TY - JOUR
TI - In vitro activity of ceftolozane/tazobactam alone and in combination with amikacin against MDR/XDR Pseudomonas aeruginosa isolates from Greece
AU - Galani, I.
AU - Papoutsaki, V.
AU - Karantani, I.
AU - Karaiskos, I.
AU - Galani, L.
AU - Adamou, P.
AU - Deliolanis, I.
AU - Kodonaki, A.
AU - Papadogeorgaki, E.
AU - Markopoulou, M.
AU - Maraki, S.
AU - Damala, M.
AU - Prifti, E.
AU - Vagiakou, E.
AU - Petinaki, E.
AU - Fountoulis, K.
AU - Tsiplakou, S.
AU - Kirikou, H.
AU - Souli, M.
AU - Antoniadou, A.
AU - Giamarellou, H.
JO - The Journal of antimicrobial chemotherapy
PY - 2020
VL - 75
TODO - 8
SP - 2164-2172
PB - NLM (Medline)
SN - null
TODO - 10.1093/jac/dkaa160
TODO - 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
TODO - 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.
ER -