María M Montero1, Sandra Domene Ochoa2, Carla López-Causapé3, Brian VanScoy4, Sonia Luque5, Luisa Sorlí2, Núria Campillo5, Eduardo Padilla6, Núria Prim6, Concepción Segura6, Virginia Pomar7, Alba Rivera8, Santiago Grau5, Paul G Ambrose4, Antonio Oliver3, Juan P Horcajada9. 1. Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra Barcelona, Spain. Electronic address: 95422@parcdesalutmar.cat. 2. Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra Barcelona, Spain. 3. Servicio de Microbiología y Unidad de Investigación, Hospital Son Espases, IdISBa, Palma de Mallorca, Spain. 4. Institute for Clinical Pharmacodynamics, Schenectady, NY, USA. 5. Pharmacy Service, Hospital del Mar, Barcelona, Spain. 6. Laboratori de Referència de Catalunya, Barcelona, Spain. 7. Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 8. Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Clinical Microbiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 9. Infectious Diseases Service, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra Barcelona, Spain. Electronic address: jhorcajada@psmar.cat.
Abstract
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 24h. 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.
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 24h. 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.
Authors: María Montero; Sandra Domene Ochoa; Carla López-Causapé; Brian VanScoy; Sonia Luque; Luisa Sorlí; Núria Campillo; Ariadna Angulo-Brunet; Eduardo Padilla; Núria Prim; Virginia Pomar; Alba Rivera; Santiago Grau; Paul G Ambrose; Antonio Oliver; Juan P Horcajada Journal: Antimicrob Agents Chemother Date: 2020-03-24 Impact factor: 5.191
Authors: Rachel Wheatley; Julio Diaz Caballero; Natalia Kapel; Fien H R de Winter; Pramod Jangir; Angus Quinn; Ester Del Barrio-Tofiño; Carla López-Causapé; Jessica Hedge; Gabriel Torrens; Thomas Van der Schalk; Basil Britto Xavier; Felipe Fernández-Cuenca; Angel Arenzana; Claudia Recanatini; Leen Timbermont; Frangiscos Sifakis; Alexey Ruzin; Omar Ali; Christine Lammens; Herman Goossens; Jan Kluytmans; Samir Kumar-Singh; Antonio Oliver; Surbhi Malhotra-Kumar; Craig MacLean Journal: Nat Commun Date: 2021-04-28 Impact factor: 14.919