Antimicrobial activity of ceftolozane/tazobactam tested against Pseudomonas aeruginosa and Enterobacteriaceae with various resistance patterns isolated in European hospitals (2011-12).

To evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against contemporary Gram-negative bacteria. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 10 532 Gram-negative organisms (2191 Pseudomonas aeruginosa and 8341 Enterobacteriaceae) were consecutively collected from 31 medical centres located in 13 European countries plus Turkey and Israel. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A9 document and the results interpreted according to EUCAST as well as CLSI breakpoint criteria. Selected ceftazidime- and/or meropenem-resistant P. aeruginosa isolates were screened for the presence of β-lactamase genes by PCR. P. aeruginosa exhibited high rates of multidrug-resistant (31.9%) and extensively drug-resistant (24.6%) isolates and 11.6% of isolates were susceptible only to colistin. When tested against P. aeruginosa, ceftolozane/tazobactam (MIC(50), 1 mg/L) was generally 4-fold more active than ceftazidime (MIC(50), 4 mg/L) and inhibited >90% of isolates with an MIC of ≤8 mg/L in nine countries. In contrast, the highest susceptibility rates observed for ceftazidime and meropenem, respectively, were 86.0%/86.0% (UK) and 85.2%/86.1% (Ireland) (67.2%/67.1% overall). Ceftolozane/tazobactam (MIC(50/90), 0.25/2 mg/L; 93.7% and 95.2% inhibited at ≤4 and ≤8 mg/L, respectively), meropenem [MIC(50/90), ≤0.06/≤0.06 mg/L; 98.0% susceptible (EUCAST)] and tigecycline [MIC(50/90), 0.12/1 mg/L; 94.1% susceptible (EUCAST)] were the most active compounds tested against Enterobacteriaceae. Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.

Sader HS ，Farrell DJ ，Castanheira M ，Flamm RK ，Jones RN ... -  《-》

Ceftolozane/tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing urinary tract and intraabdominal infections in Europe: report from an antimicrobial surveillance programme (2012-15).

To evaluate the in vitro activity of ceftolozane/tazobactam and comparators tested against European isolates of Enterobacteriaceae and Pseudomonas aeruginosa from hospitalized patients with urinary tract infection or intraabdominal infections. A total of 6553 Gram-negative organisms (603 P. aeruginosa and 5950 Enterobacteriaceae) were consecutively collected from 41 hospitals located in 17 European countries plus Israel and Turkey. The organisms were tested for susceptibility by broth microdilution methods and the results interpreted according to EUCAST and CLSI breakpoint criteria. Ceftolozane/tazobactam [MIC 50/90 0.25/1 mg/L; 93.5%/91.3% susceptible (S) (CLSI/EUCAST criteria)] and meropenem [MIC 50/90  ≤0.06/≤0.06 mg/L; 98.1%/98.3% S (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates, 1.9% were carbapenem resistant (CRE), 15.2% exhibited an ESBL non-CRE phenotype, 14.6% were MDR, 2.2% were XDR and <0.1% were pan-drug resistant (PDR). Whereas ceftolozane/tazobactam showed activity against ESBL non-CRE phenotype isolates (MIC 50/90 0.5/8 mg/L), it lacked useful activity against strains with a CRE (MIC 50/90  >32/>32 mg/L; 3.6% S) or PDR (MIC 50  >32 mg/L; 0.0% S) phenotype. Ceftolozane/tazobactam was the most potent (MIC 50/90 0.5/4 mg/L) β-lactam agent tested against P. aeruginosa isolates, inhibiting 91.7% at an MIC of ≤4 mg/L. P. aeruginosa exhibited high rates of resistance to cefepime (20.6%), ceftazidime (23.1%), meropenem (9.0%) and piperacillin/tazobactam (26.9%) (EUCAST criteria). Among these four P. aeruginosa resistant phenotypes, 61.3%-70.4% were susceptible to ceftolozane/tazobactam. Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.

Pfaller MA ，Bassetti M ，Duncan LR ，Castanheira M ... -  《-》

Ceftolozane/tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in the Asia-Pacific region (minus China, Australia and New Zealand): report from an Antimicrobial Surveillance Pr

The aim of this study was to evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa isolates from patients in the Asia-Pacific (APAC) region with healthcare-associated infections. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 1963 Gram-negative organisms (489 P. aeruginosa and 1474 Enterobacteriaceae) were consecutively collected using a prevalence-based approach from 14 medical centres in the APAC region. Antimicrobial susceptibility testing was performed by broth microdilution method as described by the CLSI and the results were interpreted according to EUCAST and CLSI breakpoint criteria. Ceftolozane/tazobactam [MIC50/90, 0.25/4 µg/mL; 89.2/85.8% susceptible (CLSI/EUCAST)] and meropenem [MIC50/90, ≤0.06/≤0.06 µg/mL; 96.3/96.5% susceptible (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Isolates displayed susceptibility rates to other β-lactam agents ranging from 85.8/81.0% for piperacillin/tazobactam to 74.4/72.7% for cefepime and 72.8/68.1% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates, 3.6% were carbapenem-resistant Enterobacteriaceae (CRE) and 25.6% exhibited an extended-spectrum β-lactamase (ESBL) non-CRE phenotype. Ceftolozane/tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC50/90, 0.5/16 µg/mL), but not against isolates with a CRE phenotype (MIC50/90, >32/>32 µg/mL). Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/4 µg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 90.8% at an MIC of ≤4 µg/mL. Pseudomonas aeruginosa exhibited high rates of susceptibility to amikacin [91.2/89.4% (CLSI/EUCAST)] and colistin [98.4/100.0% (CLSI/EUCAST)]. Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins when tested against Enterobacteriaceae.

Pfaller MA ，Shortridge D ，Sader HS ，Castanheira M ，Flamm RK ... -  《-》

Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012).

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.

Farrell DJ ，Sader HS ，Flamm RK ，Jones RN ... -  《-》

Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2013-2016) as Part of the Surveillance Program: Program to Assess Ceftolozane-Tazoba

Shortridge D ，Pfaller MA ，Castanheira M ，Flamm RK ... -  《-》