Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model
Por:
Montero, M, Ochoa, SD, Lopez-Causape, C, VanScoy, B, Luque, S, Sorli, L, Campillo, N, Angulo-Brunet, A, Padilla, E, Prim, N, Pomar, V, Rivera, A, Grau, S, Ambrose, PG, Oliver, A, Horcajada, JP
Publicada:
1 abr 2020
Resumen:
Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of UT and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and UT alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa 5T175 isolates with different susceptibility levels to UT. Static time-kill assays demonstrated superior synergistic or additive effect for UT plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. UT plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high riskclones resistant to C/T.
Filiaciones:
Montero, M:
Univ Auton Barcelona, CEXS Univ Pornpeu Fabra, Infect Pathol & Antimicrobials Res Grp IPAR, Infect Dis Serv,Inst Hosp Mar Invest Med IMIM,Hos, Barcelona, Spain
Ochoa, SD:
Univ Auton Barcelona, CEXS Univ Pornpeu Fabra, Infect Pathol & Antimicrobials Res Grp IPAR, Infect Dis Serv,Inst Hosp Mar Invest Med IMIM,Hos, Barcelona, Spain
Lopez-Causape, C:
IdISBa, Hosp Son Espases, Serv Microbiol & Unidad Invest, Palma De Mallorca, Spain
VanScoy, B:
Inst Clin Pharmacodynam, Schenectady, NY USA
Luque, S:
Hosp Mar, Pharm Serv, Barcelona, Spain
Sorli, L:
Univ Auton Barcelona, CEXS Univ Pornpeu Fabra, Infect Pathol & Antimicrobials Res Grp IPAR, Infect Dis Serv,Inst Hosp Mar Invest Med IMIM,Hos, Barcelona, Spain
Campillo, N:
Hosp Mar, Pharm Serv, Barcelona, Spain
Angulo-Brunet, A:
Univ Autonoma Barcelona, Dept Psicobiol & Metodol Ciencies Salut, Agencia Salut Publ Catalunya, Generalitat Catalunya, Barcelona, Spain
Padilla, E:
Lab Referencia Catalunya, Barcelona, Spain
Prim, N:
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 Clin Microbiol, Barcelona, Spain
Grau, S:
Hosp Mar, Pharm Serv, Barcelona, Spain
Ambrose, PG:
Inst Clin Pharmacodynam, Schenectady, NY USA
Oliver, A:
IdISBa, Hosp Son Espases, Serv Microbiol & Unidad Invest, Palma De Mallorca, Spain
Horcajada, JP:
Univ Auton Barcelona, CEXS Univ Pornpeu Fabra, Infect Pathol & Antimicrobials Res Grp IPAR, Infect Dis Serv,Inst Hosp Mar Invest Med IMIM,Hos, Barcelona, Spain
Bronze, Green Published
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