Colistin plus meropenem combination is synergistic in vitro against extensively drug-resistant Pseudomonas aeruginosa, including high-risk clones
Por:
Montero, MM, Ochoa, SD, Lopez-Causape, C, VanScoy, B, Luque, S, Sorli, L, Campillo, N, Padilla, E, Prim, N, Segura, C, Pomar, V, Rivera, A, Grau, S, Ambrose, PG, Oliver, A, Horcajada, JP
Publicada:
1 sep 2019
Resumen:
Background: Extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) and particularly P. aeruginosa high-risk clones, are of growing concern because treatment options are limited. For years, colistin monotherapy has been the only available treatment, but is well known that is not an optimal treatment. A combination of colistin with another antibiotic could be a possible therapeutic option.
Objectives: This study aimed to investigate effective antibiotic combinations against 20 XDR P. aeruginosa isolates obtained in a Spanish multicentre study (2015).
Methods: Forty-five checkerboards with six antipseudomonal antibiotics (amikacin, aztreonam, ceftazidime, meropenem, colistin, and ceftolozane/tazobactam) were performed to determine whether combinations were synergic or additive by fractional inhibitory concentration indices. On average, 15 different regimens were evaluated in duplicate against the three most prevalent high-risk clones (ST175, ST235, ST111) by time-kill analyses over 24 h. The combination showing synergism in the three high-risk clones was validated in all studied XDR isolates.
Results: In time-kill curves, the untreated control failed, as did each study regimen when administered alone. Two combinations were synergistic in the three high-risk clones that were initially studied: amikacin plus ceftazidime and colistin plus meropenem, with the second being the most effective combination. The efficacy of colistin plus meropenem was then tested in all 20 isolates. A synergistic bacterial density reduction for the duration of the study occurred in 80% of the entire XDR collection.
Conclusions: These data suggest that colistin plus meropenem may be a useful combination for the treatment of infections due to XDR P. aeruginosa, including high-risk clones, which warrants evaluation in a clinical trial. (C) 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.
Filiaciones:
Montero, MM:
Univ Autonoma Barcelona, CEXS Univ Pompeu Fabra Barcelona, Inst Hosp Mar Invest Med IMIM, Infect Dis Serv,Hosp Mar,Infect Pathol & Antimicr, Barcelona, Spain
Ochoa, SD:
Univ Autonoma Barcelona, CEXS Univ Pompeu Fabra Barcelona, Inst Hosp Mar Invest Med IMIM, Infect Dis Serv,Hosp Mar,Infect Pathol & Antimicr, Barcelona, Spain
Lopez-Causape, C:
Hosp Son Espases, IdISBa, Serv Microbiol, Palma De Mallorca, Spain
Hosp Son Espases, IdISBa, Unidad Invest, Palma De Mallorca, Spain
VanScoy, B:
Inst Clin Pharmacodynam, Schenectady, NY USA
Luque, S:
Hosp del Mar, Pharm Serv, Barcelona, Spain
Sorli, L:
Univ Autonoma Barcelona, CEXS Univ Pompeu Fabra Barcelona, Inst Hosp Mar Invest Med IMIM, Infect Dis Serv,Hosp Mar,Infect Pathol & Antimicr, Barcelona, Spain
Campillo, N:
Hosp del Mar, Pharm Serv, Barcelona, Spain
Padilla, E:
Lab Referencia Catalunya, Barcelona, Spain
Prim, N:
Lab Referencia Catalunya, Barcelona, Spain
Segura, C:
Lab Referencia Catalunya, Barcelona, Spain
Pomar, V:
Hosp Santa Creu & Sant Pau, Dept Internal Med, Infect Dis Unit, Barcelona, Spain
Rivera, A:
Hosp Santa Creu & Sant Pau, Dept Internal Med, Infect Dis Unit, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Clin Microbiol, Barcelona, Spain
Grau, S:
Hosp del Mar, Pharm Serv, Barcelona, Spain
Ambrose, PG:
Inst Clin Pharmacodynam, Schenectady, NY USA
Oliver, A:
Hosp Son Espases, IdISBa, Serv Microbiol, Palma De Mallorca, Spain
Hosp Son Espases, IdISBa, Unidad Invest, Palma De Mallorca, Spain
Horcajada, JP:
Univ Autonoma Barcelona, CEXS Univ Pompeu Fabra Barcelona, Inst Hosp Mar Invest Med IMIM, Infect Dis Serv,Hosp Mar,Infect Pathol & Antimicr, Barcelona, Spain
Green Accepted
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