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Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

ABSTRACT: BACKGROUND:Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing different carbapenem antibiotics for cUTI. Network meta-analysis is a useful tool to compare multiple treatments when there is limited or no direct evidence available. OBJECTIVE:The aim of this study is to compare the efficacy and safety of different carbapenems with alternative antibiotics for the treatment of cUTI. METHODS:Pubmed, Medline, CENTRAL, and Embase were searched in November 2018. Studies of cUTI patients receiving carbapenem were included. We performed network meta-analysis to estimate the risk ratio (RR) and 95% credible interval (CrI) from both direct and indirect evidence; traditional meta-analysis was also performed. Primary outcomes were clinical and microbiological treatment success. RESULTS:A total of 19 studies and 7380 patients were included in the analysis. Doripenem (DOPM) was associated with lower clinical treatment success rates than other carbapenems. Although the efficacy of other carbapenems by RRs with 95% CrIs did not show statistical differences, the cumulative rank probability indicated that meropenem/vaborbactam (MV), ertapenem (ETPM), and biapenem (BAPM) had higher clinical and microbiological treatment success rates; imipenem/cilastatin (IC) and MV showed higher risk of adverse events (AEs). CONCLUSIONS:MV was associated with higher treatment success rates for cUTI, especially for cUTI caused by carbapenem-resistant uropathogens, but also with higher risk of AEs. Our findings suggest MV as a first-choice treatment of carbapenem-resistant cUTI. ETPM, BAPM, and meropenem (MEPM) is another reasonable choice for cUTI empiric therapy.

SUBMITTER: Tan X

PROVIDER: S-EPMC6959894 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

Tan Xinmei X Pan Qiwen Q Mo Changgan C Li Xianshu X Liang Xueyan X Li Yan Y Lan Yingnian Y Chen Lingyuan L

Medicine 20200101 2

<h4>Background</h4>Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing different carbapenem antibiotics for cUTI. Network meta-analysis is a useful tool to compare multiple treatments when there i ...[more]

PMID: 31914101

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Project description:OBJECTIVES:This meta-analysis assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). METHODS:PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid MEDLINE, and Embase databases were accessed until November 21, 2019. In this meta-analysis, only randomized controlled trials comparing the treatment efficacy of novel β-lactam/β-lactamase inhibitor combinations with other antibiotics for cUTI/APN in adult patients were included. The outcomes included the clinical and microbiological responses, and risk of adverse events (AEs). RESULTS:Overall, the experimental group treated with a novel β-lactam/β-lactamase inhibitor combination and the control group comprised 1346 and 1376 patients, respectively. No significant difference in the clinical response rate at test-of-cure was observed between the novel β-lactam/β-lactamase inhibitor combination and comparators among the microbiological modified intent-to-treat population (89.1% vs 88.3%, OR, 1.04; 95% confidence interval [CI], 0.76-1.42; I = 28%) and the microbiologically evaluable population (95.2% vs 94.7%, OR, 1.12; 95% CI, 0.68-1.84; I = 0%). Additionally, the novel β-lactam/β-lactamase inhibitor combination was associated with a better microbiological response at test-of-cure than the comparators among the microbiological modified intent-to-treat population (74.4% vs 68.5%, OR, 1.34; 95% CI, 1.04-1.72; I = 45%) and microbiologically evaluable population (80.1% vs 72.5%, OR, 1.49; 95% CI, 1.06-2.10; I = 58%). Finally, the risk of AEs associated with the novel β-lactam/β-lactamase inhibitor combination was similar to that associated with the comparators (treatment-emergent adverse events [TEAE], OR, 1.04; 95% CI, 0.87-1.23; I = 19%; serious AEs, OR, 1.21; 95% CI, 0.82-1.76; I = 0%; treatment discontinuation for drug-related TEAE, OR, 077; 95% CI, 0.38-1.56, I = 5%). The all-cause mortality did not differ between the novel β-lactam/β-lactamase inhibitor combination and comparators (OR, 1.19; 95% CI, 0.37-3.81; I = 0%). CONCLUSIONS:The clinical and microbiological responses of novel β-lactam/β-lactamase inhibitor combinations in the treatment of cUTI/APN are similar to those of other available antibiotics. These combinations also share a safety profile similar to that of other antibiotics.

Project description:BACKGROUND:Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs. OBJECTIVE:To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs. METHODS:PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects. RESULTS:Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB. CONCLUSION:No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.

Project description:Hospital readmissions following severe infections are a major economic burden on the health care system and have a negative influence on patients' quality of life. Understanding the risk factors for readmission, particularly the extent to which they could be prevented, is of a great importance. In this study we evaluated potentially preventable risk factors for 60-day readmission in patients surviving hospitalization for complicated urinary tract infection (cUTI). This was a multinational, multicentre retrospective cohort study conducted in Europe and the Middle East. Our cohort included survivors of hospitalization due to cUTI during the years 2013-2014. The primary outcome was 60-day readmission following index hospitalization. Patient characteristics that could have influenced readmission: demographics, infection presentation and management, microbiological and clinical data; were collected via computerized medical records from infection onset up to 60 days after hospital discharge. Overall, 742 patients were included. The cohort median age was 68 years (interquartile range, (IQR) 55-80) and 43.3% (321/742) of patients were males. The all-cause 60-day readmission rate was 20.1% (149/742) and more than half were readmitted for infection [57.1%, (80/140)]. Recurrent cUTI was the most frequent cause for readmission [46.4% (65/140)]. Statistically significant risk factors associated with 60-day readmission in multivariable analysis were: older age (odds ratio (OR) 1.02 for an one-year increment, confidence interval (CI) 1.005-1.03), diabetes mellitus (OR 1.63, 95% CI 1.04-2.55), cancer (OR 1.7, 95% CI 1.05-2.77), previous urinary tract infection (UTI) in the last year (OR 1.8, 95% CI: 1.14-2.83), insertion of an indwelling bladder catheter (OR 1.62, 95% CI 1.07-2.45) and insertion of percutaneous nephrostomy (OR 3.68, 95% CI 1.67-8.13). In conclusion, patients surviving hospitalization for cUTI are frequently re-hospitalized, mostly for recurrent urinary infections associated with a medical condition that necessitated urinary interventions. Interventions to avoid re-admissions should target these patients.

Dataset Information

Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

Publications

Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

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