In vitro activity of ceftolozane/tazobactam alone and in combination with amikacin against MDR/XDR Pseudomonas aeruginosa isolates from Greece. (25th May 2020)

• Record Type: Journal Article
• Authors: Galani, Irene; Papoutsaki, Vassiliki; Karantani, Irene; Karaiskos, Ilias; Galani, Lamprini; Adamou, Panagiota; Deliolanis, Ioannis; Kodonaki, Antigoni; Papadogeorgaki, Eleni; Markopoulou, Margarita; Maraki, Sofia; Damala, Maria; Prifti, Eleni; Vagiakou, Eleni; Petinaki, Efthimia; Fountoulis, Kimon; Tsiplakou, Sophia; Kirikou, Helen; Souli, Maria; Antoniadou, Anastasia; Giamarellou, Helen
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 8(2020)
• Page Start: 2164
• Page End: 2172
• Publication Date: 2020-05-25
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa160
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents against MDR non-MBL Pseudomonas aeruginosa isolates collected from nine Greek hospitals and we assessed the potential synergistic interaction between ceftolozane/tazobactam and amikacin. Methods: A total of 160 non-MBL P. aeruginosa isolates collected in 2016 were tested for susceptibility to ceftolozane/tazobactam and seven comparator agents including ceftazidime/avibactam. Time–kill assays were performed for synergy testing using ceftolozane/tazobactam 60 or 7.5 mg/L, corresponding to the peak and trough concentrations of a 1.5 g q8h dose, respectively, in combination with 69 mg/L amikacin, corresponding to the free peak plasma concentration. Synergy was defined as a ≥2 log10 cfu/mL reduction compared with the most active agent. Results: Overall, ceftolozane/tazobactam inhibited 64.4% of the P. aeruginosa strains at ≤4 mg/L. Colistin was the most active agent (MIC50/90, 0.5/2 mg/L; 96.3% susceptible) followed by ceftazidime/avibactam (MIC50/90, 4/16 mg/L; 80.6% susceptible). GES-type enzymes were predominantly responsible for ceftolozane/tazobactam resistance; 81.6% of the non-producers were susceptible. MICs for the P. aeruginosa isolates selected for synergy testing were 2–32 mg/L ceftolozane/tazobactam and 2–128 mg/L amikacin. The combination of ceftolozane/tazobactam with amikacin was synergistic against 85.0% of all the isolates tested and against 75.0% of the GES producers. No antagonistic interactions were observed. Conclusions: Ceftolozane/tazobactam demonstrated good in vitro activity against MDR/XDR P. aeruginosa clinical isolates, including strains with co-resistance to other antipseudomonal drugs. In combination with amikacin, a synergistic interaction at 24 h was observed against 85.0% of P. aeruginosa strains tested, including isolates with ceftolozane/tazobactam MICs of 32 mg/L or GES producers.