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Long WM, Xu WX, Hu Q, Qu Q, Wu XL, Chen Y, Wan Q, Xu TT, Luo Y, Qu J. The efficacy and safety of ceftazidime/avibactam or polymyxin B based regimens for carbapenem-resistant Pseudomonas aeruginosa infection: a multicenter real-world and propensity score-matched study. Front Pharmacol 2025; 16:1533952. [PMID: 40230702 PMCID: PMC11994704 DOI: 10.3389/fphar.2025.1533952] [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: 12/09/2024] [Accepted: 03/20/2025] [Indexed: 04/16/2025] Open
Abstract
Introduction Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections pose a critical clinical challenge. Although ceftazidime/avibactam (CAZ/AVI) and polymyxin B (PMB) are frontline therapies, their comparative effectiveness in terms of 30-day survival, renal safety profiles, and clinical success rates remains poorly characterized. To address this knowledge gap, a multicenter real-world study was conducted. Methods CRPA-infected patients treated with PMB or CAZ/AVI-based regimens were enrolled from five hospitals between January 1, 2021, to July 31, 2023. Propensity score matching (PSM) and binary logistic regression analysis were performed to evaluate efficacy and acute renal injury (AKI) occurrence, and a multivariable COX proportional hazards regression of the 30-day all-cause mortality was performed. Results 170 CRPA-infected patients were enrolled, among whom 124 (72.9%) had difficult-to-treat resistant P. aeruginosa (DTR-PA) infections and 77 (45.3%) received CAZ/AVI-based regimens. After 1:1 PSM, the results demonstrated that the CRPA clearance rate was significantly higher in the CAZ/AVI group compared to the PMB group (61.0% vs. 24.4%, p = 0.001); however, no significant differences were observed in clinical success rates (55.6% vs. 44.4%), incidence of AKI (26.8% vs. 39.0%), or 30-day all-cause mortality (7.3% vs. 12.2%) between the two groups (all p > 0.05). Compared with the PMB-based regimens, CAZ/AVI-based regimens were significantly associated with CRPA clearance success (OR 0.185, 95%CI 0.061-0.564, p < 0.001); additionally, multi-site infection (OR 0.295, 95%CI 0.097-0.899, p = 0.032) and the number of combined anti-PA antibiotics (OR 0.435, 95%CI 0.213-0.888, p = 0.022) were associated with enhanced CRPA clearance. The occurrence of AKI in patients with CRPA infection was associated with underlying diseases, including sepsis/septic shock (OR 3.405, 95%CI 1.007-11.520, p = 0.049), and diabetes mellitus (OR 3.600, 95%CI 1.018-12.733, p = 0.047). In addition, other CREs infection (HR 40.849, 95%CI 3.323-502.170, p = 0.004), APACHE II score (HR 1.072, 95%CI 1.032-1.114, p < 0.001) were found to be independent predictors of 30-day all-cause mortality. Conclusion In conclusion, CAZ/AVI-based regimens demonstrated superior efficacy in clearing CRPA compared to PMB-based regimens. Furthermore, several factors associated with AKI and mortality in CRPA-infected patients were identified, highlighting the need for further research to optimize treatment strategies.
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Affiliation(s)
- Wen-Ming Long
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, Changsha, China
- Department of Pharmacy, The Second People’s Hospital of Huaihua City (The Central Hospital of Huaihua City), Huaihua, China
| | - Wei-Xin Xu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Qin Hu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Qiang Qu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Xiao-Li Wu
- Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Ying Chen
- Department of Pharmacy, Renmin Hospital, Wuhan University, Wuhan, China
| | - Qing Wan
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tian-Tian Xu
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yue Luo
- Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, China
| | - Jian Qu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, Changsha, China
- Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China
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Yan A, Pan X, Li S, Hu Y, Zhang H, Li D, Huang L. Polymyxin B in The Treatment of Infections Caused by Multidrug-Resistant Gram-Negative Bacteria in Children: A Retrospective Case Series and A Literature Review. Infect Drug Resist 2025; 18:965-977. [PMID: 39990784 PMCID: PMC11846531 DOI: 10.2147/idr.s509782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 01/25/2025] [Indexed: 02/25/2025] Open
Abstract
Background Multidrug-resistant Gram-negative bacteria (MRGN) pose a significant threat and require priority attention. Polymyxin B (PMB) retains substantial activity against MRGN and makes it potentially the last resort therapy for MRGN infections in children. To assess the effectiveness and safety of PMB in treating MRGN infections in Chinese children. Methods Paediatric patients aged 0-18 years who were treated with PMB for MRGN infections were enrolled in the study. These cases were then compared with those identified in a literature review. In logistic regression, three independent variables were used for analyzing clinical effectiveness, and two for nephrotoxicity. Results A cohort of 54 children was included in study and 24 eligible literature of 259 children were included in literature review. Out of the 54 patients, 53.7% showed favorable clinical responses, while 13.0% died during their hospitalization, of which 3.7% died within 30 days after receiving PMB. AKI was observed in 25.9% patients with 11.1% risk stage, 7.4% injury stage and 7.4% failure stage. The PMB co-administration with carbapenems was associated with significantly higher effectiveness (odds rate [OR] = 3.16, 95% confidence interval [CI]: 1.02-9.86, P = 0.05) and co-administration with potent diuretic (furosemide) may increase the risk of AKI (OR = 4.91, 95% CI: 0.96-24.98, P = 0.05). Conclusion PMB has advantages in treating MRGN infections in paediatric patients, showing favorable clinical responses and pathogen clearance. AKI is a notable safety concern. The small sample size might hinder reliable identification of factors affecting clinical effectiveness and adverse effects.
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Affiliation(s)
- Aihua Yan
- Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Pharmaceutical Preparation Section, Children’s Hospital of Kunming Medical University, Kunming, People’s Republic of China
| | - Xiangcheng Pan
- Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, People’s Republic of China
| | - Siyu Li
- Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Yaxin Hu
- West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China
| | - Haiyang Zhang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Deyuan Li
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Liang Huang
- Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, People’s Republic of China
- West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China
- Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Sichuan University, Chengdu, People’s Republic of China
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Zhuang HH, Qu Q, Long WM, Hu Q, Wu XL, Chen Y, Wan Q, Xu TT, Luo Y, Yuan HY, Lu Q, Qu J. Ceftazidime/avibactam versus polymyxin B in carbapenem-resistant Klebsiella pneumoniae infections: a propensity score-matched multicenter real-world study. Infection 2025; 53:95-106. [PMID: 38884857 PMCID: PMC11825550 DOI: 10.1007/s15010-024-02324-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/10/2024] [Indexed: 06/18/2024]
Abstract
OBJECTIVES In this retrospective observational multicenter study, we aimed to assess efficacy and mortality between ceftazidime/avibactam (CAZ/AVI) or polymyxin B (PMB)-based regimens for the treatment of Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, as well as identify potential risk factors. METHODS A total of 276 CRKP-infected patients were enrolled in our study. Binary logistic and Cox regression analysis with a propensity score-matched (PSM) model were performed to identify risk factors for efficacy and mortality. RESULTS The patient cohort was divided into PMB-based regimen group (n = 98, 35.5%) and CAZ/AVI-based regimen group (n = 178, 64.5%). Compared to the PMB group, the CAZ/AVI group exhibited significantly higher rates of clinical efficacy (71.3% vs. 56.1%; p = 0.011), microbiological clearance (74.7% vs. 41.4%; p < 0.001), and a lower incidence of acute kidney injury (AKI) (13.5% vs. 33.7%; p < 0.001). Binary logistic regression revealed that the treatment duration independently influenced both clinical efficacy and microbiological clearance. Vasoactive drugs, sepsis/septic shock, APACHE II score, and treatment duration were identified as risk factors associated with 30-day all-cause mortality. The CAZ/AVI-based regimen was an independent factor for good clinical efficacy, microbiological clearance, and lower AKI incidence. CONCLUSIONS For patients with CRKP infection, the CAZ/AVI-based regimen was superior to the PMB-based regimen.
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Affiliation(s)
- Hai-Hui Zhuang
- Department of Pharmacy, the Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Central South University, No.139 Middle Renmin Road, Changsha, 410011, China
| | - Qiang Qu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, China
- Institute of Hospital Management, Central South University, Changsha, 410078, China
| | - Wen-Ming Long
- Department of Pharmacy, Second People's Hospital of Huaihua City (The Central Hospital of Huaihua City), Jingzhou District, Huaihua, 418400, China
| | - Qin Hu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, China
- Institute of Hospital Management, Central South University, Changsha, 410078, China
| | - Xiao-Li Wu
- Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
| | - Ying Chen
- Department of Pharmacy, Renmin Hospital, Wuhan University, Wuhan, 430060, China
| | - Qing Wan
- Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Tian-Tian Xu
- Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Yue Luo
- Department of Pharmacy, The People's Hospital of Liuyang, Liuyang, 410300, China
| | - Hai-Yan Yuan
- Department of Pharmacy, the Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Central South University, No.139 Middle Renmin Road, Changsha, 410011, China
| | - Qiong Lu
- Department of Pharmacy, the Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Central South University, No.139 Middle Renmin Road, Changsha, 410011, China
| | - Jian Qu
- Department of Pharmacy, the Second Xiangya Hospital, Institute of Clinical Pharmacy, Central South University, Central South University, No.139 Middle Renmin Road, Changsha, 410011, China.
- Changsha Medical University, Changsha, 410219, China.
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Chen J, Xia B, Liu Y, Sun W, Liu F, Pang J, Cheng H. Clinical outcomes and safety of polymyxin B versus tigecycline combination therapy for pneumonia of carbapenem-resistant Klebsiella pneumoniae: a retrospective cohort study. Ann Med 2024; 56:2397087. [PMID: 39239861 PMCID: PMC11382689 DOI: 10.1080/07853890.2024.2397087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/08/2024] [Accepted: 07/23/2024] [Indexed: 09/07/2024] Open
Abstract
PURPOSE Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality. METHODS This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury. RESULTS Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B (p < 0.05). CONCLUSIONS Polymyxin B-based combination therapy at the standard dose should be used with caution for patients with CRKP-induced pneumonia, especially for men who used carbapenems prior to CRKP detection.
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Affiliation(s)
- Jing Chen
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Binbin Xia
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Yang Liu
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Wenfang Sun
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Fang Liu
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Jingyao Pang
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Hua Cheng
- Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
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Song MH, Xiang BX, Yang CY, Lee CH, Yan YX, Yang QJ, Yin WJ, Zhou Y, Zuo XC, Xie YL. A pilot clinical risk model to predict polymyxin-induced nephrotoxicity: a real-world, retrospective cohort study. J Antimicrob Chemother 2024; 79:1919-1928. [PMID: 38946304 DOI: 10.1093/jac/dkae185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/21/2024] [Indexed: 07/02/2024] Open
Abstract
OBJECTIVES Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN. METHODS Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model. RESULTS Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696-0.787) for internal validation, of 0.708 (95% CI: 0.605-0.810) for temporal validation and of 0.874 (95% CI: 0.759-0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from -3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%. CONCLUSIONS This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%.
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Affiliation(s)
- Mong-Hsiu Song
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China
| | - Bi-Xiao Xiang
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
- College of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563003, China
| | - Chien-Yi Yang
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China
| | - Chou-Hsi Lee
- Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China
| | - Yu-Xuan Yan
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China
| | - Qin-Jie Yang
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
| | - Wen-Jun Yin
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
- Department of Pharmacy and Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
| | - Yangang Zhou
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
| | - Xiao-Cong Zuo
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
- Department of Pharmacy and Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
| | - Yue-Liang Xie
- Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China
- Department of Pharmacy and Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
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Wang J, Li Y, Huang S, Wang M, Jin L, Luo X, Cheng X, Yang N, Zhu H. Mid-dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients. CPT Pharmacometrics Syst Pharmacol 2023; 12:1911-1921. [PMID: 37655610 PMCID: PMC10725268 DOI: 10.1002/psp4.13040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 08/10/2023] [Accepted: 08/21/2023] [Indexed: 09/02/2023] Open
Abstract
This study aimed to evaluate the association between polymyxin B (PMB) exposure and acute kidney injury (AKI) and analyze the risk factors for PMB-induced AKI in critically ill patients. Plasma concentrations of PMB were determined using an ultraperformance liquid chromatography-tandem mass spectrometer in intensive care unit patients who were administered PMB. Univariate and multivariate analyses were conducted to identify risk factors. A receiver operating characteristic curve was constructed to assess the discriminant power of the factors and to identify the cutoff value for AKI. The white blood cell count and estimated area under the concentration-time curve (AUC) of patients administered PMB were independent risk factors for PMB-induced AKI, where AUC were calculated using a first-order pharmacokinetic equation based on the mid-dosing interval concentration (C1/2t ) and peak concentration. The area under the receiver operating characteristic curve of the final model was 0.805 (95% confidence interval, 0.690-0.921). The cutoff value for the combined predictor was 0.57. Alternatively, when using C1/2t , which was strongly correlated with AUC, as the only independent risk factor, the analysis showed that the 3.47 μg/ml threshold provides favorable differentiation between the AKI and non-AKI groups. These results provide insightful information for therapeutic drug monitoring-guiding PMB dosing in clinical practice.
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Affiliation(s)
- Jing Wang
- Department of PharmacyNanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
| | - Yuanchen Li
- Department of PharmacyChina Pharmaceutical University Nanjing Drum Tower HospitalNanjingChina
| | - Siqi Huang
- Department of PharmacyNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineNanjingChina
| | - Min Wang
- Department of PharmacyNanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
- Nanjing Medical Center for Clinical PharmacyNanjingChina
| | - Lu Jin
- Department of PharmacyNanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
- Nanjing Medical Center for Clinical PharmacyNanjingChina
| | - Xuemei Luo
- Department of PharmacyNanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
- Nanjing Medical Center for Clinical PharmacyNanjingChina
| | - Xiaoliang Cheng
- Jiangsu Qlife Medical Technology Group Co., Ltd.NanjingChina
| | - Na Yang
- Department of PharmacyNanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
- Nanjing Medical Center for Clinical PharmacyNanjingChina
| | - Huaijun Zhu
- Department of PharmacyNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineNanjingChina
- Nanjing Medical Center for Clinical PharmacyNanjingChina
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Özkarakaş H, Özdemir Y, Tosun S, Tekgül ZT, Bilgin MU, Özmuk O, Çalık B. Risks of Polymyxin B Nephrotoxicity and Its Precursors in the Intensive Care Unit: A Retrospective Cohort Study. Cureus 2023; 15:e44301. [PMID: 37779820 PMCID: PMC10535720 DOI: 10.7759/cureus.44301] [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: 08/29/2023] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND AND AIM Polymyxin group antibiotics constitute a part of our limited arsenal in the treatment of multidrug-resistant gram-negative bacteria. However, their use is limited especially due to nephrotoxicity and other side effects. In this study, we primarily aimed to determine the effect of polymyxin B on the rate of nephrotoxicity in critically ill patients, and secondly to identify the factors that facilitate nephrotoxicity caused by polymyxin B. MATERIALS AND METHODS The study was designed as a retrospective cohort study and conducted by scanning patients aged 18 years or older who had been admitted to our intensive care unit (ICU) in 2022 and treated with polymyxin B for at least 72 hours. Patients without chronic renal failure and acute kidney injury (AKI) before starting polymyxin B therapy were included and AKI was examined after the use of polymyxin B. The patients were then divided into two groups, those with AKI and those without AKI. We tried to find factors that may facilitate AKI by comparing the two groups. RESULTS Of the patients, 26 were female and 34 were male. In 21 of the patients (35%), renal damage of varying degrees developed; these patients belonged to the nephrotoxicity (NT) group, while the rest belonged to the non-nephrotoxicity (non-NT) group. We found that advanced age (p=0.008), low baseline GFR (p=0.01), baseline creatinine (p=0.006), BMI (p=0.011), concomitant diseases (p<0.001), and days of use of polymyxin B (p=0.006) were statistically different between the two groups. In multivariate analysis of univariate analysis, we found that duration of polymyxin B use, BMI, and advanced age were independent risk factors for AKI development. CONCLUSION We found that 21 (35%) of 60 intensive care unit patients who had no previous history of kidney injury developed kidney injury after being treated with polymyxin B. We identified advanced age, high BMI, and duration of polymyxin B use as independent risk factors. Therefore, we recommend close monitoring of renal function and prompt intervention, particularly in patients with risk factors, during polymyxin B use.
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Affiliation(s)
- Hüseyin Özkarakaş
- Intensive Care Unit, University of Health Sciences Izmir Bozyaka Training and Research Hospital, Izmir, TUR
| | - Yeliz Özdemir
- Infectious Diseases and Clinical Microbiology, University of Health Sciences Izmir Bozyaka Training and Research Hospital, Izmir, TUR
| | - Selma Tosun
- Infectious Diseases and Clinical Microbiology, University of Health Sciences Izmir Bozyaka Training and Research Hospital, Izmir, TUR
| | - Zeki T Tekgül
- Anesthesiology and Reanimation, University of Health Sciences Izmir Bozyaka Training and Research Hospital, Izmir, TUR
| | - Mehmet U Bilgin
- Anesthesiology and Reanimation, Helios Klinikum Schleswig, Academic Teaching Hospital for the University of Kiel and Lubeck, Schleswig, DEU
| | - Ozkan Özmuk
- Critical Care Medicine, University of Health Sciences Izmir Bozyaka Training and Research Hospital, Izmir, TUR
| | - Bülent Çalık
- General Surgery, University of Health Sciences Izmir Bozyaka Training and Research Hospital, Izmir, TUR
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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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Xu Y, Liang P, Liu N, Dong D, Gu Q, Wang X. Correlation between the drug concentration of polymyxin B and polymyxin B-associated acute kidney injury in critically ill patients: A prospective study. Pharmacol Res Perspect 2022; 10:e01010. [PMID: 36206131 PMCID: PMC9542723 DOI: 10.1002/prp2.1010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/30/2022] [Indexed: 11/12/2022] Open
Abstract
In recent years, polymyxin B-associated acute kidney injury (PB-AKI) in critically ill patients has been reported frequently, but polymyxin B (PB) is mainly cleared through non-renal pathways, and the reasons of PB-AKI remain unclear. The aim of this study was to investigate the relationship between the serum concentration of PB and PB-AKI. We conducted a prospective cohort study in an intensive care unit between May 2019 and July 2021. Over the study period, 52 patients were included and divided into an AKI group (n = 26) and a non-AKI group (n = 26). The loading dose of PB in the AKI group was significantly higher than that in the non-AKI group. The C1/2 , Cmin , and estimated area under the concentration-time curve (AUC)0-24 of PB in the AKI group were dramatically increased compared with those in the non-AKI group, but the Cmax between the two groups showed no differences. Upon obtaining the ROC curve, the areas for the C1/2 , Cmin , and estimated AUC0-24 were 0.742, 0.710, and 0.710, respectively. The sensitivity was ascertained to be 61.54%, and the specificity was 76.92% when the cutoff value for the estimated AUC0-24 of 97.72 mg·h/L was used preferentially. The incidence of PB-AKI is high and related to the loading dose of PB. PB-AKI could be predicted when the estimated AUC0-24 of PB was greater than 97.72 mg·h/L.
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Affiliation(s)
- Ying Xu
- Surgical Intensive Care Unit (SICU), Department of General SurgeryJinling Hospital of Nanjing Medical UniversityNanjingChina,Intensive Care UnitDrum Tower Hospital Affiliated to Nanjing University School of MedicineNanjingJiangsuChina
| | - Pei Liang
- Department of PharmacyDrum Tower Hospital Affiliated to Nanjing University School of MedicineNanjingChina
| | - Ning Liu
- Intensive Care UnitDrum Tower Hospital Affiliated to Nanjing University School of MedicineNanjingJiangsuChina
| | - Danjiang Dong
- Intensive Care UnitDrum Tower Hospital Affiliated to Nanjing University School of MedicineNanjingJiangsuChina
| | - Qin Gu
- Intensive Care UnitDrum Tower Hospital Affiliated to Nanjing University School of MedicineNanjingJiangsuChina
| | - Xinying Wang
- Surgical Intensive Care Unit (SICU), Department of General SurgeryJinling Hospital of Nanjing Medical UniversityNanjingChina
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10
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Qu J, Qi TT, Qu Q, Long WM, Chen Y, Luo Y, Wang Y. Polymyxin B-Based Regimens for Patients Infected with Carbapenem-Resistant Gram-Negative Bacteria: Clinical and Microbiological Efficacy, Mortality, and Safety. Infect Drug Resist 2022; 15:1205-1218. [PMID: 35345474 PMCID: PMC8957303 DOI: 10.2147/idr.s357746] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/11/2022] [Indexed: 11/23/2022] Open
Abstract
Background The increasing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) represents a global healthcare crisis. This study explored the efficacy and safety of Polymyxin B (PMB)-based regimens and factors influencing their effectiveness. Methods Patients with CR-GNB infections treated with PMB for more than three days were enrolled in this retrospective study from 1st June 2018 to 30th April 2020. Data were collected on patient characteristics, bacterial culture, and drug-sensitivity test results; anti-infection treatment regimens, particularly details of PMB use; and adverse drug reactions. Clinical and microbiological efficacy, mortality, and safety of PMB-based regimens in CR-GNB infected patients were evaluated. Univariate analysis and multivariate logistic regression analyses were used to assess factors influencing efficacy and mortality. Results A total of 373 CR-GNB strains were cultured from 268 patients. About 41.04% of patients used PMB loading dose of 1.01 (0.84–1.69) mg/kg. Maintenance dose was 0.85 (0.82–1.00) mg/kg q12h. The clinical efficacy rate was 36.57% (98/268), the total bacterial clearance rate of PMB was 39.42%, and the all-cause mortality rate was 33.96%. The adverse drug reaction rate was 19.58%, among which the incidence of renal toxicity was highest (8.21%). Multivariate logistic regression analysis showed that clinical efficacy, bacterial clearance rate, and all-cause mortality were associated with patient-related facts, including mechanical ventilation use, underlying diseases (such as respiratory disease), the type and site of CR-GNB infection, and PMB administration timing and loading dose. Conclusion PMB is a relatively safe and effective antibiotic drug for treatment of critically ill patients with CR-GNB infection; however, PMB use should be subject to guidelines recommendations for early administration, loading administration, and adequate administration, which could help to improve the clinical efficacy, microbiological efficacy, and mortality.
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Affiliation(s)
- Jian Qu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China
| | - Ting-Ting Qi
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China
| | - Qiang Qu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China
| | - Wen-Ming Long
- Department of Pharmacy, Jingzhou District, Second People’s Hospital of Huaihua City, Huaihua, 418400, People’s Republic of China
| | - Ying Chen
- Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan, 430060, People’s Republic of China
| | - Yue Luo
- Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, 410300, People’s Republic of China
| | - Ying Wang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China
- Correspondence: Ying Wang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of China, Tel +86-15173198700, Fax +86-731-85292072, Email
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