@article{3020787,
    title = "In vitro activity of ceftolozane/tazobactam alone and in combination with amikacin against MDR/XDR Pseudomonas aeruginosa isolates from Greece",
    author = "Galani, I. and Papoutsaki, V. and Karantani, I. and Karaiskos, I. and Galani, L. and Adamou, P. and Deliolanis, I. and Kodonaki, A. and Papadogeorgaki, E. and Markopoulou, M. and Maraki, S. and Damala, M. and Prifti, E. and Vagiakou, E. and Petinaki, E. and Fountoulis, K. and Tsiplakou, S. and Kirikou, H. and Souli, M. and Antoniadou, A. and Giamarellou, H.",
    journal = "The Journal of antimicrobial chemotherapy",
    year = "2020",
    volume = "75",
    number = "8",
    pages = "2164-2172",
    publisher = "NLM (Medline)",
    doi = "10.1093/jac/dkaa160",
    keywords = "amikacin;  antiinfective agent;  ceftolozane;  cephalosporin derivative;  tazobactam, Greece;  human;  microbial sensitivity test;  multidrug resistance;  Pseudomonas aeruginosa;  Pseudomonas infection, Amikacin;  Anti-Bacterial Agents;  Cephalosporins;  Drug Resistance, Multiple, Bacterial;  Greece;  Humans;  Microbial Sensitivity Tests;  Pseudomonas aeruginosa;  Pseudomonas Infections;  Tazobactam",
    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. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com."
}