
- Huijuan Yao
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Yang
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Huimin Yao
- School of Traditional Chinese Medicine, Jilin Agriculture Science and Technology University, Jilin, China
| | - Shuhong Bu
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lixia Li
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fang Wang
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jian Zhang
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jihui Chen
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Semet C, Efe K, Akalın H, İşçimen R, Girgin NK, Özakın C, Cangül N, Kahveci F. Outcome of carbapenem or colistin resistant Klebsiella pneumoniae bacteremia in the intensive care unit. Sci Rep 2024; 14:25805. [PMID: 39468105 PMCID: PMC11519550 DOI: 10.1038/s41598-024-73786-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 09/20/2024] [Indexed: 10/30/2024] Open
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKp) infections continue to be an important cause of mortality. In this retrospective study, the effect of carbapenem or colistin resistance on mortality in Klebsiella pneumoniae bacteremia and combined meropenem + colistin administration in CRKp bacteremia was evaluated. In addition to that, a mathematical model is applied to explore the relationships between the resistance and mortality. A total of 139 adult patients diagnosed with K. pneumoniae bacteremia(73 carbapenem sensitive and 66 carbapenem resistant) between 01/01/2000 and 31/07/2019 were included in the study. The 30-day mortality in entire cohort were 19.4%. 30-day mortality was significantly higher in the carbapenem resistant-colistin sensitive group and in the carbapenem resistant-colistin resistant group compared to the carbapenem susceptible group. Meropenem + colistin combination was administered to 37 (95%) of carbapenem resistant-colistin sensitive (n = 39) and 25 (93%) of carbapenem resistant-colistin resistant patients(n = 27). Notably, mortality was not significantly affected regardless of whether CRKp was colistin sensitive and whether a high dose and prolonged infusion of meropenem was administered. Mortality is higher in carbapenem resistant Klebsiella pneumoniae bacteremia compared to carbapenem susceptible group. In cases of combined meropenem and colistin administration, high dose and prolonged infusion of meropenem is not superior to standard dose and infusion in both carbapenem resistant-colistin sensitive and carbapenem resistant-colistin resistant K. pneumoniae bacteremia.
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Affiliation(s)
- Cihan Semet
- Faculty of Medicine, Dept. of Infectious Diseases and Clinical Microbiology, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
| | - Kadir Efe
- Faculty of Medicine, Dept. of Medical Microbiology, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
| | - Halis Akalın
- Faculty of Medicine, Dept. of Infectious Diseases and Clinical Microbiology, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye.
| | - Remzi İşçimen
- Faculty of Medicine, Dept. of Anesthesiology and Reanimation ICU, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
| | - Nermin Kelebek Girgin
- Faculty of Medicine, Dept. of Anesthesiology and Reanimation ICU, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
| | - Cüneyt Özakın
- Faculty of Medicine, Dept. of Medical Microbiology, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
| | - Naci Cangül
- Faculty of Arts and Science, Department of Mathematics, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
| | - Ferda Kahveci
- Faculty of Medicine, Dept. of Anesthesiology and Reanimation ICU, Bursa Uludağ Univ, Görükle Campus - Nilüfer, 16059, Bursa, Türkiye
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Kaur JN, Klem JF, Liu Y, Boissonneault KR, Holden PN, Kreiswirth B, Chen L, Smith NM, Tsuji BT. Maximally precise combinations to overcome metallo-β-lactamase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2024; 68:e0077024. [PMID: 39287402 PMCID: PMC11459912 DOI: 10.1128/aac.00770-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 08/27/2024] [Indexed: 09/19/2024] Open
Abstract
Gram-negatives harboring metallo-β-lactamases (MBLs) and extended-spectrum β-lactamases (ESBLs) pose a substantial risk to the public health landscape. In ongoing efforts to combat these "superbugs," we explored the clinical combination of aztreonam and ceftazidime/avibactam together with varying dosages of polymyxin B and imipenem against Klebsiella pneumoniae (Kp CDC Nevada) in a 9-day hollow fiber infection model (HFIM). As previously reported by our group, although the base of aztreonam and ceftazidime/avibactam alone leads to 3.34 log10 fold reductions within 72 hours, addition of polymyxin B or imipenem to the base regimen caused maximal killing of 7.55 log10 and 7.4 log10 fold reduction, respectively, by the 72-hour time point. Although low-dose polymyxin B and imipenem enhanced the bactericidal activity as an adjuvant to aztreonam +ceftazidime/avibactam, regrowth to ~9 log10CFU/mL by 216 hours rendered these combinations ineffective. When aztreonam +ceftazidime/avibactam was supplemented with high-dose polymyxin B and or low-dose polymyxin B + imipenem, it resulted in effective long-term clearance of the bacterial population. Time lapse microscopy profiled the emergence of long filamentous cells in response to PBP3 binding due to aztreonam and ceftazidime. The emergence of spheroplasts via imipenem and damage to the outer membrane via polymyxin B was visualized as a mechanism of persister killing. Despite intrinsic mgrB and blaNDM-1 resistance, polymyxin B and β-lactam combinations represent a promising strategy. Future studies using an integrated molecularly precise pharmacodynamic approach are warranted to unravel the mechanistic details to propose optimal antibiotic combinations to combat untreatable, pan-drug-resistant Gram-negatives.
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Affiliation(s)
- Jan Naseer Kaur
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Jack F. Klem
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Yang Liu
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | | | - Patricia N. Holden
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Barry Kreiswirth
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA
| | - Liang Chen
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Nicholas M. Smith
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Brian T. Tsuji
- Center for Infectious Diseases Next Generation Therapeutics, University at Buffalo, Buffalo, New York, USA
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
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Park SY, Baek YJ, Kim JH, Seong H, Kim B, Kim YC, Yoon JG, Heo N, Moon SM, Kim YA, Song JY, Choi JY, Park YS. Guidelines for Antibacterial Treatment of Carbapenem-Resistant Enterobacterales Infections. Infect Chemother 2024; 56:308-328. [PMID: 39231504 PMCID: PMC11458495 DOI: 10.3947/ic.2024.0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/19/2024] [Indexed: 09/06/2024] Open
Abstract
This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.
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Affiliation(s)
- Se Yoon Park
- Division of Infectious Diseases, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
| | - Yae Jee Baek
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jung Ho Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Seong
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Bongyoung Kim
- Division of Infectious Diseases, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Yong Chan Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Infectious Diseases, Yonsei University Yongin Severance Hospital, Yongin, Korea
| | - Jin Gu Yoon
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Namwoo Heo
- Department of Infectious Diseases, Yonsei University Yongin Severance Hospital, Yongin, Korea
| | - Song Mi Moon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young Ah Kim
- Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Joon Young Song
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jun Yong Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Soo Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Infectious Diseases, Yonsei University Yongin Severance Hospital, Yongin, Korea.
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11
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Weston G, Giri A, Komarow L, Ge L, Baum KR, Abbenante E, Gallagher JC, Jacob JT, Kaye KS, Kim AC, Huskins WC, Zervos M, Herc E, Patel R, Van Duin D, Doi Y. Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales. J Antimicrob Chemother 2024; 79:1929-1937. [PMID: 38863337 PMCID: PMC11290877 DOI: 10.1093/jac/dkae186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 05/20/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). OBJECTIVES To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. METHODS Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. RESULTS The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. CONCLUSIONS Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.
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Affiliation(s)
- Gregory Weston
- Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Abhigya Giri
- The Biostatistics Center, George Washington University, Rockville, MD, USA
| | - Lauren Komarow
- The Biostatistics Center, George Washington University, Rockville, MD, USA
| | - Lizhao Ge
- The Biostatistics Center, George Washington University, Rockville, MD, USA
| | - Keri R Baum
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Erin Abbenante
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Jason C Gallagher
- Department of Pharmacy Practice, Temple University School of Pharmacy, Philadelphia, PA, USA
| | - Jesse T Jacob
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Keith S Kaye
- Division of Allergy, Immunology and Infectious Diseases, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Angela C Kim
- Division of Infectious Diseases, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
| | - W Charles Huskins
- Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
| | - Marcus Zervos
- Division of Infectious Diseases, Henry Ford Hospital, Detroit, MI, USA
| | - Erica Herc
- Division of Infectious Diseases, Henry Ford Hospital, Detroit, MI, USA
| | - Robin Patel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - David Van Duin
- Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA
| | - Yohei Doi
- Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Departments of Microbiology and Infectious Diseases, Fujita Health University School of Medicine, Aichi, Japan
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12
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Ngoma N, Perovic O, de Voux A, Musekiwa A, Shuping L. The impact of colistin-based regimens on mortality compared to other antimicrobials in patients with carbapenem-resistant Enterobacterales bacteremia in South African hospitals: a cross-sectional study. BMC Infect Dis 2024; 24:561. [PMID: 38840122 PMCID: PMC11151471 DOI: 10.1186/s12879-024-09459-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 05/31/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Treatment of carbapenem-resistant Enterobacterales (CRE) infections in low-resource settings is challenging particularly due to limited treatment options. Colistin is the mainstay drug for treatment; however, nephrotoxicity and neurotoxicity make this drug less desirable. Thus, mortality may be higher among patients treated with alternative antimicrobials that are potentially less efficacious than colistin. We assessed mortality in patients with CRE bacteremia treated with colistin-based therapy compared to colistin-sparing therapy. METHODS We conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy. RESULTS We included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0-52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873). CONCLUSION In our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed.
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Affiliation(s)
- Nqobile Ngoma
- South African Field Epidemiology Training Programme, National Institute for Communicable Diseases a Division of National Health Laboratory Service, 1 Modderfontein Road, Sandringham, Johannesburg, 2131, South Africa.
- Centre for Healthcare Associated-Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases a Division of National Health Laboratory Service, Johannesburg, South Africa.
- School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
| | - Olga Perovic
- Centre for Healthcare Associated-Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases a Division of National Health Laboratory Service, Johannesburg, South Africa
- Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Alex de Voux
- Division of Epidemiology and Biostatistics, School of Public Health, University of Cape Town, Cape Town, South Africa
| | - Alfred Musekiwa
- School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Liliwe Shuping
- Centre for Healthcare Associated-Infections, Antimicrobial Resistance and Mycoses, National Institute for Communicable Diseases a Division of National Health Laboratory Service, Johannesburg, South Africa
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Ishikawa K, Nakamura T, Kawai F, Ota E, Mori N. Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients. Cancers (Basel) 2024; 16:1934. [PMID: 38792012 PMCID: PMC11487387 DOI: 10.3390/cancers16101934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 05/16/2024] [Accepted: 05/17/2024] [Indexed: 05/26/2024] Open
Abstract
We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. METHOD We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included. RESULT The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, moderate certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01-1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence). CONCLUSION We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.
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Affiliation(s)
- Kazuhiro Ishikawa
- Department of Infectious Diseases, St. Luke’s International Hospital, Tokyo 104-8560, Japan;
| | - Tomoaki Nakamura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke’s International Hospital, Tokyo 104-8560, Japan;
| | - Fujimi Kawai
- Library, Department of Academic Resources, St. Luke’s International University, Tokyo 104-0044, Japan
| | - Erika Ota
- Global Health Nursing, Graduate School of Nursing Sciences, St. Luke’s International University, Tokyo 104-0044, Japan;
- Tokyo Foundation for Policy Research, Tokyo 106-0032, Japan
| | - Nobuyoshi Mori
- Department of Infectious Diseases, St. Luke’s International Hospital, Tokyo 104-8560, Japan;
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Guedes M, Gathara D, López-Hernández I, Pérez-Crespo PMM, Pérez-Rodríguez MT, Sousa A, Plata A, Reguera-Iglesias JM, Boix-Palop L, Dietl B, Blanco JS, Castillo CA, Galán-Sánchez F, Kindelán CN, Jover-Saenz A, Aguirre JG, Alemán AA, Ciordia TM, Del Arco Jiménez A, Fernandez-Suarez J, Lopez-Cortes LE, Rodríguez-Baño J. Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study. Ann Clin Microbiol Antimicrob 2024; 23:42. [PMID: 38711045 PMCID: PMC11071190 DOI: 10.1186/s12941-024-00700-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 04/27/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.
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Affiliation(s)
- Mariana Guedes
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Seville, Spain.
- Infection and Antimicrobial Resistance Control and Prevention Unit, Hospital Epidemiology Centre, Centro Hospitalar Universitário São João, Porto, Portugal.
| | - David Gathara
- London School of Hygiene and Tropical Medicine, MARCH Centre, London, UK
| | - Inmaculada López-Hernández
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Seville, Spain
- CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | | | - María Teresa Pérez-Rodríguez
- Unidad de Enfermedades Infecciosas, Departamento de Medicina Interna, Complexo Hospitalario Universitario de Vigo/Galicia Sur Health Research Institute, Vigo, Spain
| | - Adrian Sousa
- Unidad de Enfermedades Infecciosas, Departamento de Medicina Interna, Complexo Hospitalario Universitario de Vigo/Galicia Sur Health Research Institute, Vigo, Spain
| | - Antonio Plata
- Servicio de Enfermedades Infecciosas, Hospital Regional Universitario de Málaga, IBIMA Málaga, Málaga, Spain
| | - Jose María Reguera-Iglesias
- Servicio de Enfermedades Infecciosas, Hospital Regional Universitario de Málaga, IBIMA Málaga, Málaga, Spain
| | - Lucía Boix-Palop
- Servicio de Enfermedades Infecciosas, Hospital Universitari Mútua de Terrassa, Barcelona, Spain
| | - Beatriz Dietl
- Servicio de Enfermedades Infecciosas, Hospital Universitari Mútua de Terrassa, Barcelona, Spain
| | - Juan Sevilla Blanco
- Unidad de Enfermedades Infecciosas y Microbiologia Clinica, Hospital Universitario Jerez De La Frontera, Jerez De La Frontera, Cádiz, Spain
| | - Carlos Armiñanzas Castillo
- CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - Fátima Galán-Sánchez
- Unidad de Gestión Clínica de Microbiología, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Clara Natera Kindelán
- Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Alfredo Jover-Saenz
- Unidad de Infección Nosocomial, Hospital Universitario Arnau de Vilanova, Lleida, Spain
| | | | - Ana Alemán Alemán
- Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Universitario de Burgos, Burgos, Spain
| | - Teresa Marrodán Ciordia
- Departamento de Microbiología Clínica, Complejo Asistencial Universitario de León (CAULE), León, Spain
| | - Alfonso Del Arco Jiménez
- Grupo Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Costa del Sol, Marbella, Spain
| | - Jonathan Fernandez-Suarez
- Unidad de Microbiología, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Luis Eduardo Lopez-Cortes
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Seville, Spain
- CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | - Jesús Rodríguez-Baño
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Seville, Spain
- CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
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Shao F, Li H, Hsieh K, Zhang P, Li S, Wang TH. Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform. Acta Pharm Sin B 2024; 14:1801-1813. [PMID: 38572105 PMCID: PMC10985126 DOI: 10.1016/j.apsb.2023.11.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 11/22/2023] [Accepted: 11/24/2023] [Indexed: 04/05/2024] Open
Abstract
Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.
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Affiliation(s)
- Fangchi Shao
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Hui Li
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Kuangwen Hsieh
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Pengfei Zhang
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Sixuan Li
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Tza-Huei Wang
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
- Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
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16
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Shaposhnikov LA, Tishkov VI, Pometun AA. Lactobacilli and Klebsiella: Two Opposites in the Fight for Human Health. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:S71-S89. [PMID: 38621745 DOI: 10.1134/s0006297924140050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 04/17/2024]
Abstract
The problem of antibiotic resistance is currently very acute. Numerous research and development of new antibacterial drugs are being carried out that could help cope with various infectious agents. One of the promising directions for the search for new antibacterial drugs is the search among the probiotic strains present in the human gastrointestinal tract. This review is devoted to characteristics of one of these probiotic strains that have been studied to date: Limosilactobacillus reuteri. The review discusses its properties, synthesis of various compounds, as well as role of this strain in modulating various systems of the human body. The review also examines key characteristics of one of the most harmful among the currently known pathogenic organisms, Klebsiella, which is significantly resistant to antibiotics existing in medical practice, and also poses a great threat of nosocomial infections. Discussion of characteristics of the two strains, which have opposite effects on human health, may help in creation of new effective antibacterial drugs without significant side effects.
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Affiliation(s)
- Leonid A Shaposhnikov
- Bach Institute of Biochemistry, Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, 119071, Russia
- Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia
| | - Vladimir I Tishkov
- Bach Institute of Biochemistry, Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, 119071, Russia
- Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia
| | - Anastasia A Pometun
- Bach Institute of Biochemistry, Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, 119071, Russia.
- Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia
- Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), Moscow, 117198, Russia
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Zhang Y, Dong R, Huang Y, Ling X, Ye Z, Jiang S. Acute kidney injury associated with colistin sulfate vs. polymyxin B sulfate therapy: A real-world, retrospective cohort study. Int J Antimicrob Agents 2024; 63:107031. [PMID: 37951480 DOI: 10.1016/j.ijantimicag.2023.107031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 10/25/2023] [Accepted: 11/05/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVE To compare the incidence of acute kidney injury (AKI) in patients treated with colistin sulfate (CS) and polymyxin B sulfate (PMB). METHODS Sociodemographic and laboratory measures of adult patients who received intravenous CS or PMB for at least 72 h for the first time at the study hospital from October 2021 to November 2022 were collected retrospectively. The primary outcome was the incidence of AKI, defined by the Kidney Diseases Improving Global Outcomes criteria. The secondary outcome was 30-day mortality. RESULTS In total, 109 patients were included in the CS cohort and 176 patients were included in the PMB cohort. The incidence of AKI was significantly higher in the PMB cohort compared with the CS cohort (50.6% vs. 18.3%; P<0.001). On multi-variate analysis, CS therapy [hazard ratio (HR) 0.275; P<0.001] was an independent protective factor for AKI, along with higher estimated glomerular filtration rate. Nevertheless, 30-day mortality was similar in the PMB and CS cohorts (21.6% vs. 13.8%; P=0.099). Multi-variate analyses revealed that CS therapy was not associated with 30-day mortality (HR 0.968; P=0.926), while intensive care unit admission, combination with meropenem, Charlson score and stage 3 AKI were independent risk factors for 30-day mortality. After balancing the baseline characteristics of patients using propensity score matching, the main results were unchanged. CONCLUSION The incidence of AKI was significantly lower in the CS cohort compared with the PMB cohort. However, 30-day mortality was similar in the two cohorts.
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Affiliation(s)
- Yanfang Zhang
- Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Rong Dong
- Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yizhen Huang
- Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Xiao Ling
- Department of Pharmacy, The People's Hospital of Yuhuan, Taizhou, Zhejiang, China
| | - Ziqi Ye
- Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Saiping Jiang
- Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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18
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Bayatinejad G, Salehi M, Beigverdi R, Halimi S, Emaneini M, Jabalameli F. In Vitro antibiotic combinations of Colistin, Meropenem, Amikacin, and Amoxicillin/clavulanate against multidrug-resistant Klebsiella pneumonia isolated from patients with ventilator-associated pneumonia. BMC Microbiol 2023; 23:298. [PMID: 37864176 PMCID: PMC10588070 DOI: 10.1186/s12866-023-03039-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 10/03/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP. RESULTS All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60-70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50-70% isolates and the most effective combination was colistin-amikacin with 70% synergy. CONCLUSIONS The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs.
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Affiliation(s)
- Ghazal Bayatinejad
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Salehi
- Department of Infectious Diseases and Tropical Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Beigverdi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahnaz Halimi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Emaneini
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Jabalameli
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Tehran University of Medical Sciences, Tehran, Iran.
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19
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Cui Z, Wang L, Feng M. Clinical and Epidemiological Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Infections in a Tertiary Hospital in China. Microb Drug Resist 2023; 29:401-406. [PMID: 37668594 DOI: 10.1089/mdr.2022.0280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/06/2023] Open
Abstract
Purpose: Infections caused by carbapenem-resistant Klebsiella pneumoniae (CR-KP) are an important public health problem. This study aimed to evaluate the clinical characteristics of patients with CR-KP. Methods: A retrospective cohort study was conducted of all patients with CR-KP infection. A total of 615 patients with CR-KP infection were identified and 135 patients who did not meet the eligibility criteria were excluded. Clinical characteristics, antimicrobial regimens, and patient outcomes were analyzed. Results: The overall mortality rate of CR-KP infections was 37.3% and the mortality rate in patients with bloodstream infections was 66.2%. Survival analysis revealed that there were statistically significant differences between patients with bloodstream infections and those with pulmonary and drainage fluid infections. Logistics regression analysis showed that hemopathy, age >60 years, solid tumors, diabetes, septic shock, acute kidney injury, and stroke were independent predictors of 30-day mortality rate. The chi-square test showed that treatment with a combination of carbapenems, tigecycline, and polymyxin B was superior to treatment with carbapenems with polymyxin B, without tigecycline. Conclusions: CR-KP infections, especially bloodstream infections, have a high mortality rate. The outcome is strongly dependent on patients' clinical conditions. Antimicrobial regimens combining carbapenems, tigecycline, and polymyxin B might be a better choice.
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Affiliation(s)
- Zhiwen Cui
- Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Lirui Wang
- Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Min Feng
- Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Henan, China
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20
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Anton-Vazquez V, Evans TJ, Fernando S, Somasunderam D, David K, Melzer M, Hawkins L, Morris-Jones S, Arias M, Drazho B, Dall’Antonia M, Planche T. Clinical, microbiological characteristics and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study. Infect Prev Pract 2023; 5:100298. [PMID: 37534297 PMCID: PMC10393540 DOI: 10.1016/j.infpip.2023.100298] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/04/2023] [Indexed: 08/04/2023] Open
Abstract
Objectives To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). Methods A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). Results There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. Conclusion Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.
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Affiliation(s)
- Vanesa Anton-Vazquez
- Infection Care Group, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Terry John Evans
- Medical Microbiology, University College London Hospital NHS Foundation Trust, London, UK
| | - Samitha Fernando
- Infectious Diseases and Medical Microbiology, King's College Hospital NHS Foundation Trust, London, UK
| | - Donald Somasunderam
- Department of Infection, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Kate David
- Department of Infection, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Mark Melzer
- Department of Infection, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Lois Hawkins
- Medical Microbiology, Epsom and St. Helier University Hospitals NHS Trust, London, UK
| | - Stephen Morris-Jones
- Medical Microbiology, University College London Hospital NHS Foundation Trust, London, UK
| | - Mauricio Arias
- Infectious Diseases and Medical Microbiology, King's College Hospital NHS Foundation Trust, London, UK
| | - Borana Drazho
- Infectious Diseases and Medical Microbiology, King's College Hospital NHS Foundation Trust, London, UK
| | - Martino Dall’Antonia
- Medical Microbiology, Queen Elizabeth Hospital, Lewisham & Greenwich NHS Trust, London, UK
| | - Timothy Planche
- Infection Care Group, St George's University Hospitals NHS Foundation Trust, London, UK
- Medical Microbiology, Southwest London Pathology, St. George's Hospital, London, UK
- Institute of Infection and Immunity, St. George's University of London, London, UK
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21
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Xiao S, Fu Q, Miao Y, Zhao M, Lu S, Xu J, Zhao W. Clinical efficacy and drug resistance of ceftazidime-avibactam in the treatment of Carbapenem-resistant gram-negative bacilli infection. Front Microbiol 2023; 14:1198926. [PMID: 37664109 PMCID: PMC10469675 DOI: 10.3389/fmicb.2023.1198926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 07/17/2023] [Indexed: 09/05/2023] Open
Abstract
OBJECTIVE To examine the clinical efficacy, safety, and resistance of Ceftazidime-Avibactam (CAZ-AVI) in patients with Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections. METHODS We retrospectively analyzed relevant data of CR-GNB infected patients receiving CAZ-AVI treatment, analyzed relevant factors affecting drug efficacy, and compared the efficacy and safety with patients receiving Polymyxin B treatment. RESULTS A total of 139 patients were included. Agranulocytosis, septic shock, SOFA score, and CAZ-AVI treatment course were independent risk factors affecting the prognosis of patients with CR-GNB infection treated with CAZ-AVI while prolonging the treatment course of CAZ-AVI was the only protective factor for bacterial clearance. The fundamental indicators showed no statistically significant differences between CAZ-AVI and Polymyxin B treatment groups. At the same time, the proportion of patients treated with monotherapy was significantly higher in the CAZ-AVI group than in the Polymyxin B group (37.2% vs. 8.9%, p < 0.05), the 30-day mortality rate of the CAZ-AVI treatment group (27.7% vs. 46.7%, p = 0.027) was lower than that of the Polymyxin B treatment group. The 30-day clinical cure rate (59.6% vs. 40% p = 0.030) and 14-day microbiological clearance rate (42.6% vs. 24.4%, p = 0.038) were significantly higher in the CAZ-AVI than in the Polymyxin B treatment group. Eighty nine patients were monitored for CAZ-AVI resistance, and the total resistance rate was 14.6% (13/89). The resistance rates of Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) to CAZ-AVI were 13.5 and 15.4%, respectively. CONCLUSION CAZ-AVI has shown high clinical efficacy and bacterial clearance in treating CR-GNB infections. Compared with Polymyxin B, CAZ-AVI significantly improved the outcome of mechanical ventilation in patients with septic shock, agranulocytosis, Intensive Care Unit (ICU) patients, bloodstream infection, and patients with SOFA score > 6, and had a lower incidence of adverse events. We monitored the emergence of CAZ-AVI resistance and should strengthen the monitoring of drug susceptibility in clinical practice and the rational selection of antibiotic regimens to delay the onset of resistance.
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Affiliation(s)
- Shuang Xiao
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qianwen Fu
- Department of Critical Care Medicine, The First People’s Hospital of Tonglu, Hangzhou, China
| | - Youhan Miao
- Department of Infectious Diseases, The Third Affiliated Hospital of Nantong University, Nantong, China
| | - Manna Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shengwei Lu
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jie Xu
- Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Weifeng Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China
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22
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Corona A, De Santis V, Agarossi A, Prete A, Cattaneo D, Tomasini G, Bonetti G, Patroni A, Latronico N. Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review. Antibiotics (Basel) 2023; 12:1262. [PMID: 37627683 PMCID: PMC10451333 DOI: 10.3390/antibiotics12081262] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 07/04/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
INTRODUCTION Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. METHODS Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection". RESULTS Current literature data suggest adopting longer (≥10-14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45-50%), MDR (35%), XDR (15-20%), PDR (5.9-6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5-20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5-7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. CONCLUSIONS Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.
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Affiliation(s)
- Alberto Corona
- Accident, Emergency and ICU Department and Surgical Theatre, ASST Valcamonica, University of Brescia, 25043 Breno, Italy
| | | | - Andrea Agarossi
- Accident, Emergency and ICU Department, ASST Santi Paolo Carlo, 20142 Milan, Italy
| | - Anna Prete
- AUSL Romagna, Umberto I Hospital, 48022 Lugo, Italy
| | - Dario Cattaneo
- Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy
| | - Giacomina Tomasini
- Urgency and Emergency Surgery and Medicine Division ASST Valcamonica, 25123 Brescia, Italy
| | - Graziella Bonetti
- Clinical Pathology and Microbiology Laboratory, ASST Valcamonica, 25123 Brescia, Italy
| | - Andrea Patroni
- Medical Directorate, Infection Control Unit, ASST Valcamonica, 25123 Brescia, Italy
| | - Nicola Latronico
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy
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Cai X, Yan H, Zhang W, Zhao W, Zhang L, Wang X, Wu X, Hao Z, Guo J. Intra-abdominal infection after tumor surgery: tigecycline combined with β-lactam antibiotics versus tigecycline alone. BMC Cancer 2023; 23:682. [PMID: 37474892 PMCID: PMC10357740 DOI: 10.1186/s12885-023-11169-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 07/10/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUNDS Tigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus β-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery. METHODS This was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student's t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication. RESULTS In total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time. CONCLUSIONS Tigecycline plus β-lactam wasn't superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.
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Affiliation(s)
- Xinfeng Cai
- Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Zhigongxincun Street 3#, 030012, Taiyuan, Shanxi, P. R. China
| | - Hongxia Yan
- Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Zhigongxincun Street 3#, 030012, Taiyuan, Shanxi, P. R. China
| | - Wenjun Zhang
- Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P. R. China
| | - Wei Zhao
- Department of Pharmacy, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P. R. China
| | - Lei Zhang
- Department of Pharmacy, Shanxi Provincial People's Hospital, Shuangtasi Street 59#, 030001, Taiyuan, Shanxi, P. R. China
| | - Xu Wang
- Department of Literature search, Shanxi Research Center for Information and Strategy of Science and Technology, Taiyuan, Shanxi, P. R. China
| | - Xinjing Wu
- Department of Pharmacy, Yuncheng Central Hospital, Taiyuan, Shanxi, P. R. China
| | - Zhiying Hao
- Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Zhigongxincun Street 3#, 030012, Taiyuan, Shanxi, P. R. China.
| | - Jinlin Guo
- Department of Pharmacy, Shanxi Provincial People's Hospital, Shuangtasi Street 59#, 030001, Taiyuan, Shanxi, P. R. China.
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Stamatiou R, Vasilaki A, Tzini D, Tsolaki V, Zacharouli K, Ioannou M, Fotakopoulos G, Sgantzos M, Makris D. Critical-Illness: Combined Effects of Colistin and Vasoactive Drugs: A Pilot Study. Antibiotics (Basel) 2023; 12:1057. [PMID: 37370376 DOI: 10.3390/antibiotics12061057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/09/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Colistin is often used as a last resort for treating multidrug-resistant infections, particularly in critically ill patients in intensive care units. Nonetheless, its side effects, including myopathy, require careful monitoring. Vasoconstrictive drugs are also used in intensive care to increase blood pressure and improve blood flow to vital organs, which can be compromised in critically ill patients. The exact mechanism of colistin-induced muscle toxicity is of significant interest due to its potential intensive-care clinical implications. Colistin alone or in combination with vasoconstrictive agents was administrated in non-septic and LPS-induced septic animals for 10 days. Histopathological evaluation of the gastrocnemius muscle and dot-blot protein tissue analysis were performed. Increased intramuscular area, de-organization of the muscle fibers and signs of myopathy were observed in colistin-treated animals. This effect was ameliorated in the presence of vasoconstrictive drugs. Administration of colistin to septic animals resulted in a decrease of AMPK and cyclin-D1 levels, while it had no effect on caspase 3 levels. Vasoconstrictive drugs' administration reversed the effects of colistin on AMPK and cyclin D1 levels. Colistin's effects on muscle depend on septic state and vasoconstriction presence, highlighting the need to consider these factors when administering it in critically ill patients.
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Affiliation(s)
- Rodopi Stamatiou
- Physiology Laboratory, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
| | - Anna Vasilaki
- Laboratory of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41221 Larissa, Greece
| | - Dimitra Tzini
- Laboratory of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41221 Larissa, Greece
| | - Vasiliki Tsolaki
- Intensive Care Unit, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
| | - Konstantina Zacharouli
- Pathology Department, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
| | - Maria Ioannou
- Pathology Department, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
| | - George Fotakopoulos
- Department of Neurosurgery, University Hospital of Larissa, 41500 Larisa, Greece
| | - Markos Sgantzos
- Anatomy Department, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
| | - Demosthenes Makris
- Intensive Care Unit, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
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Xu S, Song Z, Han F, Zhang C. Effect of appropriate empirical antimicrobial therapy on mortality of patients with Gram-negative bloodstream infections: a retrospective cohort study. BMC Infect Dis 2023; 23:344. [PMID: 37221465 DOI: 10.1186/s12879-023-08329-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 05/14/2023] [Indexed: 05/25/2023] Open
Abstract
BACKGROUND Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. METHODS This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. RESULTS We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35-0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15-1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86-1.02], p = 0.047). CONCLUSIONS Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.
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Affiliation(s)
- Shanshan Xu
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Zhihui Song
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Furong Han
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Chao Zhang
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
- , No.1 Dongjiaomin Lane, Beijing, Dongcheng District, China.
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Ozyurt OK, Cetinkaya O, Ozhak B, Ongut G, Turhan O, Yazisiz H, Donmez L, Kuskucu MA, Midilli K, Ogunc D. Evaluation of the BD Phoenix CPO Detect Test for the detection of carbapenemase-producing Enterobacterales. Future Microbiol 2023; 18:399-405. [PMID: 37256285 DOI: 10.2217/fmb-2022-0071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 02/24/2023] [Indexed: 06/01/2023] Open
Abstract
Aims: This study aimed to evaluate the performance of the BD Phoenix CPO Detect Test (BD Diagnostic Systems) for the detection and classification of carbapenemase-mediated carbapenem resistance. Methods: A total of 447 Enterobacterales strains were included in the study. All strains were tested with the BD Phoenix CPO Detect Test and the modified carbapenem inactivation method. Results: Carbapenemase production was detected in 157 of 159 carbapenemase producers, including 95.7% of class B and 99.2% of class D isolates using the BD Phoenix CPO Detect Test. BD Phoenix CPO Detect has a sensitivity of 98.7% and a specificity of 95.5% in detecting carbapenemase production. Conclusion: The classification of OXA-48 and class B carbapenemases, the most common carbapenemases circulating in Turkey, was highly accurate.
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Affiliation(s)
- Ozlem K Ozyurt
- Department of Medical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Ozgul Cetinkaya
- Department of Medical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Betil Ozhak
- Department of Medical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Gozde Ongut
- Department of Medical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Ozge Turhan
- Department of Infectious Diseases & Clinical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Hatice Yazisiz
- Department of Medical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Levent Donmez
- Department of Public Health, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Mert A Kuskucu
- Department of Medical Microbiology, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey
| | - Kenan Midilli
- Department of Medical Microbiology, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey
| | - Dilara Ogunc
- Department of Medical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
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Ardebili A, Izanloo A, Rastegar M. Polymyxin combination therapy for multidrug-resistant, extensively-drug resistant, and difficult-to-treat drug-resistant gram-negative infections: is it superior to polymyxin monotherapy? Expert Rev Anti Infect Ther 2023; 21:387-429. [PMID: 36820511 DOI: 10.1080/14787210.2023.2184346] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
INTRODUCTION The increasing prevalence of infections with multidrug-resistant (MDR), extensively-drug resistant (XDR) or difficult-to-treat drug resistant (DTR) Gram-negative bacilli (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter species, and Escherichia coli poses a severe challenge. AREAS COVERED The rapid growing of multi-resistant GNB as well as the considerable deceleration in development of new anti-infective agents have made polymyxins (e.g. polymyxin B and colistin) a mainstay in clinical practices as either monotherapy or combination therapy. However, whether the polymyxin-based combinations lead to better outcomes remains unknown. This review mainly focuses on the effect of polymyxin combination therapy versus monotherapy on treating GNB-related infections. We also provide several factors in designing studies and their impact on optimizing polymyxin combinations. EXPERT OPINION An abundance of recent in vitro and preclinical in vivo data suggest clinical benefit for polymyxin-drug combination therapies, especially colistin plus meropenem and colistin plus rifampicin, with synergistic killing against MDR, XDR, and DTR P. aeruginosa, K. pneumoniae and A. baumannii. The beneficial effects of polymyxin-drug combinations (e.g. colistin or polymyxin B + carbapenem against carbapenem-resistant K. pneumoniae and carbapenem-resistant A. baumannii, polymyxin B + carbapenem + rifampin against carbapenem-resistant K. pneumoniae, and colistin + ceftolozan/tazobactam + rifampin against PDR-P. aeruginosa) have often been shown in clinical setting by retrospective studies. However, high-certainty evidence from large randomized controlled trials is necessary. These clinical trials should incorporate careful attention to patient's sample size, characteristics of patient's groups, PK/PD relationships and dosing, rapid detection of resistance, MIC determinations, and therapeutic drug monitoring.
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Affiliation(s)
- Abdollah Ardebili
- Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ahdieh Izanloo
- Department of Biology, Faculty of Sciences, Golestan University, Gorgan, Iran
| | - Mostafa Rastegar
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
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Havan M, Kendirli T, Parlar ÖT, Özcan S, Yahşi A, Erat T, Öcal D, Guriz H, Özdemir H, Karahan ZC, Çiftci E, İnce E. Clinical Management of a Pandrug-Resistant OXA-48 Klebsiella pneumoniae Infection in the Pediatric Intensive Care Unit. Microb Drug Resist 2023. [PMID: 36912811 DOI: 10.1089/mdr.2022.0247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023] Open
Abstract
Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the serious forms of health care-associated infection. Pan-drug resistant (PDR) CRKP infections can cause severe infections. Mortality and treatment costs in the pediatric intensive care unit (PICU) are high. This study aims to share our experience regarding the treatment of oxacillinase (OXA)-48-positive PDR-CRKP infection in our 20-bed tertiary PICU with isolated rooms and 1 nurse for every 2-3 patients. Methods: Patient demographic characteristics, underlying diseases, previous infections, source of infection PDR-CRKP, treatment modalities, measures used, and outcomes were recorded. Findings: Eleven patients (eight men and three women) were found to have PDR OXA-48-positive CRKP. Because of the simultaneous detection of PDR-CRKP in three patients and the rapid spread of the disease, it was classified as a clinical outbreak, and strict infection control measures were taken. Combination therapy with double carbapenemase (meropenem and imipenem), amikacin, colistin, and tigecycline was used for treatment. The mean duration of treatment and isolation was 15.7 and 65.4 days, respectively. No treatment-related complication was observed, only one patient died, and the mortality rate was 9%. Conclusions: This severe clinical outbreak can be successfully treated with effective treatment with combined antibiotics and strict adherence to infection control measures. ClinicalTrial.gov ID: 28/01/2022 - 1/5.
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Affiliation(s)
- Merve Havan
- Division of Pediatric Critical Care Medicine, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Tanıl Kendirli
- Division of Pediatric Critical Care Medicine, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Özgün Tutku Parlar
- Division of Pediatric Critical Care Medicine, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Serhan Özcan
- Division of Pediatric Critical Care Medicine, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Aysun Yahşi
- Department of Pediatric Infectious Diseases, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Tuğba Erat
- Department of Pediatric Infectious Diseases, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Duygu Öcal
- Department of Microbiology, Ankara University School of Medicine, Ankara, Turkey
| | - Haluk Guriz
- Department of Microbiology, Ankara University School of Medicine, Ankara, Turkey
| | - Halil Özdemir
- Department of Pediatric Infectious Diseases, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Zeynep Ceren Karahan
- Department of Microbiology, Ankara University School of Medicine, Ankara, Turkey
| | - Ergin Çiftci
- Department of Pediatric Infectious Diseases, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Erdal İnce
- Department of Pediatric Infectious Diseases, Ankara University Faculty of Medicine, Ankara, Turkey
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Hanafin PO, Abdul Rahim N, Sharma R, Cess CG, Finley SD, Bergen PJ, Velkov T, Li J, Rao GG. Proof-of-concept for incorporating mechanistic insights from multi-omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae. CPT Pharmacometrics Syst Pharmacol 2023; 12:387-400. [PMID: 36661181 PMCID: PMC10014067 DOI: 10.1002/psp4.12923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 11/21/2022] [Accepted: 12/30/2022] [Indexed: 01/21/2023] Open
Abstract
Carbapenemase-resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time-kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism-based model (MBM) was developed using time-kill data in S-ADAPT describing PMB-CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax : 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one-compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi-omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi-omics responses via a multi-omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2 = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi-omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.
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Affiliation(s)
- Patrick O Hanafin
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | | | - Rajnikant Sharma
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Colin G Cess
- Department of Biomedical Engineering Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA
| | - Stacey D Finley
- Department of Biomedical Engineering Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA
| | - Phillip J Bergen
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Tony Velkov
- Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Victoria, Australia
| | - Jian Li
- Department of Microbiology, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences and Biomedicine Discovery Institute, Monash University, Parkville, Victoria, Australia
| | - Gauri G Rao
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Madney Y, Aboubakr S, Khedr R, Hafez H, Ahmed N, Elsheshtawy K, Elanany M, Salahelden A, Shalaby L, Galal Behairy O. Carbapenem-Resistant Enterobacteriaceae (CRE) among Children with Cancer: Predictors of Mortality and Treatment Outcome. Antibiotics (Basel) 2023; 12:antibiotics12020405. [PMID: 36830314 PMCID: PMC9952844 DOI: 10.3390/antibiotics12020405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/05/2023] [Accepted: 02/10/2023] [Indexed: 02/22/2023] Open
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children's cancer hospital in Egypt (2013-2017). Two hundred and fifty-four pediatric cancer patients with CRE BSI were identified; 74% had hematological malignancies, and 26% had solid tumors. Acute myeloid leukemia was the most common hematological malignancy (50%). The main clinical features for acquiring CRE-BSI were previous antibiotics exposure (90%), profound neutropenia (84%), prolonged steroid use (45%), previous colonization with a resistant pathogen (35%), ICU admission within 90 days (28%), and central venous catheter use (24%). E. coli was the most common isolated pathogen (56%), followed by Klebsiella pneumoniae (37%). All isolates were resistant to carbapenem with an MIC < 4-8 μg/mL in 100 (45%) and >8 μg/mL in 153 (55%). The overall mortality rate was 57%, and 30 day mortality was reported in 30%. Upon multivariate analysis, for the patients with Klebsiella pneumoniae BSI, carbapenem resistance with an MIC > 8 μg/mL and associated typhlitis or pneumonia were predictors of poor outcome. In conclusion, CRE-BSI is a major threat among pediatric cancer patients in limited resource countries with limited options for treatment. Antimicrobial stewardship for early detection through routine screening, adequate empirical treatment, and timely adequate therapy may impact the outcome for such high-risk patient groups.
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Affiliation(s)
- Youssef Madney
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo 12613, Egypt
- Department of Pediatric Oncology, Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Shaimaa Aboubakr
- Department of Paediatrics, Faculty Of Medicine, Benha University, Benha 15881, Egypt
- Correspondence:
| | - Reham Khedr
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo 12613, Egypt
- Department of Pediatric Oncology, Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Hanafy Hafez
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo 12613, Egypt
- Department of Pediatric Oncology, Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Naglaa Ahmed
- Department of Clinical Pharmacy, Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Khaled Elsheshtawy
- Department of Clinical Research, Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Mervat Elanany
- Department of Clinical Microbiology, Faculty Of Medicine, Cairo University and Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Abdelhamid Salahelden
- Department of Paediatrics, Faculty Of Medicine, Benha University, Benha 15881, Egypt
| | - Lobna Shalaby
- Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo 12613, Egypt
- Department of Pediatric Oncology, Children’s Cancer Hospital Egypt, Cairo 57357, Egypt
| | - Ola Galal Behairy
- Department of Paediatrics, Faculty Of Medicine, Benha University, Benha 15881, Egypt
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Soneda K, Uda K, Araki K, Murakoshi T, Yuza Y, Saito O, Kinoshita K, Higuchi H, Horikoshi Y. Clinical characteristics and treatment of IMP-type carbapenemase-producing Enterobacteriaceae bacteremia: Case series and literature review. J Infect Chemother 2023; 29:26-32. [PMID: 36100144 DOI: 10.1016/j.jiac.2022.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 09/02/2022] [Accepted: 09/05/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia. METHODS Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided. RESULTS Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively. CONCLUSIONS We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.
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Affiliation(s)
- Keiko Soneda
- Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
| | - Kazuhiro Uda
- Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan; Department of Pediatrics, Okayama University Hospital, Okayama, Japan
| | - Kotaro Araki
- Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan; Department of Pediatrics, Okinawa Prefectural Yaeyama Hospital, Okinawa, Japan
| | - Takatsugu Murakoshi
- Division of Gastroenterology, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Yuki Yuza
- Division of Hematology and Oncology, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Osamu Saito
- Department of Pediatric Emergency and Critical Care Medicine, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Kazue Kinoshita
- Division of Genetic Laboratory, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Hiroshi Higuchi
- Division of Microbiology, Department of Laboratory, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Yuho Horikoshi
- Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
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Ten Years of KPC-Kp Bloodstream Infections Experience: Impact of Early Appropriate Empirical Therapy on Mortality. Biomedicines 2022; 10:biomedicines10123268. [PMID: 36552024 PMCID: PMC9776375 DOI: 10.3390/biomedicines10123268] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/11/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Background. In K. pneumoniae KPC (KPC-Kp) bloodstream infections (BSI), INCREMENT CPE score >7, Charlson Comorbidity Index (CCI) ≥3 and septic shock are recognized predictors of mortality, with a possible beneficial effect of combination therapy in seriously ill patients. Materials and Methods. We conducted a ten-year retrospective study including all KPC-Kp BSI in patients ≥18 years of age with the aim to evaluate the characteristics and impact of appropriate empirical therapy, either monotherapy or combination therapy, and targeted therapy on mortality. Appropriate therapy was defined as at least one active antimicrobial agent with in vitro activity against KPC-kp demonstrated by susceptibility testing, administered within 48 h from blood culture collection. Results. The median age of the 435 analyzed patients was 66.09 years (IQR 54.87−73.98). The median CCI was 4. KPC-Kp colonization was present in 324 patients (74.48%). The probable origin of the KPC-Kp BSI was not identified in 136 patients (31.26%), whereas in 120 (27.59%) patients, it was CVC-related, and in 118 (27.13%), it was respiratory. Source control was achieved in 87 patients (72.5%) with CVC-related KPC-Kp BSI. The twenty-eight-day survival was 70.45% for empirical monotherapy, 63.88% for empirical combination therapy and 57.05% for targeted therapy (p = 0.0399). A probable source of KPC-Kp BSI other than urinary, CVC or abdominal [aHR 1.64 (IC 1.15−2.34) p = 0.006] and deferred targeted therapy [HR 1.67 (IC 1.12−2.51), p= 0.013] emerged as predictors of mortality, whereas source control [HR 0.62 (IC 0.44−0.86), p = 0.005] and ceftazidime/avibactam administration in empirical therapy [aHR 0.37 (IC 0.20−0.68) p = 0.002] appeared as protective factors. Discussion. These data underline the importance of source control together with timing appropriateness in the early start of empirical therapy over the choice of monotherapy or combination therapy and the use of ceftazidime/avibactam against KPC-Kp BSI.
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Tsai WC, Syue LS, Ko WC, Lo CL, Lee NY. Antimicrobial treatment of monomicrobial phenotypic carbapenem-resistant Klebsiella pneumoniae bacteremia: Two are better than one. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2022; 55:1219-1228. [PMID: 34635426 DOI: 10.1016/j.jmii.2021.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 08/25/2021] [Accepted: 09/04/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUNDS Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are emerging worldwide. The optimal treatment for CRKP infections is challenging for clinicians because therapeutic agents are greatly limited. MATERIAL AND METHODS A retrospective study of CRKP monomicrobial bacteremia was conducted at a medical center between 2010 and 2016. The use of at least one or more drugs with in vitro activity against the blood isolates was defined as appropriate combination therapy. The logistic regression model and propensity score analysis was used to assess clinical effects of therapeutic strategies. The 30-day crude mortality was the primary end point. RESULTS Two hundred and three patients were eligible and the 30-day mortality rate was 37.9% (77 patients). As compared with monotherapy, empirical (11.6 vs. 57.3%, p < .001) or definitive (26.5% vs. 48.6%, p = .001) combination antibiotic therapy showed a lower 30-day mortality rate independently. The propensity score analysis showed that those receiving combination therapy had less clinical (p ≤ .001) or microbiological failure (p = .003) and a lower 30-day mortality rate (p < .001). Among various regimens of definitive therapy, the 30-day mortality rate was the lowest among patients with appropriate combination therapy 23.6%, (p < .001; by log rank test). The primary outcome was similar in those with definitive carbapenem-containing and carbapenem-sparing combination regimens (p = .81). The presence or absence of carbapenemase production did not affect the mortality rate (p = .26). CONCLUSION Combination therapy, regardless of carbapenem-containing or carbapenem-sparing regimens, was associated with a favorable outcome.
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Affiliation(s)
- Wen-Chia Tsai
- Division of Infectious Diseases, Department of Internal Medicine and Tainan, Taiwan
| | - Ling-Shan Syue
- Division of Infectious Diseases, Department of Internal Medicine and Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Wen-Chien Ko
- Division of Infectious Diseases, Department of Internal Medicine and Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ching-Lung Lo
- Division of Infectious Diseases, Department of Internal Medicine and Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, Tainan, Taiwan.
| | - Nan-Yao Lee
- Division of Infectious Diseases, Department of Internal Medicine and Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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An Alliance of Carbapenem-Resistant Klebsiella pneumoniae with Precise Capsular Serotypes and Clinical Determinants: A Disquietude in Hospital Setting. CANADIAN JOURNAL OF INFECTIOUS DISEASES AND MEDICAL MICROBIOLOGY 2022; 2022:6086979. [DOI: 10.1155/2022/6086979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 09/07/2022] [Accepted: 09/27/2022] [Indexed: 11/23/2022]
Abstract
Carbapenemase-resistant Klebsiella pneumoniae (CRKP) is a genuine burden for physicians and researchers. We aimed at carbapenemase resistance and its relation with capsular serotyping in K. pneumoniae and studied some clinical determinants, which may influence the clinical infections. Initially, 61 K. pneumoniae isolates obtained from various clinical specimens were confirmed at the molecular level and then antimicrobial susceptibility test was performed followed by capsular serotyping performed by multiplex PCR. All isolates were subjected to the detection of carbapenemase genes including blaKPC, blaNDM-1, blaOXA-48, blaVIM, and blaIMP. Clinical and demographic data of all patients were reviewed including age, gender, underlying diseases, and the treatment obtained. Multidrug-resistance was a predominant feature in 77% K. pneumoniae strains. Presence of extended-spectrum beta-lactamase was detected phenotypically in 59% K. pneumoniae strains. Carbapenem resistance was noticed phenotypically in 24.6% isolates. blaOXA-48 and blaNDM-1 were the most frequent carbapenemase genes. blaNDM-1 positive isolates correlated with gentamicin, amikacin, imipenem, and meropenem resistance (
). The nosocomial isolates mostly harbored blaOXA-48 gene (
). Amongst all the K. pneumoniae isolates, 59% isolates could be typed and serotype K54 had the highest prevalence followed by K20 and K5. Correlation between the carbapenemase genes, serotype and type of infection showed that blaOXA-48 positive strains had a significant association with K20 serotype and urinary tract infections (
) while, K20 serotype and blaKPC positive strains were significantly associated with wound infections (K20,
and blaKPC, and
). Mucoid phenotype was not found related to presence of specific carbapenemase genes or serotypes except serotype K20 (
). Patients with monotherapy had treatment failure in comparison to the combination therapy for blaKPC-associated infections. In conclusion, the present investigation exhibited the significant association between K20 serotype with blaOXA-48. The predominance of K54 reveals the possibility of endemicity in our hospital setting. K. pneumoniae isolated from wound specimens significantly harbors K20 serotype and blaKPC gene. Comprehensive clinical information and the distribution of antibiotic resistance genes, and serotypes may play important roles in the treatment process.
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Elmanakhly AR, Bendary MM, Safwat NA, Awad EAE, Alhomrani M, Alamri AS, Khafagy ES, Alotaibi HF, Abou-Elazm FI. Carbapenem-Resistant Klebsiella pneumoniae: Diversity, Virulence, and Antimicrobial Resistance. Infect Drug Resist 2022; 15:6177-6187. [PMID: 36312437 PMCID: PMC9597670 DOI: 10.2147/idr.s387742] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 10/13/2022] [Indexed: 11/05/2022] Open
Abstract
Background Klebsiella pneumoniae (K. pneumoniae) is one of the most important pathogens in nosocomial infections. It has resistance to most antibiotics, even carbapenem, resulting in restricted therapeutic options. Purpose We tried to assess the antimicrobial resistance and virulence fitness of carbapenem-resistant K. pneumoniae (CRKP) in addition to their phenotypic and genotypic diversity. Materials and Methods The conventional methods, automated Vitek-32 system, and antimicrobial susceptibility pattern were used to detect CRKP isolates. Virulence and resistance genes profiles were created by using PCR technique. The correlation analysis was done by using R-program. Results The antimicrobial resistance profile for all our K. pneumoniae isolates was shocking as the MDR and CRKP were the most prominent phenotypes. Unfortunately, high degrees of heterogeneity among our CRKP isolates were recorded, as 97.5% of them were differentiated into different clusters. We found a negative correlation between the existence of virulence and antimicrobial resistance genes. In contrast to sputum and urine CRPK isolates, the blood isolates showed high antimicrobial resistance and low virulence fitness. Finally, K. pneumoniae creates several outbreaks and crises in Egypt owing to the highly heterogeneity and the wide spread of multidrug-resistant (MDR) and multi-virulent CRKP phenotypes. Conclusion Our results are significant and alarming to health organizations throughout the world for the severity and heterogeneity of K. pneumoniae infections. Therefore, the traditional method for treatment of CRKP infections must be renewed. Additionally, the treatment protocols must be well correlated with the site of infections, phenotypes, and genotypes of CRKP strains.
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Affiliation(s)
- Arwa R Elmanakhly
- Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, 11559, Egypt
| | - Mahmoud M Bendary
- Microbiology and Immunology Department, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt,Correspondence: Mahmoud M Bendary, Tel +1227550629, Email
| | - Nesreen A Safwat
- Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, 11559, Egypt
| | - Eman Abu-Elnasr Awad
- Department of Internal Medicine, Faculty of Medicine for Girls, Al Azhar University, Cairo, 11559, Egypt
| | - Majid Alhomrani
- Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Science, Taif University, Taif, 26432, Saudi Arabia,Centre of Biomedical Science Research (CBSR), Deanship of Scientific Research, Taif University, Taif, 26432, Saudi Arabia
| | - Abdulhakeem S Alamri
- Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Science, Taif University, Taif, 26432, Saudi Arabia,Centre of Biomedical Science Research (CBSR), Deanship of Scientific Research, Taif University, Taif, 26432, Saudi Arabia
| | - El-Sayed Khafagy
- Department of Pharmaceutics, College of pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj, 11942, Saudi Arabia,Department of Pharmaceutics and Industrial Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Hadil Faris Alotaibi
- Department of Pharmaceutical Science, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, 11671, Saudi Arabia
| | - Fatma I Abou-Elazm
- Department of Microbiology and Immunology, Faculty of Pharmacy, Misr University for Science and Technology, Cairo, 11559, Egypt
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Kardaś-Słoma L, Fournier S, Dupont JC, Rochaix L, Birgand G, Zahar JR, Lescure FX, Kernéis S, Durand-Zaleski I, Lucet JC. Cost-effectiveness of strategies to control the spread of carbapenemase-producing Enterobacterales in hospitals: a modelling study. Antimicrob Resist Infect Control 2022; 11:117. [PMID: 36117231 PMCID: PMC9484055 DOI: 10.1186/s13756-022-01149-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 08/03/2022] [Indexed: 11/24/2022] Open
Abstract
Background Spread of resistant bacteria causes severe morbidity and mortality. Stringent control measures can be expensive and disrupt hospital organization. In the present study, we assessed the effectiveness and cost-effectiveness of control strategies to prevent the spread of Carbapenemase-producing Enterobacterales (CPE) in a general hospital ward (GW). Methods A dynamic, stochastic model simulated the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical 25-bed GW. Input parameters were based on published data; we assumed the prevalence at admission of 0.1%. 12 strategies were compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WSC). Time horizon was one year. Outcomes were the number of CPE acquisitions, costs, and incremental cost-effectiveness ratios (ICER). A hospital perspective was adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or dedicated nursing staff, and lost bed-days due to prolonged hospital stay of identified carriers. The model was calibrated on actual datasets. Sensitivity analyses were performed. Results The baseline scenario resulted in 0.93 CPE acquisitions/1000 admissions and costs 32,050 €/1000 admissions. All control strategies increased costs and improved the outcome. The efficiency frontier was represented by: (1) TS with DNS at a 17,407 €/avoided CPE case, (2) TS + DNS + WSC at a 30,700 €/avoided CPE case and (3) US + DNS + WSC at 181,472 €/avoided CPE case. Other strategies were dominated. Sensitivity analyses showed that TS + CP might be cost-effective if CPE carriers are identified upon admission or if the cases have a short hospital stay. However, CP were effective only when high level of compliance with hand hygiene was obtained. Conclusions Targeted screening at admission combined with DNS for identified CPE carriers with or without weekly screening were the most cost-effective options to limit the spread of CPE. These results support current recommendations from several high-income countries. Supplementary Information The online version contains supplementary material available at 10.1186/s13756-022-01149-0.
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Vidal-Cortés P, Martin-Loeches I, Rodríguez A, Bou G, Cantón R, Diaz E, De la Fuente C, Torre-Cisneros J, Nuvials FX, Salavert M, Aguilar G, Nieto M, Ramírez P, Borges M, Soriano C, Ferrer R, Maseda E, Zaragoza R. Current Positioning against Severe Infections Due to Klebsiella pneumoniae in Hospitalized Adults. Antibiotics (Basel) 2022; 11:antibiotics11091160. [PMID: 36139940 PMCID: PMC9495006 DOI: 10.3390/antibiotics11091160] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/21/2022] [Accepted: 08/25/2022] [Indexed: 11/16/2022] Open
Abstract
Infections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected on the basis of their varied experience in the field of nosocomial infections, who conducted a comprehensive review of the recently published literature on the management of carbapenemase-producing Enterobacterales (CPE) infections in the intensive care setting from 2012 to 2022 to summarize the best available treatment. The group established priorities regarding management, based on both the risk of developing infections caused by K. pneumoniae and the risk of poor outcome. Moreover, we reviewed and updated the most important clinical entities and the new antibiotic treatments recently developed. After analysis of the priorities outlined, this group of experts established a series of recommendations and designed a management algorithm.
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Affiliation(s)
| | - Ignacio Martin-Loeches
- ICU, Trinity Centre for Health Science HRB-Welcome Trust, St. James’s Hospital Dublin, D08 NHY1 Dublin, Ireland
| | - Alejandro Rodríguez
- ICU, Hospital Universitari Joan XXIII, 43005 Tarragona, Spain
- Institut d’Investigació Sanitària Pere Virgil, 43007 Tarragona, Spain
- Departament Medicina I Ciruurgia, Universitat Rovira i Virgili, 43003 Tarragona, Spain
- Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Germán Bou
- Microbiology Department, Complejo Hospitalario Universitario A Coruña, 15006 A Coruña, Spain
- Centro de Investigación en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Rafael Cantón
- Centro de Investigación en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Microbiology Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
| | - Emili Diaz
- Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Critical Care Department, Corporació Sanitària Parc Taulí, 08208 Sabadell, Spain
- Department of Medicine, Universitat Autonoma de Barcelona (UAB), 08193 Barcelona, Spain
| | | | - Julián Torre-Cisneros
- Centro de Investigación en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Infectious Diseases Service, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, 14004 Córdoba, Spain
| | | | - Miguel Salavert
- Infectious Diseases Department, Hospital Universitari I Politecnic La Fe, 46026 Valencia, Spain
| | - Gerardo Aguilar
- SICU, Department of Anesthesiology and Critical Care, Hospital Clínico Universitario Valencia, 46014 Valencia, Spain
- School of Medicine, Universitat de Valencia, 46010 Valencia, Spain
| | - Mercedes Nieto
- ICU, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain
| | - Paula Ramírez
- ICU, Hospital Universitari I Politecnic La Fe, 46026 Valencia, Spain
| | - Marcio Borges
- ICU, Hospital Universitario Son Llázter, 07198 Palma de Mallorca, Spain
- Fundación Micellium, 46183 Valencia, Spain
| | - Cruz Soriano
- ICU, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
| | | | - Emilio Maseda
- Fundación Micellium, 46183 Valencia, Spain
- SICU, Hospital Universitario La Paz, 28046 Madrid, Spain
| | - Rafael Zaragoza
- Fundación Micellium, 46183 Valencia, Spain
- ICU, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
- Correspondence:
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Ruvinsky S, Voto C, Roel M, Deschutter V, Ferraro D, Aquino N, Reijtman V, Galvan ME, Motto E, García M, Sarkis C, Bologna R. Carbapenem-resistant Enterobacteriaceae bloodstream infections: A case-control study from a pediatric referral hospital in Argentina. Front Public Health 2022; 10:983174. [PMID: 36091556 PMCID: PMC9452880 DOI: 10.3389/fpubh.2022.983174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/05/2022] [Indexed: 01/25/2023] Open
Abstract
Background Antibiotic-resistant gram-negative bloodstream infections (BSI) remain a leading cause morbidity and mortality in pediatric patients with a high impact on the public health system. Data in resource-limited countries, including those in Latin America and the Caribbean region, are scarce. The aim of the study was to identify risk factors for acquiring carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in children and to assess the use of resources. Methods A retrospective case-control study was conducted to analyze demographic, epidemiological, clinical, microbiological, and outcome data as well as the use of resources between 2014 and 2019. Univariate and logistic regression analysis was performed in order to identify risk factors associated with CRE-BSI. The R software version 4.1.2 was used. Results A total of 46 cases with CRE-BSI and 92 controls with gram-negative non-CRE-BSI were included. No statistical difference was observed regarding: median age (36 months; IQR, 11.2-117 vs. 48 months, IQR 13-119), male sex (50 vs. 60%), and underlying disease (98 vs. 91%) in cases vs. controls, respectively. The most frequent mechanism of CRE bacteremia were: KPC in 74%, OXA in 15%, and NDM in 6.5%. A total of 54.3% of cases vs. 32.6 % (p = 0.016) of controls were admitted to the pediatric intensive care unit (PICU), and 48 vs. 21% (p = 0.001) required mechanical ventilation. Bacteremia secondary to intra-abdominal infection was observed in 56.5% of cases vs. 35% of controls (p = 0.032). Previous colonization with CRE was detected in 76% of cases vs. 8% of controls. Combination antimicrobial treatment was most frequent in cases vs. control (100 vs. 56.5%). No difference was observed in median length of hospital stay (22 days; IQR, 19-31 in cases vs. 17.5 days; IQR, 10-31 in controls; p = 0.8). Overall case fatality ratio was 13 vs. 5.5%, respectively. The most statistically significant risk factors included previous PICU stay (OR, 4; 95%CI, 2-8), invasive procedures/surgery (OR, 3; 95%CI, 1-7), central venous catheter placement (OR, 6.5; 95%CI, 2-19), urinary catheter placement (OR, 9; 95%CI 4-20), mechanical ventilation (OR, 4; 95%CI, 2-10), liver transplantation (OR, 8; 95%CI, 2-26), meropenem treatment (OR, 8.4; 3.5-22.6) in univariate analysis. The logistic regression model used for multivariate analysis yielded significant differences for previous meropenem treatment (OR, 13; 95%CI, 3-77; p = 0.001), liver transplantation (OR, 13; 95%CI, 2.5-100; p = 0.006), and urinary catheter placement (OR, 9; 95%CI, 1.4-94; p = 0.03). Conclusion CRE-BSI affects hospitalized children with underlying disease, mainly after liver transplantation, with previous urinary catheter use and receiving broad-spectrum antibiotics, leading to high PICU requirement and mortality. These risk factors will have to be taken into account in our region in order to establish adequate health policies and programs to improve antimicrobial stewardship.
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Affiliation(s)
- Silvina Ruvinsky
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina,*Correspondence: Silvina Ruvinsky
| | - Carla Voto
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Macarena Roel
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Verónica Deschutter
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Daiana Ferraro
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Norma Aquino
- Coordinación de Investigación Clínica y Sanitaria, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Vanesa Reijtman
- Servicio de Microbiología, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - María Eugenia Galvan
- Servicio de Terapia Intensiva, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Eduardo Motto
- Servicio de Terapia Intensiva, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Mauro García
- Servicio de Terapia Intensiva, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Claudia Sarkis
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
| | - Rosa Bologna
- Servicio de Infectologia y Epidemiologia, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan, ” Ciudad Autónoma de Buenos Aires, Argentina
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High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy. Sci Rep 2022; 12:12939. [PMID: 35902639 PMCID: PMC9334626 DOI: 10.1038/s41598-022-17083-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 07/20/2022] [Indexed: 12/02/2022] Open
Abstract
The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pandrug-resistant characteristics among CRkp, with a prevalence of 28.5%, which was mediated by chromosomal mgrB, pmrB, or phoQ mutations (91.5%), and plasmid-mediated mcr-1.1, mcr-8.1, mcr-8.2 alone or in conjunction with R256G PmrB (8.5%). Several genetic alterations in mgrB (85.1%) with increased expressions of Ara4N-related phoPQ and pmrK were critical for establishing colistin resistance in our isolates. In this study, we discovered the significant associations between extensively drug-resistant bacteria (XDR) and pandrug-resistant bacteria (PDR) ColRkp in terms of moderate, weak or no biofilm-producing abilities, and altered expressions of virulence factors. These ColRkp would therefore be very challenging to treat, emphasizing for innovative therapy to combat these infections. Regardless of the underlying colistin-resistant mechanisms, colistin-EDTA combination therapy in this study produced potent synergistic effects in both in vitro and in vivo murine bacteremia, with no ColRkp regrowth and improved animal survival, implying the significance of colistin-EDTA combination therapy as systemic therapy for unlocking colistin resistance in ColRkp-associated bacteremia.
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40
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Huang PH, Chen WY, Chou SH, Wang FD, Lin YT. Risk Factors for the Development of Colistin Resistance during Colistin Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections. Microbiol Spectr 2022; 10:e0038122. [PMID: 35652641 PMCID: PMC9241908 DOI: 10.1128/spectrum.00381-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/18/2022] [Indexed: 11/20/2022] Open
Abstract
Colistin is one of the last-resort options for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections if novel antibiotics are unavailable, where the development of colistin resistance during treatment represents a major challenge for clinicians. We aimed to investigate the risk factors associated with the development of colistin resistance in patients with CRKP infections following colistin treatment. We conducted a retrospective case-control study of patients with CRKP strains available before and after colistin treatment at a medical center in Taiwan, between October 2016 and November 2020. Cases (n = 35) included patients with an initial colistin-susceptible CRKP (ColS-CRKP) strain and a subsequent colistin-resistant CRKP (ColR-CRKP) strain. Controls (n = 18) included patients with ColS-CRKP as both the initial and subsequent strains. The 30-day mortality rate after the subsequent CRKP isolation was not different between cases and controls (12/35 [34%] versus 5/18 [28%] [P = 0.631]). blaKPC (n = 38) and blaOXA-48 (n = 11) accounted for the major mechanisms of carbapenem resistance. Alterations in mgrB were found in 18/35 (51%) ColR-CRKP strains, and mcr-1 was not detected in any of the strains. More patients received combination therapy in the control group than in the case group (17/18 versus 21/35 [P = 0.008]). The logistic regression model indicated that combination therapy with tigecycline was protective against the acquisition of colistin resistance (odds ratio, 0.17; 95% confidence interval, 0.05 to 0.62 [P = 0.008]). We observed that the inclusion of tigecycline in colistin treatment mitigated the risk of acquiring colistin resistance. These results offer insight into using the combination of tigecycline and colistin for the treatment of CRKP infections in antimicrobial stewardship. IMPORTANCE Treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is challenging due to the limited options of antibiotics. Colistin is one of the last-resort antibiotics if novel antimicrobial agents are not available. It is crucial to identify modifiable clinical factors associated with the emergence of resistance during colistin treatment. Here, we found that the addition of tigecycline to colistin treatment prevented the acquisition of colistin resistance. Colistin-tigecycline combination therapy is therefore considered a hopeful option in antimicrobial stewardship to treat CRKP infections.
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Affiliation(s)
- Po-Han Huang
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wen-Yin Chen
- Division of Infectious Diseases, Department of Paediatrics, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Sheng-Hua Chou
- Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Fu-Der Wang
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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41
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Yoshida I, Takata I, Fujita K, Takashima H, Sugiyama H. TP0586532, a Novel Non-Hydroxamate LpxC Inhibitor: Potentiating Effect on In Vitro Activity of Meropenem against Carbapenem-Resistant Enterobacteriaceae. Microbiol Spectr 2022; 10:e0082822. [PMID: 35647694 PMCID: PMC9241751 DOI: 10.1128/spectrum.00828-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/10/2022] [Indexed: 12/31/2022] Open
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat to public health requiring the development of novel therapies. TP0586532 is a novel non-hydroxamate LpxC inhibitor that inhibits the synthesis of lipopolysaccharides, which are components of the outer membranes of Gram-negative bacteria. Based on the mechanism of action of TP0586532, we hypothesized that it might enhance the antibacterial activity of other antibiotics by increasing the permeability of the outer bacterial membrane. The combination of TP0586532 with meropenem, amikacin, cefepime, piperacillin, and tigecycline showed synergistic and additive effects against carbapenem-susceptible Klebsiella pneumoniae and Escherichia coli. Checkerboard experiments against 21 carbapenem-resistant K. pneumoniae and E. coli strains (13 blaKPC+, 5 blaNDM-1+, 2 blaVIM+, and 1 blaIMP+) showed that the combination of TP0586532 with meropenem yielded synergistic and additive effects against 9 and 12 strains, respectively. In a time-kill assay examining 12 CRE strains, synergistic effects were observed when TP0586532 was combined with meropenem against many of the strains. A membrane permeability assay using ethidium bromide (EtBr) was performed to investigate the mechanism of the potentiating effect. TP0586532 increased the influx of EtBr into a CRE strain, suggesting that TP0586532 increased membrane permeability and facilitated intracellular access for the antibiotics. Our study demonstrates that TP0586532 potentiates the in vitro antibacterial activity of meropenem against CRE. Combination therapy consisting of TP0586532 and meropenem has potential as a treatment for CRE infections. IMPORTANCE Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health threat, as therapeutic options are limited. TP0586532 is a novel LpxC inhibitor that inhibits the synthesis of lipopolysaccharides in the outer membranes of Gram-negative bacteria. Here, we demonstrated the potentiating effects of TP0586532 on the antibacterial activity of meropenem against CRE harboring various types of carbapenemase genes (blaKPC+, blaNDM-1+ blaVIM+, and blaIMP+). TP0586532 also augmented the bactericidal effects of meropenem against CRE strains, even against those with a high level of resistance to meropenem. The potentiating effects were suggested to be mediated by an increase in bacterial membrane permeability. Our study revealed that a combination therapy consisting of TP0586532 and meropenem has the potential to be a novel therapeutic option for CRE infections.
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Affiliation(s)
- Ippei Yoshida
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan
| | - Iichiro Takata
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan
| | - Kiyoko Fujita
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan
| | - Hajime Takashima
- Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan
| | - Hiroyuki Sugiyama
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan
- Medical Information, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan
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Zhang Y, Zhang R, Sy SKB, Li Z, Zhu S, Zhou M, Song C, Zhang J, Lv Z, Liu J, Qin L, Yu M. Florfenicol/Chlortetracycline Effect on Pharmacodynamic Indices for Mutant Selection of Riemerella anatipestifer in Ducks. Microb Drug Resist 2022; 28:832-840. [PMID: 35723674 DOI: 10.1089/mdr.2022.0008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Riemerella anatipestifer can cause septicemia and death in ducks and geese, leading to significant economic losses to animal farms. The emergence of resistance of R. anatipestifer to commonly used antibiotics increases the difficulty of treating R. anatipestifer infection. The aim of this study was to evaluate the utility of antibiotic combination to restrict mutant selection of multidrug-resistant (MDR) R. anatipestifer isolates. Pharmacokinetics of florfenicol and chlortetracycline in Pekin ducks were evaluated using both noncompartmental analysis and population pharmacokinetic models. The areas under the curve of florfenicol and chlortetracycline after single 20 and 10 mg/kg oral administration were 49.3 and 6.84 mg*h/L, respectively. Chlortetracycline exhibited high apparent clearance and low systemic exposure. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) values of the two antibiotics were determined in 10 and 2 MDR R. anatipestifer isolates, respectively, to derive fTMSW (the fraction of time over 24 hours wherein the free drug concentration was within the mutant selection window [MSW]) and fT>MPC (the fraction of time that the free drug concentration was above the MPC). Both fTMSW and fT>MPC were estimated from simulated concentration-time profiles relative to MIC and MPC. Florfenicol and chlortetracycline combination have additive activities against R. anatipestifer in majority of isolates and could significantly decrease monotherapy MPC of florfenicol and chlortetracycline, as well as optimize both fTMSW and fT>MPC parameters, provided that the bioavailability of chlortetracycline is improved. The application of pharmacokinetic/pharmacodynamic analyses to MPC concepts to restrict selection of mutant bacterial strains can help improve short- and long-term outcomes of antibiotic treatment in animal farms.
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Affiliation(s)
- Yicong Zhang
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China
| | - Ruili Zhang
- Shandong New Hope Liuhe Group Co., Ltd., Qingdao, P.R. China.,Qingdao Jiazhi Biotechnology Co., Ltd., Qingdao, P.R. China
| | - Sherwin K B Sy
- Department of Statistics, State University of Maringá, Maringá, Brazil
| | - Zhizhong Li
- Shandong New Hope Liuhe Group Co., Ltd., Qingdao, P.R. China.,Qingdao Jiazhi Biotechnology Co., Ltd., Qingdao, P.R. China
| | - Shixing Zhu
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China
| | - Meichen Zhou
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China
| | - Chu Song
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China
| | - Jiayuan Zhang
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China
| | - Zhihua Lv
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China.,Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, P.R. China
| | - Jinsong Liu
- Zhejiang Vegamax Biological Technology Co., Ltd., Hangzhou, China
| | - Liting Qin
- Shandong New Hope Liuhe Group Co., Ltd., Qingdao, P.R. China.,Qingdao Jiazhi Biotechnology Co., Ltd., Qingdao, P.R. China
| | - Mingming Yu
- School of Medicine and Pharmacy, Ocean University of China, Qingdao, P.R. China.,Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, P.R. China
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43
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Erdem F, Díez-Aguilar M, Oksuz L, Kayacan C, Abulaila A, Oncul O, Morosini MI, Cantón R, Aktas Z. Time kill-assays of antibiotic combinations for multidrug resistant clinical isolates of OXA-48 carbapenemase producing Klebsiella pneumoniae. Acta Microbiol Immunol Hung 2022; 69:215-219. [PMID: 35895557 DOI: 10.1556/030.2022.01785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 06/02/2022] [Indexed: 11/19/2022]
Abstract
Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study. Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-meropenem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as ≥3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as ≥2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of bla OXA-48, bla NDM, bla VIM, bla IMP, bla KPC and bla CTX-M-1 genes was screened by PCR using specific primers. The bla OXA-48 gene was identified together with bla CTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indifferent effect on the strains. Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism.
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Affiliation(s)
- Fatma Erdem
- 1 Department of Medical Microbiology, Adana City Training and Research Hospital, Department of Medical Microbiology, Adana, Turkey
| | - María Díez-Aguilar
- 2 Servicio de Microbiología, Hospital Universitario La Princesa, Madrid, Spain
| | - Lutfiye Oksuz
- 7 Department of Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Turkey
| | - Cigdem Kayacan
- 3 Department of Medical Microbiology, Faculty of Medicine, Istanbul Aydın University, Turkey
| | - Ayham Abulaila
- 4 Department of Clinical Microbiology, Istinye Faculty of Medicine, Istinye University, Istanbul, Turkey
| | - Oral Oncul
- 5 Department of Infectious Diseases and Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Turkey
| | - María Isabel Morosini
- 6 Servicio de Microbiología. Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Rafael Cantón
- 6 Servicio de Microbiología. Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Zerrin Aktas
- 7 Department of Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Turkey
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Sy CL, Chen PY, Cheng CW, Huang LJ, Wang CH, Chang TH, Chang YC, Chang CJ, Hii IM, Hsu YL, Hu YL, Hung PL, Kuo CY, Lin PC, Liu PY, Lo CL, Lo SH, Ting PJ, Tseng CF, Wang HW, Yang CH, Lee SSJ, Chen YS, Liu YC, Wang FD. Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2022; 55:359-386. [PMID: 35370082 DOI: 10.1016/j.jmii.2022.02.001] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/03/2022] [Accepted: 02/13/2022] [Indexed: 01/12/2023]
Abstract
Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.
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Affiliation(s)
- Cheng Len Sy
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Pao-Yu Chen
- Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Wen Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ling-Ju Huang
- Division of General Medicine, Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taiwan
| | - Ching-Hsun Wang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tu-Hsuan Chang
- Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan
| | - Yi-Chin Chang
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chia-Jung Chang
- Department of Pediatrics, MacKay Children's Hospital and MacKay Memorial Hospital, Taipei, Taiwan
| | - Ing-Moi Hii
- Division of Infectious Diseases, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Lung Hsu
- Division of Pediatric Infectious Diseases, China Medical University Children's Hospital, China Medical University, Taichung, Taiwan
| | - Ya-Li Hu
- Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan
| | - Pi-Lien Hung
- Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chen-Yen Kuo
- Department of Pediatrics, Chang Gung Children's Hospital, College of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Pei-Chin Lin
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Yen Liu
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ching-Lung Lo
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Hao Lo
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Pei-Ju Ting
- Division of Infectious Diseases, Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chien-Fang Tseng
- Department of Pediatrics, MacKay Children's Hospital and MacKay Memorial Hospital, Taipei, Taiwan
| | - Hsiao-Wei Wang
- Division of Infectious Diseases, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Ching-Hsiang Yang
- Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Susan Shin-Jung Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Yao-Shen Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yung-Ching Liu
- Division of Infectious Diseases, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan
| | - Fu-Der Wang
- Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Singh S, Aldawsari HM, Alam A, Alqarni MHS, Ranjan S, Kesharwani P. Synthesis and antimicrobial activity of vancomycin–conjugated zinc coordination polymer nanoparticles against methicillin-resistant staphylococcus aureus. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103255] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Corbella L, Fernández-Ruiz M, Ruiz-Ruigómez M, Rodríguez-Goncer I, Silva JT, Hernández-Jiménez P, López-Medrano F, Lizasoain M, Villa J, Carretero O, Aguado JM, San-Juan R. Prognostic factors of OXA-48 carbapenemase-producing Klebsiella pneumoniae infection in a tertiary-care Spanish hospital: A retrospective single-center cohort study. Int J Infect Dis 2022; 119:59-68. [PMID: 35331934 DOI: 10.1016/j.ijid.2022.03.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 10/18/2022] Open
Abstract
OBJECTIVES To describe the determinants of outcome of infections due to OXA-48 carbapenemase-producing Klebsiella pneumoniae (OXA-48-Kp). METHODS A retrospective cohort study of 117 episodes of OXA-48-Kp infection were conducted. Multivariate Cox models identified factors predicting 14-day clinical response and 30-day all-cause mortality. RESULTS Seventy-seven (65.8%) isolates were susceptible to imipenem/meropenem. 14-day clinical response and 30-day mortality rates were 41.9% and 28.2%. Catheter-related bloodstream infection (adjusted hazard ratio [aHR]: 8.33; 95% confidence interval [95%CI]: 3.19-21.72; P-value <0.001), urinary tract infection (aHR: 3.04; 95%CI: 1.39-6.66; P-value = 0.006) and early appropriate treatment (aHR: 1.77; 95%CI: 0.97-3.22; P-value = 0.064) predicted clinical response, whereas severe sepsis had a deleterious impact (aHR: 0.22; 95%CI: 0.10-0.50; P-value <0.001). Lower respiratory tract infection (aHR: 6.58; 95%CI: 2.83-15.29; P-value <0.001) and bloodstream infection (aHR: 2.33; 95%CI: 1.05-5.15; P-value = 0.037) were associated with 30-day mortality, whereas definitive therapy including ≥1 active agent (aHR: 0.26; 95%CI: 0.11-0.63; P-value = 0.003) and source control (aHR: 0.35; 95%CI: 0.14-0.91; P-value = 0.030) were protective. Combination therapy did not seem to be associated with better outcomes. CONCLUSIONS Appropriate antimicrobial treatment was protective for 30-day mortality in OXA-48-Kp infections. Carbapenems are usually active, whereas combination therapy appeared not to confer additional benefit.
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Affiliation(s)
- Laura Corbella
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain.
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
| | - María Ruiz-Ruigómez
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain.
| | - Isabel Rodríguez-Goncer
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain.
| | - José Tiago Silva
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain.
| | - Pilar Hernández-Jiménez
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain.
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
| | - Manuel Lizasoain
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
| | - Jennifer Villa
- Department of Microbiology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.
| | - Octavio Carretero
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain.
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
| | - Rafael San-Juan
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
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The Role of Colistin in the Era of New β-Lactam/β-Lactamase Inhibitor Combinations. Antibiotics (Basel) 2022; 11:antibiotics11020277. [PMID: 35203879 PMCID: PMC8868358 DOI: 10.3390/antibiotics11020277] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/17/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023] Open
Abstract
With the current crisis related to the emergence of carbapenem-resistant Gram-negative bacteria (CR-GNB), classical treatment approaches with so-called “old-fashion antibiotics” are generally unsatisfactory. Newly approved β-lactam/β-lactamase inhibitors (BLBLIs) should be considered as the first-line treatment options for carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections. However, colistin can be prescribed for uncomplicated lower urinary tract infections caused by CR-GNB by relying on its pharmacokinetic and pharmacodynamic properties. Similarly, colistin can still be regarded as an alternative therapy for infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) until new and effective agents are approved. Using colistin in combination regimens (i.e., including at least two in vitro active agents) can be considered in CRAB infections, and CRE infections with high risk of mortality. In conclusion, new BLBLIs have largely replaced colistin for the treatment of CR-GNB infections. Nevertheless, colistin may be needed for the treatment of CRAB infections and in the setting where the new BLBLIs are currently unavailable. In addition, with the advent of rapid diagnostic methods and novel antimicrobials, the application of personalized medicine has gained significant importance in the treatment of CRE infections.
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Asfour SS, Alaklobi FA, Abdelrahim A, Taha MY, Asfour RS, Khalil TM, Al-Mouqdad MM. Intravenous Ceftazidime-Avibactam in Extremely Premature Neonates With Carbapenem-Resistant Enterobacteriaceae: Two Case Reports. J Pediatr Pharmacol Ther 2022; 27:192-197. [DOI: 10.5863/1551-6776-27.2.192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 06/05/2021] [Indexed: 11/11/2022]
Abstract
The increasing use of carbapenems has contributed to a notable distribution of carbapenem-resistant Enterobacteriaceae (CRE). Recently, the incidence of CRE-associated infections is increasing significantly in NICUs, which pose a grave challenge to clinical treatment. We report 2 cases of IV ceftazidimeavibactam use to treat CRE infections in extremely premature neonates. The first case was diagnosed with bacteraemia and meningitis and the second one was diagnosed with bacteraemia only. Due to the lack of neonatal-specific information for IV ceftazidime-avibactam, the usual pediatric dose (62.5 mg/kg/dose every 8 hours) was used in these patients. Clinical cure occurred in these 2 patients. Although blood cultures became sterile after starting ceftazidime-avibactam in the second case, the patient died, presumably owing to sepsis or various causes, such as prematurity and chronic lung disease. Large and randomized studies are necessary to ensure the safety and efficacy of IV ceftazidime-avibactam for the treatment of neonates with sepsis caused by multidrug resistant organisms.
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Affiliation(s)
- Suzan S. Asfour
- Clinical Pharmacy Department (SSA), King Saud Medical City, Riyadh, Saudi Arabia
| | - Faisal A. Alaklobi
- Pediatric Infectious Disease Department (FAA), King Saud Medical City, Riyadh, Saudi Arabia
| | - Adli Abdelrahim
- Neonatal Intensive Care Unit (AA), King Saud Medical City, Riyadh, Saudi Arabia
| | - Muhammed Y. Taha
- Pediatric Pharmacy Department (MYT), King Saud Medical City, Riyadh, Saudi Arabia
| | - Raneem S. Asfour
- Pharmacy College (RSA), Jordan University of Science and Technology, Irbid, Jordan
| | - Thanaa M. Khalil
- Obstetrics and Gynaecology Department (TMK), King Saud Medical City, Riyadh, Saudi Arabia
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Chen J, Yang Y, Yao H, Bu S, Li L, Wang F, Chen F, Yao H. Prediction of Prognosis in Adult Patients With Carbapenem-Resistant Klebsiella pneumoniae Infection. Front Cell Infect Microbiol 2022; 11:818308. [PMID: 35087768 PMCID: PMC8787092 DOI: 10.3389/fcimb.2021.818308] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 12/20/2021] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with poor patient outcomes. We aimed to analyze the clinical information of adult patients with CRKP infection in order to establish a nomogram for mortality risk as well as to determine the treatment effectiveness of different antimicrobial regimens. METHODS Adult patients diagnosed with CRKP infection in a tertiary hospital in Shanghai between September 2019 and March 2021 were included. The clinical characteristics and clinical outcomes of these patients were analyzed. RESULTS A total of 199 cases of CRKP infection were examined. Five factors, namely age ≥65 years, respiratory failure, Sequential Organ Failure Assessment score, serum procalcitonin ≥5 ng/mL, and appropriate treatments in 3 days, were found to be associated with 30-day mortality. Upon incorporating these factors, the nomogram achieved good concordance indexes of 0.85 (95% confidence interval [CI]: 0.80-0.90) and well-fitted calibration curves. Receiver-operating characteristic curves for 7-, 15-, and 30-day survival had areas under the curve of 0.90, 0.87, and 0.88, respectively. Three-drug combination therapy was observed to be associated with lower mortality in the high-risk group (adjusted hazard ratio = 0.24, 95% CI: 0.06-0.99) but not in the low-risk group. Ceftazidime-avibactam, fosfomycin, and amikacin were effective against infections caused by CRKP. Tigecycline improved the treatment efficiency in 7 days, but a trend toward increased mortality was seen (HR, 1.69; 95% CI: 0.98-2.94; P = 0.061). CONCLUSION The antimicrobial regimen efficacy data and the predictive nomogram established in this study can help clinicians in identifying high-risk adult patients with CRKP infection, improving the therapeutic effect, and reducing mortality.
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Affiliation(s)
- Jihui Chen
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Yang
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Huimin Yao
- School of Pharmacy and Medicine, Tonghua Normal University, Jilin, China
| | - Shuhong Bu
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lixia Li
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fang Wang
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Feng Chen
- Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Huijuan Yao
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Nguyen HT, Venter H, Woolford L, Young K, McCluskey A, Garg S, Page SW, Trott DJ, Ogunniyi AD. Impact of a Novel Anticoccidial Analogue on Systemic Staphylococcus aureus Infection in a Bioluminescent Mouse Model. Antibiotics (Basel) 2022; 11:antibiotics11010065. [PMID: 35052942 PMCID: PMC8773087 DOI: 10.3390/antibiotics11010065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/27/2021] [Accepted: 01/01/2022] [Indexed: 02/05/2023] Open
Abstract
In this study, we investigated the potential of an analogue of robenidine (NCL179) to expand its chemical diversity for the treatment of multidrug-resistant (MDR) bacterial infections. We show that NCL179 exhibits potent bactericidal activity, returning minimum inhibitory concentration/minimum bactericidal concentrations (MICs/MBCs) of 1–2 µg/mL against methicillin-resistant Staphylococcus aureus, MICs/MBCs of 1–2 µg/mL against methicillin-resistant S. pseudintermedius and MICs/MBCs of 2–4 µg/mL against vancomycin-resistant enterococci. NCL179 showed synergistic activity against clinical isolates and reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in the presence of sub-inhibitory concentrations of colistin, whereas NCL179 alone had no activity. Mice given oral NCL179 at 10 mg/kg and 50 mg/kg (4 × doses, 4 h apart) showed no adverse clinical effects and no observable histological effects in any of the organs examined. In a bioluminescent S. aureus sepsis challenge model, mice that received four oral doses of NCL179 at 50 mg/kg at 4 h intervals exhibited significantly reduced bacterial loads, longer survival times and higher overall survival rates than the vehicle-only treated mice. These results support NCL179 as a valid candidate for further development to treat MDR bacterial infections as a stand-alone antibiotic or in combination with existing antibiotic classes.
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Affiliation(s)
- Hang Thi Nguyen
- Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia;
- Department of Pharmacology, Toxicology, Internal Medicine and Diagnostics, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi 100000, Vietnam
| | - Henrietta Venter
- Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia;
| | - Lucy Woolford
- School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, Roseworthy, SA 5371, Australia;
| | - Kelly Young
- Chemistry, School of Environmental & Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia; (K.Y.); (A.M.)
| | - Adam McCluskey
- Chemistry, School of Environmental & Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia; (K.Y.); (A.M.)
| | - Sanjay Garg
- Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia;
| | | | - Darren J. Trott
- Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia;
- Correspondence: (D.J.T.); (A.D.O.); Tel.: +61-8-8313-7989 (D.J.T.); +61-432331914 (A.D.O.); Fax: +61-8-8313-7956 (D.J.T.)
| | - Abiodun David Ogunniyi
- Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia;
- Correspondence: (D.J.T.); (A.D.O.); Tel.: +61-8-8313-7989 (D.J.T.); +61-432331914 (A.D.O.); Fax: +61-8-8313-7956 (D.J.T.)
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