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Carbapenems versus alternative ?-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

ABSTRACT: BACKGROUND:Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. METHODS:To compare the effectiveness and safety of carbapenems versus ?-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and ?-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated. RESULTS:Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR?=?1.34, 95% CI?=?1.24-1.46) compared with ?-lactams. Meropenem (OR?=?1.36, 95% CI?=?1.18-1.56; OR?=?1.24, 95% CI?=?1.01-1.53), imipenem/cilastatin (OR?=?1.40, 95% CI?=?1.19-1.65; OR?=?1.31, 95% CI?=?1.04-1.67) showed higher effectiveness from that by ?-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus ?-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with ?-lactams. There was no significant difference between carbapenems and ?-lactams monotherapy or in combination. CONCLUSION:Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with ?-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.

SUBMITTER: Tang X

PROVIDER: S-EPMC7581108 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Carbapenems versus alternative β-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

Tang Xiuge X Chen Lingyuan L Li Yan Y Jiang Junsong J Li Xianshu X Liang Xueyan X

Medicine 20201001 43

<h4>Background</h4>Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment.<h4>Methods</h4>To compare the effectiveness and safety of carbapenems versus β-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and β-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated.<h4>Res ...[more]

PMID: 33120768

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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:BackgroundInvasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.MethodsWe conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study ?2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.ResultsNine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.ConclusionsCompared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.

Dataset Information

Carbapenems versus alternative ?-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

Publications

Carbapenems versus alternative β-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

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