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.

Keywords: Klebsiella pneumoniae carbapenemase; gram-negative resistance; multidrug-resistant organism; pediatrics.

Figure 1.

Suggested framework for antibiotic selection for children with carbapenemase–carbapenem-resistant Enterobacteriaceae (CP-CRE) and non–CP-CRE. ^aMeropenem administered over 3 hours can achieve target serum concentrations for isolates up to 8 μg/mL in healthy children. ^bFluoroquinolones are variably active against CRE. If susceptible, these agents can be used as part of combination regimens or as monotherapy for mild to moderate infections. ^cAminoglycosides are recommended as first-line agents for use in combination for systemic infections given pediatric clinical experience and familiarity with dosing. Aminoglycosides may also be used for cystitis as monotherapy. ^dThe polymyxin class includes colistin and polymyxin B. Polymyxin B is preferred given ease of dosing and more reliable pharmacokinetics for nonurinary sources of infection. For urinary tract infections, colistin is preferred. ^eConsider in children with epidemiologic link to a MBL-endemic region (eg, South Asia) or known history of MBL-producing isolate. ^fIf the MIC for ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-relebactam is at the breakpoint, addition of a second agent could be considered, with aminoglycosides preferred. Abbreviations: Alt, alternative; βL-βLI, β-lactam/β-lactamase inhibitor; MBL, metallo-β-lactamase; MIC, minimum inhibitory concentration. (cUTIs) and (cIAIs;