Synergistic Activity of fosfomycin–meropenem and fosfomycin–colistin Against Carbapenem Resistant Klebsiella Pneumoniae : an In Vitro Evidence

Abstract

Aim: To evaluate the antibacterial activity of fosfomycin–meropenem and fosfomycin–colistin combinations against carbapenem-resistant Klebsiella pneumoniae (CR-Kp). Methods: A total of 50 CR-Kp isolates recovered from blood cultures were included in this study. All the CR-Kp isolates were screened for the presence of carbapenem resistant genes blaIMP. blaVIM. blaNDM. blaOXA-48 like, blaKPC. blaGES.#x00A0;and blaSPM. Combination testing of fosfomycin–meropenem and fosfomycin–colistin were performed using time-kill assay. Results: Fosfomycin–meropenem combination showed synergy in 20% of the tested CR-Kp isolates. While, fosfomycin–colistin exhibited synergy against 16% of the isolates. A total of 68% (n = 34) of CR-Kp isolates were characterised as OXA-48-like producers and 22% (n = 11) as NDM producers. Synergistic activity of these combinations was observed against OXA-48, NDM and NDM + OXA-48 co-producers. Conclusion: Considerable synergistic antibacterial activity of fosfomycin–meropenem and fosfomycin–colistin was not observed against CR-Kp isolates. Therefore, these combinations may not be promising for infections associated with CR-Kp.

In vitroassessment of the antibacterial effects of the combinations of fosfomycin, colistin, trimethoprim and nitrofurantoin against multi‐drug–resistantEscherichia coli

“…The same effects of FOS/COL (Yu et al 2018;Ku et al 2019;Bakthavatchalam et al 2020) and COL/NIT (Pogue et al 2011;Corvec et al 2013;Ceccarelli et al 2015) were also reported against other Gram-negative bacteria. This suggests a wide-spectrum of activity of COL combinations with FOS and NIT against different Gram-negative pathogens.…”

Fosfomycin Dosing Regimens based on Monte Carlo Simulation for Treated Carbapenem-ResistantEnterobacteriaceaeInfection

“…Three of the patients who achieved bacterial eradication were being treated for VAP with septic shock and received fosfomycin in combination with colistin. Thus, our results are similar to prior studies which suggest the efficacy of fosfomycin in combination with other antimicrobial agents, particularly colistin, can be improved [ 5 8 20 26 – 28 ]. In fact, synergy found with fosfomycin combination therapy may result in reducing the fosfomycin MIC against CRE isolates [ 10 28 ].…”

“…Thus, our results are similar to prior studies which suggest the efficacy of fosfomycin in combination with other antimicrobial agents, particularly colistin, can be improved [5,8,20,[26][27][28]. In fact, synergy found with fosfomycin combination therapy may result in reducing the fosfomycin MIC against CRE isolates [10,28].…”

Assessment of In-Vitro Synergy of Fosfomycin with Meropenem, Amikacin and Tigecycline in Whole Genome Sequenced Extended and Pan Drug Resistant Klebsiella Pneumoniae: Exploring A Colistin Sparing Protocol

“…TKA not only confirmed but demonstrated even higher synergy against the representative XDR NDM K. pneumoniae isolate. Bactericidal activity was observed as early as 6 h of incubation with 0.25 MIC fosfomycin (16 mg/L) and 1/32 MEM MIC (2 mg/L) which persisted for 24 h. Synergy levels achieved in OXA-232/48 producing Klebsiella pneumoniae in our study was 94% while other studies reported 20–42% synergy [ 21 , 22 ]. Samonis et al reported over 70% synergy in KPC producing Klebsiella pneumoniae [ 23 ].…”