Compassionate use of meropenem/vaborbactam for infections caused by KPC-producing Klebsiella pneumoniae: a multicentre study.

Abstract

Objectives:

To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam.

Methods:

A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included.

Results:

The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy >48 h after infection onset. Outcomes were unrelated to the isolate's ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia.

Conclusions:

With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.

• Authors: Mario Tumbarello, Francesca Raffaelli, Antonio Cascio, Marco Falcone, Liana Signorini, Cristina Mussini, Francesco Giuseppe De Rosa, Angela Raffaella Losito, Gennaro De Pascale, Renato Pascale, Daniele Roberto Giacobbe, Alessandra Oliva, Alberto Farese, Paola Morelli, Giusy Tiseo, Marianna Meschiari, Paola Del Giacomo, Francesca Montagnani, Massimiliano Fabbiani, Joel Vargas, Teresa Spanu, Matteo Bassetti, Mario Venditti, Pierluigi Viale
• Journal: JAC-antimicrobial resistance (JAC Antimicrob Resist) Vol. 4 Issue 1 Pg. dlac022 (Mar 2022) ISSN: 2632-1823 [Electronic] England
• PMID: 35265842 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.