Dataset Information

Triple Versus Double Therapy for the Treatment of Severe Infections Caused by Carbapenem-Resistant Enterobacteriaceae: A Systematic Review and Meta-Analysis.

ABSTRACT: Introduction:The role of combination treatment in the management of carbapenem-resistant Enterobacteriaceae infections (CRE) is still unclear. There have been no meta-analysis comparing the efficiency of triple therapy in treating CRE infections with that of double therapy. In this perspective, we conducted a meta-analysis to clarify whether triple therapy is superior to double therapy in treating patients with CRE infections. Methods:We performed a systematic review, using PubMed and Embase without any restrictions until October 2019. Risk ratio (RR) with 95% CI were pooled to evaluate the effect of intervention. Results:A total of 33 studies with 1,441 subjects were identified. Pooled analysis showed that triple therapy was not associated with a reduced mortality compared with double therapy (HR 0.99 95% CI 0.85-1.14, P = 0.85). Conclusions:This meta-analysis suggests that triple therapy is not superior to double therapy in the treatment of patients with CRE infections, although the quality of evidence is generally low based on current literatures. Future well-defined, randomized controlled trials will be required to elucidate the role of triple therapy in the treatment of CRE infections.

SUBMITTER: Wang L

PROVIDER: S-EPMC7005522 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Triple Versus Double Therapy for the Treatment of Severe Infections Caused by Carbapenem-Resistant Enterobacteriaceae: A Systematic Review and Meta-Analysis.

Wang Lei L Tong Xiang X Huang Jizhen J Zhang Li L Wang Dongguang D Wu Man M Liu Tao T Fan Hong H

Frontiers in pharmacology 20200130

<h4>Introduction</h4>The role of combination treatment in the management of carbapenem-resistant Enterobacteriaceae infections (CRE) is still unclear. There have been no meta-analysis comparing the efficiency of triple therapy in treating CRE infections with that of double therapy. In this perspective, we conducted a meta-analysis to clarify whether triple therapy is superior to double therapy in treating patients with CRE infections.<h4>Methods</h4>We performed a systematic review, using PubMed ...[more]

PMID: 32082166

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Project description:Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new ?-lactam/?-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE.

Project description:Background:The efficacy of ceftazidime-avibactam-a cephalosporin-?-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown. Methods:Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results:Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin. Conclusions:Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.

Dataset Information

Triple Versus Double Therapy for the Treatment of Severe Infections Caused by Carbapenem-Resistant Enterobacteriaceae: A Systematic Review and Meta-Analysis.

Publications

Triple Versus Double Therapy for the Treatment of Severe Infections Caused by Carbapenem-Resistant Enterobacteriaceae: A Systematic Review and Meta-Analysis.

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