During 2012, a total of 2968 isolates were consecutively collected from 59 medical centres in the USA and 15 European countries from hospitalised patients with
pneumonia.
Ceftolozane/tazobactam (
tazobactam at a fixed concentration of 4mg/L) and comparator agents were tested by reference methods, and MIC endpoints were interpreted by CLSI (2013) and EUCAST (2013) breakpoint criteria. Pseudomonas aeruginosa was the most common isolated pathogen (1019 strains; 34.3%), and
ceftolozane/tazobactam was the most active β-
lactam tested against P. aeruginosa (MIC50/90, 0.5/4 mg/L; 94.1% inhibited at ≤ 8 mg/L). P. aeruginosa exhibited moderate susceptibility to
meropenem (MIC50/90, 0.5/>8 mg/L; 73.7% susceptible),
ceftazidime (MIC50/90, 2/>32 mg/L; 73.6% susceptible),
cefepime (MIC50/90, 4/>16 mg/L; 76.5% susceptible),
piperacillin/tazobactam (MIC50/90, 8/>64 mg/L; 69.5% susceptible),
levofloxacin [MIC50/90, 0.5/>4 mg/L; 69.9/61.0% susceptible (CLSI/EUCAST criteria)] and
gentamicin (MIC50/90, 2/>8 mg/L; 80.7% susceptible).
Ceftolozane/tazobactam exhibited activity against many
ceftazidime-non-susceptible,
meropenem-non-susceptible and
piperacillin/tazobactam-non-susceptible, multidrug-resistant (MDR) and extensively
drug-resistant (XDR) P. aeruginosa isolates.
Ceftolozane/tazobactam was active (MIC50/90, 0.25/4mg/L; 94.6% inhibited at ≤ 8 mg/L) against 1530 Enterobacteriaceae, including activity against many MDR and XDR strains. MDR and XDR prevalence varied widely between countries both for P. aeruginosa (24.1% MDR and 17.1% XDR overall) and Enterobacteriaceae (15.4% MDR and 2.7% XDR overall). All β-
lactams had limited activity against Acinetobacter spp. and Stenotrophomonas maltophilia.
Ceftolozane/tazobactam demonstrated greater in vitro activity than currently available
cephalosporins,
carbapenems and
piperacillin/tazobactam when tested against P. aeruginosa. In addition,
ceftolozane/tazobactam demonstrated greater activity than contemporary
cephalosporins and
piperacillin/tazobactam when tested against most Enterobacteriaceae.