Joan Gómez-Junyent1, Eva Benavent1, Yanik Sierra2, Cristina El Haj1, Laura Soldevila1, Benjamín Torrejón3, Raul Rigo-Bonnin4, Fe Tubau2, Javier Ariza5, Oscar Murillo6. 1. Infectious Diseases Service, Laboratory of Experimental Infection, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain. 2. Department of Microbiology, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain. 3. Centres Científics i Tecnològics, Universitat de Barcelona, Barcelona, Spain. 4. Department of Clinical Laboratory, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain. 5. Infectious Diseases Service, Laboratory of Experimental Infection, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain; Spanish Network for the Research in Infectious Diseases (REIPIRD12/0015), Instituto de Salud Carlos III, Madrid, Spain. 6. Infectious Diseases Service, Laboratory of Experimental Infection, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain; Spanish Network for the Research in Infectious Diseases (REIPIRD12/0015), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: omurillo@bellvitgehospital.cat.
Abstract
OBJECTIVES: Ceftolozane/tazobactam is a potential tool for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa), but its efficacy against some difficult-to-treat infections has not been well defined. METHODS: Using an in vitro pharmacodynamic biofilm model, this study evaluated the comparative efficacy of ceftolozane/tazobactam against MDR/extensively drug-resistant (XDR) P. aeruginosa strains, alone and in combination with colistin. Simulated regimens of ceftolozane/tazobactam (2 g/1 g every 8 h), meropenem (2 g every 8 h) and ceftazidime (2 g every 8 h), alone and in combination with colistin (continuous infusion) were evaluated against three colistin-susceptible and ceftazidime-resistant strains: MDR-HUB1, ceftolozane/tazobactam-susceptible and meropenem-susceptible; XDR-HUB2, ceftolozane/tazobactam-susceptible and meropenem-resistant; MDR-HUB3, ceftolozane/tazobactam-resistant and meropenem-susceptible. Antibiotic efficacy was evaluated by decreases in bacterial counts (Δlog CFU/mL) from biofilm-embedded bacteria over 54 h. Resistance emergence was screened. RESULTS: Among monotherapies, ceftolozane/tazobactam had low killing but no resistance appeared, ceftazidime was ineffective, colistin was initially effective but regrowth and resistance occurred, and meropenem was bactericidal against carbapenem-susceptible strains. Ceftolozane/tazobactam plus colistin was the most effective combination against the meropenem-resistant XDR-HUB2 strain (Δlog CFU/mL 54-0 h = -4.42 vs. -3.54 for meropenem-colistin; P = 0.002), whereas this combination against MDR-HUB1 (-4.36) was less effective than meropenem-colistin (-6.25; P < 0.001). Ceftolozane/tazobactam plus colistin was ineffective against the ceftolozane/tazobactam-resistant strain; meropenem plus colistin was the most bactericidal therapy (-6.37; P < 0.001 vs. others). Combinations of active beta-lactams plus colistin prevented the emergence of colistin-resistant strains. CONCLUSIONS: Combinations of colistin plus ceftolozane/tazobactam and meropenem were the most appropriate treatments for biofilm-related infections caused by XDR and MDR P. aeruginosa strains, respectively. These combinations could be considered as potential treatment options for these difficult to treat infections.
OBJECTIVES:Ceftolozane/tazobactam is a potential tool for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa), but its efficacy against some difficult-to-treat infections has not been well defined. METHODS: Using an in vitro pharmacodynamic biofilm model, this study evaluated the comparative efficacy of ceftolozane/tazobactam against MDR/extensively drug-resistant (XDR) P. aeruginosa strains, alone and in combination with colistin. Simulated regimens of ceftolozane/tazobactam (2 g/1 g every 8 h), meropenem (2 g every 8 h) and ceftazidime (2 g every 8 h), alone and in combination with colistin (continuous infusion) were evaluated against three colistin-susceptible and ceftazidime-resistant strains: MDR-HUB1, ceftolozane/tazobactam-susceptible and meropenem-susceptible; XDR-HUB2, ceftolozane/tazobactam-susceptible and meropenem-resistant; MDR-HUB3, ceftolozane/tazobactam-resistant and meropenem-susceptible. Antibiotic efficacy was evaluated by decreases in bacterial counts (Δlog CFU/mL) from biofilm-embedded bacteria over 54 h. Resistance emergence was screened. RESULTS: Among monotherapies, ceftolozane/tazobactam had low killing but no resistance appeared, ceftazidime was ineffective, colistin was initially effective but regrowth and resistance occurred, and meropenem was bactericidal against carbapenem-susceptible strains. Ceftolozane/tazobactam plus colistin was the most effective combination against the meropenem-resistant XDR-HUB2 strain (Δlog CFU/mL 54-0 h = -4.42 vs. -3.54 for meropenem-colistin; P = 0.002), whereas this combination against MDR-HUB1 (-4.36) was less effective than meropenem-colistin (-6.25; P < 0.001). Ceftolozane/tazobactam plus colistin was ineffective against the ceftolozane/tazobactam-resistant strain; meropenem plus colistin was the most bactericidal therapy (-6.37; P < 0.001 vs. others). Combinations of active beta-lactams plus colistin prevented the emergence of colistin-resistant strains. CONCLUSIONS: Combinations of colistin plus ceftolozane/tazobactam and meropenem were the most appropriate treatments for biofilm-related infections caused by XDR and MDR P. aeruginosa strains, respectively. These combinations could be considered as potential treatment options for these difficult to treat infections.
Authors: Alba Ribera; Eva Benavent; Cristina El-Haj; Joan Gomez-Junyent; Fe Tubau; Raul Rigo-Bonnin; Javier Ariza; Oscar Murillo Journal: Antimicrob Agents Chemother Date: 2019-10-22 Impact factor: 5.191
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