Dataset Information

The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis.

ABSTRACT: Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting.We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016.Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035-1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038-2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089-2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004-1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009).Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

SUBMITTER: Andreatos N

PROVIDER: S-EPMC5534219 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis.

Andreatos Nikolaos N Flokas Myrto Eleni ME Apostolopoulou Anna A Alevizakos Michail M Mylonakis Eleftherios E

Open forum infectious diseases 20170524 3

<h4>Background</h4>Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting.<h4>Methods</h4>We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016.<h4>Results</h4>Thirty-two trials, reporting on 5724 patients ...[more]

PMID: 28761897

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Project description:BackgroundAntipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN.MethodsPubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763.ResultsEighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate.ConclusionsMeropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.

Project description:BackgroundCefepime is a fourth-generation cephalosporin antibiotic used to treat a variety of infections. The US Food and Drug Administration approved its use in certain types of infections among pediatric patients, and yet there have been mixed data about its efficacy and safety in this population.ObjectiveThe objective of this review is to compare efficacy and all-cause mortality of cefepime to other clinically indicated antibiotics among children.MethodsWe conducted a systematic search of MEDLINE, EMBASE, CENTRAL, LILACS, and clinicaltrials.gov databases through February 8, 2016. We included randomized controlled trials comparing cefepime to other clinical antibiotics, placebo, or no treatment in children aged 0-19 years in the inpatient setting with clinical signs of infection. The primary outcome of interest was all-cause mortality. The secondary outcomes were success rate, treatment failure, and incidence of adverse events. Study quality was assessed using the Cochrane Risk of Bias Assessment Tool.ResultsSeventeen studies met the inclusion criteria. There was a total of 1,285 participants included, 624 participants in the cefepime arm and 661 in the comparison arm. A random effects meta-analysis for all-cause mortality showed no difference in rates of mortality between cefepime and comparator antibiotics with a mortality risk ratio of 0.88 (95% CI: 0.71-1.08). For the secondary outcomes of success rate and treatment failure, a random effects model meta-analysis conducted of the studies showed no difference in rate between cefepime and comparator antibiotics with an overall risk ratio of 0.98 (95% CI: 0.92-1.05) and 1.04 (95% CI: 0.91-1.19), respectively. Adverse events were not statistically assessed given widespread heterogeneity. Overall, the studies had unclear risk of bias and were limited by high heterogeneity and methodological flaws.ConclusionThe efficacy and safety of cefepime in pediatric patients remain unclear despite the inclusion of newer trials since the last index systematic review conducted a decade ago.

Dataset Information

The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis.

Publications

The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis.

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