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- Title
In vitro activity and post-antibiotic effects of colistin in combination with other antimicrobials against colistin-resistant KPC-producing Klebsiella pneumoniae bloodstream isolates.
- Authors
Gaibani, Paolo; Lombardo, Donatella; Lewis, Russell E.; Mercuri, Marcella; Bonora, Sonia; Landini, Maria Paola; Ambretti, Simone
- Abstract
Objectives Combination therapy is recommended for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal regimen for colistin-resistant strains is unknown. We compared the synergistic activity and post-antibiotic effect (PAE) of colistin in combination with other antimicrobials against colistin-susceptible and -resistant KPC-Kp bloodstream isolates. Methods The genotypes of nine colistin-susceptible and eight colistin-resistant KPC-Kp bloodstream isolates were analysed using PCR and amplicon sequencing. Combinations of colistin, meropenem, tigecycline, rifampicin and teicoplanin were then screened using the Etest, a chequerboard assay and time–kill studies. Synergistic combinations were also analysed with respect to the PAE in time–kill curves and the PAE at clinically achievable concentrations. Results Insertional inactivation of the PhoQ/PhoB two-component regulatory system by mgrB-IS5 was identified in 6/8 (75%) colistin-resistant KPC-Kp. Colistin/rifampicin combinations resulted in no interactions [fractional inhibitory concentration (FIC) indices 1.5–2] for colistin-susceptible strains, but were uniformly synergistic (FIC indices 0.1–0.4) against colistin-resistant KPC-Kp. Time–kill kinetic analysis, at clinically achievable fixed concentrations of rifampicin and colistin, confirmed synergy and produced persistent growth inhibition (3 h) of colistin-resistant KPC-Kp strains exposed to colistin/rifampicin or colistin/rifampicin/tigecycline combinations. Conclusions Combinations of colistin plus rifampicin, and less frequently tigecycline, exhibited synergistic activity in vitro against colistin-resistant KPC-Kp strains.
- Subjects
KLEBSIELLA infections; KLEBSIELLA pneumoniae; ANTIBIOTICS; COLISTIN; RIFAMPIN; DRUG resistance in bacteria; THERAPEUTICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2014, Vol 69, Issue 7, p1856
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dku065