Details

Autor(en) / Beteiligte

• Gaibani, Paolo
• Lombardo, Donatella
• Lewis, Russell E
• Mercuri, Marcella
• Bonora, Sonia
• Landini, Maria Paola
• Ambretti, Simone

Titel

In vitro activity and post-antibiotic effects of colistin in combination with other antimicrobials against colistin-resistant KPC-producing Klebsiella pneumoniae bloodstream isolates

Ist Teil von

• Journal of antimicrobial chemotherapy, 2014-07, Vol.69 (7), p.1856-1865

Ort / Verlag

England: Oxford Publishing Limited (England)

Erscheinungsjahr

2014

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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. 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. 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. Combinations of colistin plus rifampicin, and less frequently tigecycline, exhibited synergistic activity in vitro against colistin-resistant KPC-Kp strains.