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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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Sakulkonkij P, Bruminhent J. Epidemiology, Clinical Characteristics and Treatment Outcomes of Acinetobacter baumannii Infection at a Regional Hospital in Thailand. Infect Drug Resist 2025; 18:473-482. [PMID: 39882251 PMCID: PMC11776409 DOI: 10.2147/idr.s494712] [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: 09/10/2024] [Accepted: 01/15/2025] [Indexed: 01/31/2025] Open
Abstract
Objective This retrospective cohort study evaluated the treatment outcome of Acinetobacter baumannii infection. Methods In this retrospective cohort study, 476 patients with Acinetobacter baumannii (A. baumannii) infection who were admitted to the internal medicine ward at Lampang Hospital, Lampang, Thailand, from 1 January 2020 to 31 December 2020 were enrolled. Medical records were reviewed. Results A total of 476 patients with A. baumannii infection were enrolled. Of these, 204 (43%) survived, while 272 (57%) died. Extensively drug-resistant (XDR) A. baumannii with hospital-acquired pneumonia was the most common presentation. Risk factors for acquiring multidrug-resistant (MDR) pathogens included previous hospitalization or antibiotic use and the presence of an indwelling urinary catheter, which was common in both survived and deceased groups. The survival group was significantly more likely to have received appropriate antibiotic therapy compared to the deceased group (71% vs 51%; p<0.001), particularly with colistin monotherapy (34% vs 18%; p<0.001). Additionally, multivariate analysis showed that predictors of unfavorable outcomes, such as multiorgan failure, hypoalbuminemia, hematologic malignancy, and healthcare-associated pneumonia. The survival group had a significantly longer hospital stay compared to the deceased group (15 days vs 7 days; p<0.001) and also showed an increased microbiological cure rate (49% vs 26%; p<0.001). Conclusion XDR A. baumannii leads to serious nosocomial infections. Understanding the risk factors for XDR A. baumannii infections could enhance colistin prescription prior to the antimicrobial susceptibility testing results.
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Affiliation(s)
- Parichart Sakulkonkij
- Division of Infectious Diseases, Internal Medicine Department, Lampang Hospital, Lampang, Thailand
| | - Jackrapong Bruminhent
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Choi H, Min KH, Lee YS, Chang Y, Lee BY, Oh JY, Baek AR, Lee J, Jeon K. Korean Guidelines for the Management and Antibiotic Therapy in Adult Patients with Hospital-Acquired Pneumonia. Tuberc Respir Dis (Seoul) 2025; 88:69-89. [PMID: 39391954 PMCID: PMC11704733 DOI: 10.4046/trd.2024.0135] [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: 09/16/2024] [Accepted: 10/08/2024] [Indexed: 10/12/2024] Open
Abstract
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.
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Affiliation(s)
- Hayoung Choi
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea
| | - Kyung Hoon Min
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Young Seok Lee
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Youjin Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, Republic of Korea
| | - Bo Young Lee
- Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Jee Youn Oh
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Ae-Rin Baek
- Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Jongmin Lee
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyeongman Jeon
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Heng H, Yang L, Zheng Z, Yang C, Yang X, Zhao W, Sun R, Chen K, Ye L, Li J, Chan EWC, Chen S. Characterization of Acinetobacter baumannii at a tertiary hospital in Guangzhou: a genomic and clinical study. Microbes Infect 2024; 26:105380. [PMID: 38909679 DOI: 10.1016/j.micinf.2024.105380] [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: 04/02/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/25/2024]
Abstract
Acinetobacter baumannii (AB) infections have become a global public health concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of AB strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.33%) being carbapenem-resistant AB (CRAB), with the main mechanism being the carriage of the blaOXA-23 gene. The overall mortality rate of patients caused by such strains was 15.21% (n = 33). Artificial lung ventilation and the use of meropenem were mortality risk factors in AB-infected patients, while KL2 AB infection was negatively associated. Core genome multilocus sequence typing and clustering analysis were performed on the integrated AB genome collection from the NCBI database and this study to illustrate the population structure among China. The results revealed diverse core genome profiles (n = 17) among AB strains from China, and strains from this single hospital exhibited most of the core genome profiles (n = 13), suggesting genetic variability within the hospital and transmission across the country. These findings show that the high transmission potential of the CRAB strains and meropenem usage that confers a selective advantage of CRAB clinically are two major factors that pose significant challenges to the effective clinical management of AB infections. Understanding the genetic features and transmission patterns of clinical AB strains is crucial for the effective control of infections caused by this pathogen.
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Affiliation(s)
- Heng Heng
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Ling Yang
- Department of Laboratory Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhiwei Zheng
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Chen Yang
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Xuemei Yang
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Wenxing Zhao
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Ruanyang Sun
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Kaichao Chen
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Lianwei Ye
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China
| | - Jun Li
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China
| | - Edward Wai-Chi Chan
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Sheng Chen
- State Key Lab of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China; Shenzhen Key Laboratory of Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China.
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Ding P, Li H, Nan Y, Liu C, Wang G, Cai H, Yu W. Outcome of intravenous and inhaled polymyxin B treatment in patients with multidrug-resistant gram-negative bacterial pneumonia. Int J Antimicrob Agents 2024; 64:107293. [PMID: 39094752 DOI: 10.1016/j.ijantimicag.2024.107293] [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: 05/25/2023] [Revised: 06/26/2024] [Accepted: 07/24/2024] [Indexed: 08/04/2024]
Abstract
PURPOSE The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. METHODS This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. RESULTS Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69-133.78) and 33.82 (0.83-126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were >2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low. CONCLUSIONS Inhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.
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Affiliation(s)
- Peili Ding
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Hangyang Li
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Yuyu Nan
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Chengwei Liu
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Guobin Wang
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Hongliu Cai
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Wenqiao Yu
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
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Shein AMS, Hongsing P, Smith OK, Phattharapornjaroen P, Miyanaga K, Cui L, Ishikawa H, Amarasiri M, Monk PN, Kicic A, Chatsuwan T, Pletzer D, Higgins PG, Abe S, Wannigama DL. Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia. Crit Rev Microbiol 2024:1-22. [PMID: 38949254 DOI: 10.1080/1040841x.2024.2369948] [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: 09/25/2023] [Accepted: 06/11/2024] [Indexed: 07/02/2024]
Abstract
Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.
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Affiliation(s)
- Aye Mya Sithu Shein
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence in, Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Parichart Hongsing
- Mae Fah Luang University Hospital, Chiang Rai, Thailand
- School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, Thailand
| | - O'Rorke Kevin Smith
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Phatthranit Phattharapornjaroen
- Department of Emergency Medicine, Center of Excellence, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Department of Surgery, Sahlgrenska Academy, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden
| | - Kazuhiko Miyanaga
- Division of Bacteriology, School of Medicine, Jichi Medical University, Tochigi, Japan
| | - Longzhu Cui
- Division of Bacteriology, School of Medicine, Jichi Medical University, Tochigi, Japan
| | - Hitoshi Ishikawa
- Yamagata Prefectural University of Health Sciences, Kamiyanagi, Japan
| | - Mohan Amarasiri
- Laboratory of Environmental Hygiene, Department of Health Science, School of Allied Health Sciences, Kitasato University, Kitasato, Sagamihara-Minami, Japan
| | - Peter N Monk
- Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, UK
| | - Anthony Kicic
- Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia, Australia
- Centre for Cell Therapy and Regenerative Medicine, Medical School, The University of Western Australia, Nedlands, Western Australia, Australia
- Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Western Australia, Australia
- School of Population Health, Curtin University, Bentley, Western Australia, Australia
| | - Tanittha Chatsuwan
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence in, Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Daniel Pletzer
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Paul G Higgins
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany
- German Centre for Infection Research, Partner site Bonn-Cologne, Cologne, Germany
- Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Shuichi Abe
- Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Dhammika Leshan Wannigama
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence in, Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
- School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
- Biofilms and Antimicrobial Resistance Consortium of ODA receiving countries, The University of Sheffield, Sheffield, UK
- Pathogen Hunter's Research Team, Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, Japan
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Maan L, Anand N, Yadav G, Mishra M, Gupta MK. The Efficacy and Safety of Intravenous Colistin Plus Aerosolized Colistin Versus Intravenous Colistin Alone in Critically Ill Trauma Patients With Multi-Drug Resistant Gram-Negative Bacilli Infection. Cureus 2023; 15:e49314. [PMID: 38143689 PMCID: PMC10748797 DOI: 10.7759/cureus.49314] [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] [Accepted: 11/22/2023] [Indexed: 12/26/2023] Open
Abstract
BACKGROUND AND AIM Gram-negative bacteria (GNB) with potential multiple drug resistance (MDR) have emerged as a major group of organisms causing ventilator-associated pneumonia (VAP). Higher concentrations are deposited directly in the lungs when antibiotics are given via inhalation, minimizing systemic side effects. This study aims to compare the efficacy and safety of intravenous plus aerosolized colistin versus intravenous (IV) colistin alone in critically ill trauma patients who reported MDR-GNB infection on endotracheal aspirate culture. METHODS A hundred patients were recruited in the Intensive Care Unit, Trauma Centre, Institute of Medical Sciences, Banaras Hindu University, Varanasi, and randomly assigned to the control (n=50) group, which received IV colistin plus aerosolized colistin and the intervention group (n = 50), which received IV colistin alone. Changes in total leucocyte count (TLC), renal function test (RFT), endotracheal aspirate culture, 24-hour urine output, length of ICU stay, and 28-day ICU mortality were investigated. RESULTS Patients receiving intravenous plus nebulized colistin therapy had a better outcome compared to IV colistin alone in terms of faster eradication of MDR-GNB infection. A rise in serum urea and creatinine levels was seen in both groups, which were significantly higher, along with a decrease in urine output in the group receiving intravenous colistin alone. No significant difference was observed in serum sodium and potassium levels in the RFT protocol, length of ICU stay, or 28-day ICU mortality. CONCLUSION Intravenous nebulized colistin could be considered a better alternative therapy for VAP caused by multi-drug-resistant Gram-negative bacteria in the ICU in terms of faster microbiological cure and lesser nephrotoxicity.
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Affiliation(s)
- Loveleen Maan
- Anaesthesiology and Critical Care, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | - Neelesh Anand
- Anaesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varansi, IND
| | - Ghanshyam Yadav
- Anaesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | - Manjaree Mishra
- Anaesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
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Cao B, Cao L. Case Report: A case of spinal muscular atrophy with extensively drug-resistant Acinetobacter baumannii pneumonia treated with nebulization combined with intravenous polymyxin B: experience and a literature review. Front Cell Infect Microbiol 2023; 13:1163341. [PMID: 37415826 PMCID: PMC10321296 DOI: 10.3389/fcimb.2023.1163341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 05/26/2023] [Indexed: 07/08/2023] Open
Abstract
Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive and symmetric muscle weakness and atrophy of the proximal limbs and trunk due to degeneration of spinal alpha-motor neurons. Children are classified into types 1-3, from severe to mild, according to the time of onset and motor ability. Children with type 1 are the most severe, are unable to sit independently, and experience a series of respiratory problems, such as hypoventilation, reduced cough, and sputum congestion. Respiratory failure is easily complicated by respiratory infections and is a major cause of death in children with SMA. Most type 1 children die within 2 years of age. Type 1 children with SMA usually require hospitalization for lower respiratory tract infections and invasive ventilator-assisted ventilation in severe cases. These children are frequently infected with drug-resistant bacteria due to repeated hospitalizations and require long hospital stays requiring invasive ventilation. In this paper, we report a case of nebulization combined with intravenous polymyxin B in a child with spinal muscular atrophy with extensively drug-resistant Acinetobacter baumannii pneumonia, hoping to provide a reference for the treatment of children with extensively drug-resistant Acinetobacter baumannii pneumonia.
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Affiliation(s)
| | - Ling Cao
- Department of Pulmonology, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing, China
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Lu D, Mao W. Efficacy and safety of intravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of multidrug-resistant gram-negative bacterial pneumonia: A systematic review and meta-analysis. Heliyon 2023; 9:e15774. [PMID: 37159708 PMCID: PMC10163663 DOI: 10.1016/j.heliyon.2023.e15774] [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: 02/05/2023] [Revised: 04/18/2023] [Accepted: 04/21/2023] [Indexed: 05/11/2023] Open
Abstract
Background Previous studies have questioned the efficacy and safety of intravenous combined with aerosolised (IV + AS) polymyxin versus intravenous (IV) polymyxin alone in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of IV + AS polymyxin in the treatment of MDR-GNB pneumonia. Methods We identified all relevant studies by searching the PubMed, EMBASE and Cochrane library databases from their inception to May 31, 2022. All included studies were evaluated using the Newcastle Ottawa scale (NOS) checklist. The summary relative risk (RR) and 95% confidence interval (CI) were used to determine the outcome differences between the IV + AS and the IV groups. Subgroup analysis was performed based on population, polymyxin dose and kinds of polymyxin. Results A total of 16 studies were included in the meta-analysis. The IV + AS group had lower mortality (RR = 0.86, 95% CI: 0.77-0.97, P = 0.01) than the IV group. Subgroup analysis revealed that IV + AS polymyxin could reduce mortality only when used in low doses. Simultaneously, the IV + AS group outperformed the IV group in terms of clinical response rate, clinical cure rate, microbiological eradication and duration of mechanical ventilation. The duration of hospitalisation and the incidence of nephrotoxicity did not differ significantly between the two groups. Conclusions IV + AS polymyxin is beneficial in the treatment of MDR-GNB pneumonia. It could lower patient mortality and improve clinical and microbial outcomes without increasing the risk of nephrotoxicity. However, retrospective analysis in the majority of studies and heterogeneity between studies implies that our findings must be interpreted carefully.
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Affiliation(s)
- Difan Lu
- Cardiovascular Ultrasound Center of the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China
| | - Wenchao Mao
- Department of Critical Care Medicine, Zhejiang Hospital, Lingyin Road 12, Hangzhou, 310013, Zhejiang, China
- Corresponding author.
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Shadan A, Pathak A, Ma Y, Pathania R, Singh RP. Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection. Front Cell Infect Microbiol 2023; 13:1053968. [PMID: 36968113 PMCID: PMC10038080 DOI: 10.3389/fcimb.2023.1053968] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infectionAcinetobacter baumannii is a gram-negative multidrug-resistant nosocomial pathogen and a major cause of hospital acquired infetions. Carbapenem resistant A. baumannii has been categorised as a Priority1 critial pathogen by the World Health Organisation. A. baumannii is responsible for infections in hospital settings, clinical sectors, ventilator-associated pneumonia, and bloodstream infections with a mortality rates up to 35%. With the development of advanced genome sequencing, molecular mechanisms of manipulating bacterial genomes, and animal infection studies, it has become more convenient to identify the factors that play a major role in A. baumannii infection and its persistence. In the present review, we have explored the mechanism of infection, virulence factors, and various other factors associated with the pathogenesis of this organism. Additionally, the role of the innate and adaptive immune response, and the current progress in the development of innovative strategies to combat this multidrug-resistant pathogen is also discussed.
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Affiliation(s)
- Afreen Shadan
- Department of Microbiology, Dr. Shyama Prasad Mukherjee University, Ranchi, Jharkhand, India
| | - Avik Pathak
- Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
| | - Ying Ma
- College of Resources and Environment, Southwest University, Chongqing, China
- *Correspondence: Ying Ma, ; Ranjana Pathania, ; Rajnish Prakash Singh,
| | - Ranjana Pathania
- Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee, India
- *Correspondence: Ying Ma, ; Ranjana Pathania, ; Rajnish Prakash Singh,
| | - Rajnish Prakash Singh
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Ranchi, Jharkhand, India
- *Correspondence: Ying Ma, ; Ranjana Pathania, ; Rajnish Prakash Singh,
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11
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Intensification in Genetic Information and Acquisition of Resistant Genes in Genome of Acinetobacter baumannii: A Pan-Genomic Analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3186343. [PMID: 36605106 PMCID: PMC9810410 DOI: 10.1155/2022/3186343] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 11/02/2022] [Accepted: 12/03/2022] [Indexed: 12/29/2022]
Abstract
Acinetobacter baumannii (A. baumannii) attributes 26% of the mortality rate in hospitalized patients, and the percentage can rise to 46 in patients admitted to ICU as it is a major cause of ventilator-associated pneumonia. It has been nominated as the critical priority organism by WHO for which new therapeutic drugs are urgently required. To understand the genomic identification of different strains, antimicrobial resistance patterns, and epidemiological typing of organisms, whole-genome sequencing (WGS) analysis provides insight to explore new epitopes to develop new drugs against the organism. Therefore, the study is aimed at investigating the whole genome sequence of A. baumannii strains to report the new intensifications in its genomic profile. The genome sequences were retrieved from the NCBI database system. Pan-genome BPGA (Bacterial Pan-genome Analysis Tool) was used to analyze the core, pan, and species-specific genome analysis. The pan and core genome curves were extrapolated using the empirical power law equation f(x) = a.xb and the exponential equation f1(x) = c.e (d.x). To identify the resistant genes with resistant mutations against antibiotics, ResFinder and Galaxy Community hub bioinformatics tools were used. According to pan-genome analysis, there were 2227 core genes present in each species of the A. baumannii genome. Furthermore, the number of accessory genes ranged from 1182 to 1460, and the unique genes in the genome were 931. There were 325 exclusively absent genes in the genome of Acinetobacter baumannii. The pan-genome analysis showed that there is a 5-fold increase in the genome of A. baumannii in 5 years, and the genome is still open. There is the addition of multiple unique genes; among them, genes participating in the function of information and processing are increased.
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12
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The prevalence of antibiotic-resistant Acinetobacter baumannii infections among the Iranian ICU patients: A systematic review and meta-analysis. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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13
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Wang JL, Xiang BX, Song XL, Que RM, Zuo XC, Xie YL. Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients: A meta-analysis. World J Clin Cases 2022; 10:11466-11485. [PMID: 36387815 PMCID: PMC9649555 DOI: 10.12998/wjcc.v10.i31.11466] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/15/2022] [Accepted: 09/23/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.
AIM To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit (ICU) patients.
METHODS PubMed, EMBASE, the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30, 2022. The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver. 12.1. Additionally, subgroup analyses and meta-regression were conducted to assess heterogeneity.
RESULTS A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis. The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%. The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B (PMB)-induced nephrotoxicity. The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval, nephrotoxicity criteria, age, publication year, study quality and sample size, which were confirmed in the univariable meta-regression analysis. Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses. Furthermore, older age, the presence of sepsis or septic shock, hypoalbuminemia, and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity, while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity.
CONCLUSION Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high. It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.
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Affiliation(s)
- Jiang-Lin Wang
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Bi-Xiao Xiang
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Xiao-Li Song
- Department of Pharmacy, Sanya Central Hospital, Sanya 572000, Hainan Province, China
| | - Rui-Man Que
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Xiao-Cong Zuo
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Yue-Liang Xie
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
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14
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Chen Y, Li Z, Yin Y, Yang P, Kong Y, Li Z, Chen D, Xu X. Identification of 2-aminothiazoyl piperidine derivatives as a new class of adjuvants potentiating the activity of colistin against Acinetobacter baumannii. CHINESE CHEM LETT 2022. [DOI: 10.1016/j.cclet.2022.107948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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15
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Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis 2022; 75:187-212. [PMID: 35439291 PMCID: PMC9890506 DOI: 10.1093/cid/ciac268] [Citation(s) in RCA: 287] [Impact Index Per Article: 95.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/04/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. The initial guidance document on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa) was published on 17 September 2020. Over the past year, there have been a number of important publications furthering our understanding of the management of ESBL-E, CRE, and DTR-P. aeruginosa infections, prompting a rereview of the literature and this updated guidance document. METHODS A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections reviewed, updated, and expanded previously developed questions and recommendations about the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. RESULTS Preferred and alternative treatment recommendations are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Recommendations apply for both adult and pediatric populations. CONCLUSIONS The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of 24 October 2021. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance/.
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Affiliation(s)
- Pranita D Tamma
- Correspondence: P. D. Tamma, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA ()
| | - Samuel L Aitken
- Department of Pharmacy, University of Michigan Health, Ann Arbor, Michigan, USA
| | - Robert A Bonomo
- Medical Service and Center for Antimicrobial Resistance and Epidemiology, Louis Stokes Cleveland Veterans Affairs Medical Center, University Hospitals Cleveland Medical Center and Departments of Medicine, Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA
| | - Amy J Mathers
- Departments of Medicine and Pathology, University of Virginia, Charlottesville, Virginia, USA
| | - David van Duin
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Cornelius J Clancy
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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16
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Yesil C, Yalcin AN, Ogunc D, Ongut G, Ozhak B, Colak D, Er H, Sarıtas ZE. Use of colistin with rifampicin, trimethoprim-sulfamethoxazole and teicoplanin in acinetobacter mouse infection model. Future Microbiol 2022; 17:665-671. [DOI: 10.2217/fmb-2021-0216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: Infections with multidrug-resistant Gram-negative bacteria such as Acinetobacter baumannii are major cause of morbidity and mortality. Colistin is used commonly to treat these infections. In this study, we evaluated the efficacy of different colistin combinations in a A. baumannii infection mouse model. Materials & methods: An A. baumannii mouse infection model was developed in 150 experimental animals. Treatment groups were as follows: colistin, colistin + rifampicin, colistin + trimethoprim/sulfamethoxazole, colistin + teicoplanin and a control group. The outcome was bacterial burden in the lung and liver tissues. The treatment groups were subdivided into 24-, 48- and 72-h groups. Results: Colistin and combinations reduce the A. baumannii burden significantly in lung and liver tissues compared with the control group. Compared with colistin alone colistin + rifampicin and colistin + TMP-SMX provided significantly better reduction in the bacterial burden. Conclusion: These results may suggest that rifampicin and TMP-SMX combination with colistin may have a potential role in the treatment of A. baumannii infections.
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Affiliation(s)
| | - Ata N Yalcin
- Akdeniz University Medical School, Department of Infectious Diseases & Clinical Microbiology, Antalya, Turkey
| | - Dilara Ogunc
- Akdeniz University Medical School, Department of Medical Microbiology, Antalya, Turkey
| | - Gozde Ongut
- Akdeniz University Medical School, Department of Medical Microbiology, Antalya, Turkey
| | - Betül Ozhak
- Akdeniz University Medical School, Department of Medical Microbiology, Antalya, Turkey
| | - Dilek Colak
- Akdeniz University Medical School, Department of Medical Microbiology, Antalya, Turkey
| | - Halil Er
- University of Health Sciences, Antalya Training & Research Hospital, Department of Medical Microbiology, Antalya, Turkey
| | - Zubeyde E Sarıtas
- University of Health Sciences, Antalya Training & Research Hospital, Department of Medical Microbiology, Antalya, Turkey
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17
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Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Guidance on the Treatment of AmpC β-lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections. Clin Infect Dis 2021; 74:2089-2114. [PMID: 34864936 DOI: 10.1093/cid/ciab1013] [Citation(s) in RCA: 307] [Impact Index Per Article: 76.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. METHODS A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggestions and corresponding rationales. In contrast to guidance in the previous document, published data on optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as "suggested approaches" based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. RESULTS Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. CONCLUSIONS The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of September 17, 2021 and will be updated annually. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.
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Affiliation(s)
- Pranita D Tamma
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Samuel L Aitken
- Department of Pharmacy, University of Michigan Health, Ann Arbor, Michigan, USA
| | - Robert A Bonomo
- Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, University Hospitals Cleveland Medical Center and Departments of Medicine, Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA
| | - Amy J Mathers
- Departments of Medicine and Pathology, University of Virginia, Charlottesville, Virginia, USA
| | - David van Duin
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Cornelius J Clancy
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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18
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Tang R, Luo R. The association between mortality and inhaled antibiotics for ventilator-associated pneumonia: A complex situation-Author's reply. J Crit Care 2021; 67:229. [PMID: 34556385 DOI: 10.1016/j.jcrc.2021.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 09/10/2021] [Indexed: 02/05/2023]
Affiliation(s)
- Rui Tang
- Department of Pharmacy, West China Hospital, Sichuan university, Chengdu, China.
| | - Rui Luo
- Department of Pain Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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19
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Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives. Microorganisms 2021; 9:microorganisms9061154. [PMID: 34072189 PMCID: PMC8227626 DOI: 10.3390/microorganisms9061154] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 05/14/2021] [Accepted: 05/20/2021] [Indexed: 11/17/2022] Open
Abstract
Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20-25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.
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20
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Almangour TA, Garcia E, Zhou Q, Forrest A, Kaye KS, Li J, Velkov T, Rao GG. Polymyxins for the treatment of lower respiratory tract infections: lessons learned from the integration of clinical pharmacokinetic studies and clinical outcomes. Int J Antimicrob Agents 2021; 57:106328. [PMID: 33785362 DOI: 10.1016/j.ijantimicag.2021.106328] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 02/18/2021] [Accepted: 03/20/2021] [Indexed: 11/26/2022]
Abstract
The global rise in nosocomial pneumonia caused by multidrug-resistant (MDR) Gram-negative pathogens and the increasingly limited antibiotic treatment options are growing threats to modern medicine. As a result, older antibiotics such as polymyxins are being used as last-resort drugs for MDR nosocomial pneumonia. Polymyxins are bactericidal against most aerobic Gram-negative bacilli. High-dose intravenous (IV) adminsitration of polymyxins, however, results in subtherapeutic concentrations at the site of infection making treatment challenging. Alternative forms of polymyxin delivery have been considered in order to better achieve the necessary concentrations at the site of infection. Several studies have evaluated the effectiveness of aerosolised polymyxins in patients with nosocomial pneumonia caused by MDR Gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Here we evaluated the pharmacokinetic data supporting the use of inhaled polymyxins in nosocomial pneumonia and provide insight into the limitations and challenges that future studies should address. We have also reviewed the literature published between 2006 and 2020 on the use of aerosolised polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, in patients without cystic fibrosis to evaluate their safety and efficacy as monotherapy or as an adjunct to IV antimicrobials. This review highlights the need for well-designed multicentre studies with standardised methodologies to further evaluate the effectiveness of inhaled polymyxins and to provide reliable pharmacokinetic/pharmacodynamic data in order to redefine appropriate dosing strategies.
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Affiliation(s)
- Thamer A Almangour
- Department of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Estefany Garcia
- Department of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA
| | - Qi Zhou
- Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA
| | - Alan Forrest
- Department of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA
| | - Keith S Kaye
- Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Jian Li
- Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, Victoria, Australia
| | - Tony Velkov
- Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Victoria, Australia
| | - Gauri G Rao
- Department of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA.
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21
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Wagenlehner F, Lucenteforte E, Pea F, Soriano A, Tavoschi L, Steele VR, Henriksen AS, Longshaw C, Manissero D, Pecini R, Pogue JM. Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins. Clin Microbiol Infect 2021; 27:S1198-743X(20)30764-3. [PMID: 33359542 DOI: 10.1016/j.cmi.2020.12.009] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 11/03/2020] [Accepted: 12/10/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Nephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria with limited therapeutic options has resulted in increased use of polymyxins. OBJECTIVES To determine the rates of nephrotoxicity and neurotoxicity during polymyxin treatment and whether any factors influence these. DATA SOURCES Medline, Embase and Cochrane Library databases were searched on 2 January 2020. STUDY ELIGIBILITY CRITERIA Studies reporting nephrotoxicity and/or neurotoxicity rates in patients with infections treated with polymyxins were included. Reviews, meta-analyses and reports not in English were excluded. PARTICIPANTS Patients hospitalized with infections treated with systemic or inhaled polymyxins were included. For comparative analyses, patients treated with non-polymyxin-based regimens were also included. METHODS Meta-analyses were performed using a random-effects model; subgroup meta-analyses were conducted where data permitted using a mixed-effects model. RESULTS In total, 237 reports of randomized controlled trials, cohort and case-control studies were eligible for inclusion; most were single-arm observational studies. Nephrotoxic events in 35,569 patients receiving polymyxins were analysed. Overall nephrotoxicity rate was 0.282 (95% confidence interval (CI) 0.259-0.307). When excluding studies where >50% of patients received inhaled-only polymyxin treatment or nephrotoxicity assessment was by methods other than internationally recognized criteria (RIFLE, KDIGO or AKIN), the nephrotoxicity rate was 0.391 (95% CI 0.364-0.419). The odds of nephrotoxicity were greater with polymyxin therapies compared to non-polymyxin-based regimens (odds ratio 2.23 (95% CI 1.58-3.15); p < 0.001). Meta-analyses showed a significant effect of polymyxin type, dose, patient age, number of concomitant nephrotoxins and use of diuretics, glycopeptides or vasopressors on the rate of nephrotoxicity. Polymyxin therapies were not associated with a significantly different rate of neurotoxicity than non-polymyxin-based regimens (p 0.051). The overall rate of neurotoxicity during polymyxin therapy was 0.030 (95% CI 0.020-0.043). CONCLUSIONS Polymyxins are associated with a higher risk of nephrotoxicity than non-polymyxin-based regimens.
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Affiliation(s)
- Florian Wagenlehner
- Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany
| | - Ersilia Lucenteforte
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Federico Pea
- Department of Medicine, University of Udine and Institute of Clinical Pharmacology, SM Misericordia University Hospital, ASUIUD, Udine, Italy
| | - Alex Soriano
- Infectious Diseases Department, Hospital Clínic of Barcelona, University of Barcelona IDIBAPS, Barcelona, Spain
| | - Lara Tavoschi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | | | | | - Davide Manissero
- University College of London, Institute for Global Health, London, UK
| | | | - Jason M Pogue
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
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22
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Choe J, Sohn YM, Jeong SH, Park HJ, Na SJ, Huh K, Suh GY, Jeon K. Inhalation with intravenous loading dose of colistin in critically ill patients with pneumonia caused by carbapenem-resistant gram-negative bacteria. Ther Adv Respir Dis 2020; 13:1753466619885529. [PMID: 31680646 PMCID: PMC6852352 DOI: 10.1177/1753466619885529] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Despite the increasing use of colistin in clinical practice, the optimal
dosing, and administration route have not been established. This study aimed
to evaluate the clinical outcome and safety of intravenous (IV) colistin
with a loading dose (LD) and adjunctive aerosolized (AS) colistin
administration in critically ill patients with hospital-acquired pneumonia
(HAP) or ventilator-associated pneumonia (VAP) caused by
carbapenem-resistant gram-negative bacteria (CRGNB). Methods: We retrospectively reviewed 191 critically ill patients who received colistin
for the treatment of HAP or VAP caused by CRGNB. Patients were divided into
three groups: non-LD IV (patients received only IV colistin without LD), LD
IV (patients received only IV colistin with LD), and AS–LD (patients
received IV colistin with LD and adjunctive AS colistin). Results: There was no difference in clinical response between the three groups.
However, the rate of microbiological eradication was significantly higher in
the AS–LD group (60%) than in the non-LD IV (31%), and LD IV (33%) groups
(p = 0.010). Patients treated with adjunctive AS
colistin in combination with LD IV had significantly lower 30-day mortality
rates than patients treated with IV colistin alone
(p = 0.027). After adjusting for potential confounding
factors, adjunctive AS colistin was still significantly associated with
lower mortality (adjusted OR 0.338, CI 95% 0.132–0.864,
p = 0.024). However, nephrotoxicity did not change
according to the use of LD regimen and AS colistin administration
(p = 0.100). Conclusions: Adjunctive AS colistin in combination with IV colistin with LD was related to
an improved 30-day mortality and microbiological outcome without an increase
in nephrotoxicity in critically ill patients with HAP and VAP caused by
CRGNB. The reviews of this paper are available via the supplemental
material section.
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Affiliation(s)
- Junsu Choe
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - You Min Sohn
- Department of Pharmaceutical Services, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Suk Hyeon Jeong
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyo Jung Park
- Department of Pharmaceutical Services, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Soo Jin Na
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyungmin Huh
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gee Young Suh
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyeongman Jeon
- Department of Critical Care Medicine and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
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23
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Deng W, Fu T, Zhang Z, Jiang X, Xie J, Sun H, Hu P, Ren H, Zhou P, Liu Q, Long Q. L-lysine potentiates aminoglycosides against Acinetobacter baumannii via regulation of proton motive force and antibiotics uptake. Emerg Microbes Infect 2020; 9:639-650. [PMID: 32192413 PMCID: PMC7144275 DOI: 10.1080/22221751.2020.1740611] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 03/02/2020] [Accepted: 03/05/2020] [Indexed: 11/09/2022]
Abstract
Acinetobacter baumannii, a Gram-negative opportunistic pathogen, is a leading cause of hospital- and community-acquired infections. Acinetobacter baumannii can rapidly acquire diverse resistance mechanisms and undergo genetic modifications that confer resistance and persistence to all currently used clinical antibiotics. In this study, we found exogenous L-lysine sensitizes Acinetobacter baumannii, other Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) and a Gram-positive bacterium (Mycobacterium smegmatis) to aminoglycosides. Importantly, the combination of L-lysine with aminoglycosides killed clinically isolated multidrug-resistant Acinetobacter baumannii and persister cells. The exogenous L-lysine can increase proton motive force via transmembrane chemical gradient, resulting in aminoglycoside acumination that further accounts for reactive oxygen species production. The combination of L-lysine and antibiotics highlights a promising strategy against bacterial infection.
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Affiliation(s)
- Wanyan Deng
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
| | - Tiwei Fu
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Zhen Zhang
- Department of Clinical Laboratory, Chongqing General Hospital, Chongqing, People’s Republic of China
| | - Xiao Jiang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
| | - Jianping Xie
- State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, People’s Republic of China
| | - Hang Sun
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
| | - Peng Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
| | - Hong Ren
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
| | - Peifu Zhou
- School of Ethnic-Minority Medicine, Guizhou Minzu University, Guizhou, People’s Republic of China
| | - Qi Liu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
| | - Quanxin Long
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR People’s Republic of China
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24
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Nasr P. Genetics, epidemiology, and clinical manifestations of multidrug-resistant Acinetobacter baumannii. J Hosp Infect 2020; 104:4-11. [DOI: 10.1016/j.jhin.2019.09.021] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 09/26/2019] [Accepted: 09/27/2019] [Indexed: 11/24/2022]
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25
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A Breath of Fresh Air in the Fog of Antimicrobial Resistance: Inhaled Polymyxins for Gram-Negative Pneumonia. Antibiotics (Basel) 2019; 8:antibiotics8010027. [PMID: 30884839 PMCID: PMC6466860 DOI: 10.3390/antibiotics8010027] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 03/08/2019] [Accepted: 03/12/2019] [Indexed: 01/08/2023] Open
Abstract
Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the use of inhaled antibiotics to rapidly achieve therapeutic concentrations directly at the site of infection. In particular, there is significant interest in the role of inhaled polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, due to their retained activity against multi-drug resistant Gram-negative pathogens, including Acinetobacter baumannii and Pseudomonas aeruginosa. This review will provide a comprehensive overview of the pharmacokinetic/pharmacodynamic profile, clinical outcomes, safety, and potential role of inhaled polymyxins in clinical practice.
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26
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Nation RL, Forrest A. Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Polymyxins: Implications for Therapeutic Use. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1145:219-249. [PMID: 31364081 DOI: 10.1007/978-3-030-16373-0_15] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The availability of sensitive, accurate and specific analytical methods for the measurement of polymyxins in biological fluids has enabled an understanding of the pharmacokinetics of these important antibiotics in healthy humans and patients. Colistin is administered as its inactive prodrug colistin methanesulfonate (CMS) and has especially complex pharmacokinetics. CMS undergoes conversion in vivo to the active entity colistin, but the rate of conversion varies from brand to brand and possibly from batch to batch. The extent of conversion is generally quite low and depends on the relative magnitudes of the conversion clearance and other clearance pathways for CMS of which renal excretion is a major component. Formed colistin in the systemic circulation undergoes very extensive tubular reabsorption; the same mechanism operates for polymyxin B which is administered in its active form. The extensive renal tubular reabsorption undoubtedly contributes to the propensity for the polymyxins to cause nephrotoxicity. While there are some aspects of pharmacokinetic behaviour that are similar between the two clinically used polymyxins, there are also substantial differences. In this chapter, the pharmacokinetics of colistin, administered as CMS, and polymyxin B are reviewed, and the therapeutic implications are discussed.
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Affiliation(s)
- Roger L Nation
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
| | - Alan Forrest
- Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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27
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Asif M, Alvi IA, Rehman SU. Insight into Acinetobacter baumannii: pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities. Infect Drug Resist 2018; 11:1249-1260. [PMID: 30174448 PMCID: PMC6110297 DOI: 10.2147/idr.s166750] [Citation(s) in RCA: 183] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Acinetobacter baumannii, once considered a low-category pathogen, has emerged as an obstinate infectious agent. The scientific community is paying more attention to this pathogen due to its stubbornness to last resort antimicrobials, including carbapenems, colistin, and tigecycline, its high prevalence of infections in the hospital setting, and significantly increased rate of community-acquired infections by this organism over the past decade. It has given the fear of pre-antibiotic era to the world. To further enhance our understanding about this pathogen, in this review, we discuss its taxonomy, pathogenesis, current treatment options, global resistance rates, mechanisms of its resistance against various groups of antimicrobials, and future therapeutics.
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Affiliation(s)
- Muhammad Asif
- Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan,
- Department of Pathology, King Edward Medical University, Lahore, Pakistan
| | - Iqbal Ahmad Alvi
- Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan,
- Department of Microbiology, Hazara University, Mansehra, Pakistan
| | - Shafiq Ur Rehman
- Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan,
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28
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Vardakas KZ, Mavroudis AD, Georgiou M, Falagas ME. Intravenous plus inhaled versus intravenous colistin monotherapy for lower respiratory tract infections: A systematic review and meta-analysis. J Infect 2018; 76:321-327. [PMID: 29428226 DOI: 10.1016/j.jinf.2018.02.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 02/03/2018] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To evaluate whether intravenous plus inhaled combination (IV/INHCC) compared to intravenous monotherapy (IVCM) was associated with patient outcomes and identify factors influencing study outcomes. METHODS PubMed and Scopus were searched till November 2016. Studies were included if they evaluated adult patients with lower respiratory tract infections due to MDR/XDR Gram-negative bacteria and reported comparative mortality data (adjusted and unadjusted) for patients receiving IV/INHCC versus IVCM. Random effects meta-analyses were performed. RESULTS Thirteen studies (11 retrospective, 2 prospective) were included. The overall quality of data was low to very low and characterized by the lack of adjusted data. The majority of the studies were designed to evaluate the outcome of the meta-analysis. Both IV and inhaled colistin were administered at variable doses. There was no difference in mortality between IV/INHCC and IVCM when all studies were combined (13 studies, 1115 patients, risk ratio 0.94, 95% confidence interval 0.81-1.08). Only the analysis that included studies with low-dose IV colistin showed significant difference in favor of IV/INHCC versus IVCM (0.65, 0.45-0.94). CONCLUSIONS Overall, low quality data suggest that IV/INHCC did not lower mortality in patients with MDR Gram negative infections unless low IV colistin dose was administered.
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Affiliation(s)
- Konstantinos Z Vardakas
- Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Medicine, Henry Dunant Hospital Center, Athens, Greece
| | | | | | - Matthew E Falagas
- Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Medicine, Henry Dunant Hospital Center, Athens, Greece; Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
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29
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Jung SY, Lee SH, Lee SY, Yang S, Noh H, Chung EK, Lee JI. Antimicrobials for the treatment of drug-resistant Acinetobacter baumannii pneumonia in critically ill patients: a systemic review and Bayesian network meta-analysis. Crit Care 2017; 21:319. [PMID: 29262831 PMCID: PMC5738897 DOI: 10.1186/s13054-017-1916-6] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 12/04/2017] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND An optimal therapy for the treatment of pneumonia caused by drug-resistant Acinetobacter baumannii remains unclear. This study aims to compare various antimicrobial strategies and to determine the most effective therapy for pneumonia using a network meta-analysis. METHODS Systematic search and quality assessment were performed to select eligible studies reporting one of the following outcomes: all-cause mortality, clinical cure, and microbiological eradication. The primary outcome was all-cause mortality. A network meta-analysis was conducted with a Bayesian approach. Antimicrobial treatments were ranked based on surface under the cumulative ranking curve (SUCRA) value along with estimated median outcome rate and corresponding 95% credible intervals (CrIs). Two treatments were considered significantly different if a posterior probability of superiority (P) was greater than 97.5%. RESULTS Twenty-three studies evaluating 15 antimicrobial treatments were included. Intravenous colistin monotherapy (IV COL) was selected as a common comparator, serving as a bridge for developing the network. Five treatments ranked higher than IV COL (SUCRA, 57.1%; median all-cause mortality 0.45, 95% CrI 0.41-0.48) for reducing all-cause mortality: sulbactam monotherapy (SUL, 100.0%; 0.18, 0.04-0.42), high-dose SUL (HD SUL, 85.7%; 0.31, 0.07-0.71), fosfomycin plus IV COL (FOS + IV COL, 78.6%; 0.34, 0.19-0.54), inhaled COL plus IV COL (IH COL + IV COL, 71.4%; 0.39, 0.32-0.46), and high-dose tigecycline (HD TIG, 71.4%; 0.39, 0.16-0.67). Those five treatments also ranked higher than IV COL (SUCRA, 45.5%) for improving clinical cure (72.7%, 72.7%, 63.6%, 81.8%, and 90.9%, respectively). Among the five treatments, SUL (P = 98.1%) and IH COL + IV COL (P = 99.9%) were significantly superior to IV COL for patient survival and clinical cure, respectively. In terms of microbiological eradication, FOS + IV COL (P = 99.8%) and SUL (P = 98.9%) were significantly superior to IV COL. CONCLUSIONS This Bayesian network meta-analysis demonstrated the comparative effectiveness of fifteen antimicrobial treatments for drug-resistant A. baumannii pneumonia in critically ill patients. For survival benefit, SUL appears to be the best treatment followed by HD SUL, FOS + IV COL, IH COL + IV COL, HD TIG, and IV COL therapy, in numerical order.
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Affiliation(s)
- Su Young Jung
- Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826 Republic of Korea
- Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Seung Hee Lee
- Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826 Republic of Korea
| | - Soo Young Lee
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
- Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Seungwon Yang
- Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Hayeon Noh
- Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Eun Kyoung Chung
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Jangik I. Lee
- Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826 Republic of Korea
- Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
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30
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Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges. Clin Microbiol Rev 2017; 30:409-447. [PMID: 27974412 DOI: 10.1128/cmr.00058-16] [Citation(s) in RCA: 723] [Impact Index Per Article: 90.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.
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31
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Wood GC, Swanson JM. An Update on Aerosolized Antibiotics for Treating Hospital-Acquired and Ventilator-Associated Pneumonia in Adults. Ann Pharmacother 2017; 51:1112-1121. [PMID: 28778127 DOI: 10.1177/1060028017723934] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE A significant percentage of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have poor outcomes with intravenous antibiotics. It is not clear if adding aerosolized antibiotics improves treatment. This review is an update on using aerosolized antibiotics for treating HAP/VAP in adults. DATA SOURCES PubMed search using the terms "aerosolized antibiotics pneumonia," "nebulized antibiotics pneumonia," and "inhaled antibiotics pneumonia." Reference lists from identified articles were also searched. STUDY SELECTION AND DATA EXTRACTION Clinical studies of aerosolized antibiotics for treating HAP/VAP in adults from July 2010 to March 2017. This article updates a previous review on this topic written in mid-2010. DATA SYNTHESIS The size and quality of studies have improved dramatically in the recent time period compared to previous studies. However, there still are not large randomized controlled trials available. Colistin and aminoglycosides were the most commonly studied agents, and the most common pathogens were Pseudomonas and Acinetobacter. The clinical efficacy of adding aerosolized antibiotics was mixed. Approximately half of the studies showed better outcomes, and none showed worse outcomes. Aerosolized antibiotics appear to be relatively safe, though pulmonary adverse events can occur. Attention to proper administration technique in mechanically ventilated patients is required, including the use of vibrating plate nebulizers. CONCLUSIONS Adding aerosolized antibiotics to intravenous antibiotics may improve the outcomes of adult patients with HAP/VAP in some settings. It seems reasonable to add aerosolized antibiotics in patients with multidrug-resistant organisms or who appear to be failing therapy. Clinicians should pay attention to potential adverse events and proper administration technique.
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Affiliation(s)
| | - Joseph M Swanson
- 1 University of Tennessee Health Science Center, Memphis, TN, USA
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32
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In Vitro Activity of Colistin and Trimethoprim/Sulfamethoxazole Against Consortia of Multidrug Resistant Non-Fermenting Gram-Negative Bacilli Isolated from Lower Respiratory Tract. Jundishapur J Microbiol 2017. [DOI: 10.5812/jjm.43081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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33
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In Vitro Activity of Colistin and Trimethoprim/Sulfamethoxazole Against Consortia of Multidrug Resistant Non-Fermenting Gram-Negative Bacilli Isolated from Lower Respiratory Tract. Jundishapur J Microbiol 2017. [DOI: 10.5812/jjm.14034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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34
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Verma P, Tiwari M, Tiwari V. In silico high-throughput virtual screening and molecular dynamics simulation study to identify inhibitor for AdeABC efflux pump of Acinetobacter baumannii. J Biomol Struct Dyn 2017; 36:1182-1194. [PMID: 28393677 DOI: 10.1080/07391102.2017.1317025] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Emergence of multi-drug resistant strains of Acinetobacter baumannii has caused significant health problems and is responsible for high morbidity and mortality. Overexpression of AdeABC efflux system is one of the major mechanisms. In this study, we have focused on overcoming the drug resistance by identifying inhibitors that can effectively bind and inhibit integral membrane protein, AdeB of this efflux pump. We performed homology modeling to generate structure of AdeB using MODELLER v9.16 followed by model refinement using 3D-Refine tool and validated using PSVS, ProsaWeb, ERRAT, etc. The energy minimization of modeled protein was done using Protein preparation wizard application included in Schrodinger suite. High-throughput virtual screening of 159,868 medicinal compounds against AdeB was performed using three sequential docking modes (i.e. HTVS, SP and XP). Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was done using QIKPROP. The selected 123 compounds were further analyzed for binding free energy by molecular mechanics (using prime MM-GBSA). We have also performed enrichment study (ROC curve analysis) to validate our docking results. The selected molecule and its interaction with AdeB were validated by molecular dynamics simulation (MDS) using GROMACS v5.1.4. In silico high-throughput virtual screening and MDS validation identified ZINC01155930 ((4R)-3-(cycloheptoxycarbonyl)-4-(4-etochromen-3-yl)-2-methyl-4,6,7,8-tetrahydroquinolin-5-olate) as a possible inhibitor for AdeB. Hence, it might be a suitable efflux pump inhibitor worthy of further investigation in order to be used for controlling infections caused by Acinetobacter baumannii.
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Affiliation(s)
- Privita Verma
- a Department of Biochemistry , Central University of Rajasthan , Bandarsindri, Ajmer 305817 , India
| | - Monalisa Tiwari
- a Department of Biochemistry , Central University of Rajasthan , Bandarsindri, Ajmer 305817 , India
| | - Vishvanath Tiwari
- a Department of Biochemistry , Central University of Rajasthan , Bandarsindri, Ajmer 305817 , India
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35
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Early Replacement of Conventional Endotracheal Tube with Endotracheal Tube with Subglottic Suction port for the New Intensive Care Patients; Preventive or Problematic against Ventilator Associated Events? JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2016. [DOI: 10.22207/jpam.10.4.23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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36
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Schreiber MP, Shorr AF. Challenges and opportunities in the treatment of ventilator-associated pneumonia. Expert Rev Anti Infect Ther 2016; 15:23-32. [DOI: 10.1080/14787210.2017.1250625] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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