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. 2020 Feb 26;6(4):FSO461.
doi: 10.2144/fsoa-2019-0074.

Synergistic activity of fosfomycin-meropenem and fosfomycin-colistin against carbapenem resistant Klebsiella pneumoniae: an in vitro evidence

Yamuna Devi Bakthavatchalam  1 , Abirami Shankar  1 , Dhiviya Prabaa Muthuirulandi Sethuvel  1 , Kalaiarasi Asokan  1 , Kalaiarasi Kanthan  1 , Balaji Veeraraghavan  1
Affiliations

Synergistic activity of fosfomycin-meropenem and fosfomycin-colistin against carbapenem resistant Klebsiella pneumoniae: an in vitro evidence

Yamuna Devi Bakthavatchalam et al. Future Sci OA. .

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 bla IMP. bla VIM. bla NDM. bla OXA-48 like, bla KPC. bla GES.#x00A0;and bla SPM. 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.

Keywords: Klebsiella pneumoniae; NDM; OXA-48-like; colistin; fosfomcyin; fosfomycin–colistin; fosfomycin–meropenem; meropenem; time-kill assay.

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Conflict of interest statement

Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Time-kill curves of fosfomycin–meropenem and fosfomycin–colistin combination.
(A) CR-Kp isolate showing synergy with fosfomcyin–meropenem combination; (B) isolate exhibits indifferent activity against fosfomcyin–meropenem; (C) and (D) isolate showing synergy and indifferent activity against fosfomycin–colistin combination. C: Colistin; col: Colistin; CR-Kp: Carbapenem-resistant Klebsiella pneumoniae; Fos: Fosfomycin; F: Fosfomycin; GC: Growth control; Mer: Meropenem.
Figure 2.
Figure 2.. Box plot showing median log10 CFU/ml of carbapenem resistant K. pneumoniae.
(A) Box plot showing median log10 CFU/ml of CR-Kp observed with fosfomycin, meropenem and fosfomycin–meropenem combination. (B) Box plot showing median log10 CFU/ml of CR-Kp observed with fosfomycin, colistin and fosfomycin–colistin combination. CFU: Colony-forming unit; CR-Kp: Carbapenem-resistant Klebsiella pneumoniae.
See this image and copyright information in PMC

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