Ceftolozane/tazobactam activity tested against aerobic Gram-negative organisms isolated from intra-abdominal and urinary tract infections in European and United States hospitals (2012).
Ceftolozane/tazobactam is under clinical development for treatment of complicated intra-abdominal infections (IAI), complicated urinary tract infections (UTI) and ventilator-associated pneumonia. We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Gram-negative aerobic bacteria causing IAI and healthcare-associated UTI (HCA-UTI). The organisms were consecutively collected from January to December 2012 from 59 medical centers located in the United States (USA) and 15 European countries by the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS). The collection included 809 organisms from IAI and 2474 organisms from HCA-UTI, and susceptibility testing was performed by reference broth microdilution methods as described by the Clinical and Laboratory Standards Institute (CLSI) M07-A9 document. Overall, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most frequently isolated pathogens from both infection types. Ceftolozane/tazobactam was very active against E. coli (MIC50/90, 0.25/0.5 mg/L; 98.5-99.9% inhibited at an MIC of ≤8 mg/L) and retained activity against many of the multidrug-resistant (MDR; MIC50/90, 0.5/2->32 mg/L) and ESBL-phenotype strains (MIC50/90, 0.5/2-32 mg/L). Ceftolozane/tazobactam was active against most K. pneumoniae strains (MIC50/90, 0.25/16 mg/L, 88.9-89.6% inhibited at an MIC of ≤8 mg/L), but some ESBL-phenotype (MIC50/90, 4-8/>32 mg/L) and MDR (MIC50/90, 16/>32 mg/L) isolates exhibited elevated MIC values. Ceftolozane/tazobactam was the most active agent tested against P. aeruginosa (MIC50/90, 0.5/4 mg/L; 93.4-95.7% inhibited at ≤8 mg/L) and retained potency against many MDR (MIC50/90, 2-4/>32 mg/L), ceftazidime-nonsusceptible (MIC50/90, 2-4/>32 mg/L) and meropenem-nonsusceptible (MIC50/90, 2/>32 mg/L) strains. Ceftolozane/tazobactam was also active against Klebsiella oxytoca (MIC50/90, ≤0.12-0.25/0.5-1 mg/L), Enterobacter spp. (MIC50/90, 0.25-0.5/4-8 mg/L), Citrobacter spp. (MIC50/90, 0.25/2-32 mg/L), Proteus mirabilis (MIC50/90, 0.5/0.5 mg/L), indole-positive Proteae (MIC50/90, 0.25/0.5-1 mg/L), and Serratia spp. (MIC50/90, 0.5/1-2 mg/L). In summary, ceftolozane/tazobactam demonstrated potent in vitro activity when tested against contemporary aerobic Gram-negative pathogens causing IAI and HCA-UTI in USA and European medical centers.
JMI Laboratories, North Liberty, IA, USA. Electronic address: helio-sader@jmilabs.com.
Helio S
HS
Sader
JMI Laboratories, North Liberty, IA, USA.
David J
DJ
Farrell
JMI Laboratories, North Liberty, IA, USA.
Robert K
RK
Flamm
JMI Laboratories, North Liberty, IA, USA.
Ronald N
RN
Jones
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D002954:Citrobacter / Q000187:drug effects; D003428:Cross Infection / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D005060:Europe; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D059413:Intraabdominal Infections / Q000382:microbiology*; D041121:Klebsiella oxytoca / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011513:Proteus mirabilis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012705:Serratia / Q000187:drug effects; D000078142:Tazobactam; D014481:United States; D014552:Urinary Tract Infections / Q000382:microbiology*; D018440:beta-Lactam Resistance / Q000187:drug effects; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C000594038:ceftolozane, tazobactam drug combination; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam
Ceftolozane/tazobactam; ESBL; Pseudomonas aeruginosa; Urinary tract infections