Fosfomycin-meropenem synergistic combination against NDM carbapenemase-producing Klebsiella pneumoniae strains

Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing threat to global public health. Treatment of CPE isolates, like New Delhi metallo-β-lactamase (NDM), is limited and often necessitates combination therapies. The aim of this study was to evaluate the synergistic meropenem/ fosfomycin...

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Published inThe New microbiologica Vol. 46; no. 3; pp. 264 - 270
Main Authors Della Rocca, Maria Teresa, Di Caprio, Giovanni, Colucci, Francesca, Merola, Filomena, Panetta, Vittorio, Cordua, Emanuele, Greco, Rita
Format Journal Article
LanguageEnglish
Published Pavia Edizioni Medico Scientifiche 01.07.2023
Subjects
Carbapenemase
Ceftazidime
Colistin
Fosfomycin
Klebsiella
Meropenem
Metallo-β-lactamase
Metallography
Multidrug resistance
Pneumonia
Public health
Tazobactam
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Summary:Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing threat to global public health. Treatment of CPE isolates, like New Delhi metallo-β-lactamase (NDM), is limited and often necessitates combination therapies. The aim of this study was to evaluate the synergistic meropenem/ fosfomycin combination against K.pneumoniae-producing NDM isolates. Fosfomycin/meropenem, fosfomycin/colistin and meropenem/colistin were tested alone and in combination, using e-test and time-kill assay against 20 clinical carbapenemase-producing K. pneumonia (CPKp NDM) isolates collected from September 2022 to December 2022. K. pneumoniae strains were resistant to meropenem, ceftazidime/avibactam and ceftolozano/tazobactam, 75% and 80% of isolates were susceptible for cefiderocol and for colistin respectively. Fosfomycin/meropenem combination was synergic in 95% (n=19) strains. Fosfomycin/colistin and colistin/meropenem combination showed only 10% synergistic combination strains. In 16 isolates (80%) indifference action for fosfomycin/colistin and colistin/meropenem was reported. For 0.8% of CpKP NDM isolates colistin/meropenem and fosfomycin/colistin combinations found to be antagonistic. In this study, time kill assay showed combination therapies action versus K.pneumoniae metallo-b-lactamase producing (NDM) strains and confirmed the synergistic action of fosfomycin/meropenem combination. In vitro synergy testing should be routinely performed in multidrug resistance infections and combo therapies can be used as a possible alternative in targeted patients with the goal of reducing overall antibiotic costs.
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ISSN:1121-7138