Dataset Information

Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children.

ABSTRACT: Infections due to carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes. Optimal treatment strategies for CRE infections continue to evolve. A lack of pediatric-specific comparative effectiveness data, uncertain pediatric dosing regimens for several agents, and a relative lack of new antibiotics with pediatric indications approved by the US Food and Drug Administration (FDA) collectively present unique challenges for children. In this review, we provide a framework for antibiotic treatment of CRE infections in children, highlighting relevant microbiologic considerations and summarizing available data related to the evaluation of FDA-approved antibiotics (as of September 2019) with CRE activity, including carbapenems, ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam, polymyxins, tigecycline, eravacycline, and plazomicin.

SUBMITTER: Chiotos K

PROVIDER: S-EPMC7047006 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children.

Chiotos Kathleen K Hayes Molly M Gerber Jeffrey S JS Tamma Pranita D PD

Journal of the Pediatric Infectious Diseases Society 20200201 1

Infections due to carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes. Optimal treatment strategies for CRE infections continue to evolve. A lack of pediatric-specific comparative effectiveness data, uncertain pediatric dosing regimens for several agents, and a relative lack of new antibiotics with pediatric indications approved by the US Food and Drug Administration (FDA) collectively present unique challenges for c ...[more]

PMID: 31872226

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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.

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.

Dataset Information

Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children.

Publications

Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children.

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