A systematic scoping review of faropenem and other oral penems: treatment of Enterobacterales infections, development of resistance and cross-resistance to carbapenems

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Abstract
Background: Antimicrobial resistance is an urgent global healthcare concern. Beyond carbapenems as broad-spectrum, often ‘last resort’ antibiotics, oral penem antibiotics currently are approved only in Japan and India, used for the treatment of indications including urinary tract infections (UTIs). Exploring oral penem use to better understand the impact of antibiotic resistance on public health would help inform the management of infectious diseases, including UTIs. Scoping Review Methodology: This scoping review investigated the impact of faropenem and other oral penems on Enterobacterales infection treatment and evaluated evidence for faropenem resistance and cross-resistance to carbapenems. PubMed, Embase, J-STAGE and CiNii were searched for relevant English- or Japanese-language articles published between 1 January 1996 and 6 August 2021. Key Findings: From 705 unique publications, 29 eligible articles were included (16 in vitro studies; 10 clinical trials; 2 in vitro and in vivo studies; and 1 retrospective medical chart review). Limited evidence described faropenem to treat infectious disease; only four randomized clinical trials were identified. Faropenem dosing regimens varied broadly within and between indications. One study indicated potential dependence of penem efficacy on underlying antibiotic resistance mechanisms, while several studies reported UTI persistence or recurrence after faropenem treatment. In vitro MIC data suggested some potential bacterial resistance to faropenem, while limited clinical data showed resistance emergence after faropenem treatment. Preliminary in vitro evidence suggested faropenem resistance might foster cross-resistance to carbapenems. Overall, very limited clinical evidence describes faropenem for treating infectious diseases. Preclinical and clinical research investment and dedicated community surveillance monitoring is crucial for understanding faropenem treatment patterns, resistance and potential cross-resistance to carbapenems.

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