Pseudomonas aeruginosa (PA), one of the species of the ESKAPE pathogens that are known to “escape” the effects of many antimicrobials, is often difficult to treat. Ceftolozane-tazobactam (C/T) is an anti-pseudomonal cephalosporin/β-lactamase inhibitor recently approved by FDA and EMEA. We examined its activity against global clinical isolates of PA, including isolates non-susceptible (NS, intermediate or resistant) to other agents.
In 2016, 158 hospitals in 51 countries collected 5533 PA from intra-abdominal (IAI), urinary (UTI), and respiratory tract infections (RTI). MICs were determined using CLSI broth microdilution and interpreted with both CLSI and EUCAST breakpoints, as the susceptible breakpoints for C/T, cefepime (FEP), meropenem (MEM), and piperacillin-tazobactam (P/T) are the same using both criteria.
Overall regional susceptibility of PA to C/T, prevalence of FEP-NS, MEM- NS, and P/T- NS phenotypes, and susceptibility of these phenotypes to C/T are shown below:
Africa | Asia* | Europe | Latin America | Middle East | North America | South Pacific | |
---|---|---|---|---|---|---|---|
All PA (n) | 405 | 795 | 1628 | 759 | 379 | 1137 | 430 |
C/T susceptibility (%) | 87.9 | 89.1 | 90.3 | 85.0 | 89.7 | 94.6 | 97.7 |
PA, FEP-NS [n(% of region total)] | 111 (27.4) | 194 (24.4) | 438 (26.9) | 203 (26.7) | 88 (23.2) | 299 (26.3) | 57 (13.3) |
C/T susceptibility (%) | 56.8 | 55.7 | 66.0 | 45.3 | 59.1 | 80.6 | 84.2 |
PA, MEM- NS [n(% of region total)] | 138 (34.1) | 203 (25.5) | 525 (32.2) | 258 (34.0) | 135 (35.6) | 247 (21.7) | 55 (12.8) |
C/T susceptibility (%) | 68.8 | 62.1 | 72.2 | 58.1 | 72.6 | 82.2 | 85.5 |
PA, P/T- NS [n(% of region total)] | 124 (30.6) | 246 (30.9) | 557 (34.2) | 254 (33.5) | 125 (33.0) | 334 (29.4) | 68 (15.8) |
C/T susceptibility (%) | 66.1 | 69.1 | 73.3 | 57.9 | 69.6 | 82.6 | 86.8 |
* Does not include China or India
Differences in C/T susceptibility across isolates from IAI (91.4%), RTI (90.5%), and UTI (89.3%) were small.
Overall susceptibility to C/T ranged from 85% in Latin America to 98% in South Pacific. FEP-NS, MEM-NS, and P/T-NS isolates were least prevalent in South Pacific. C/T was active against these phenotypes in >80% of isolates in North America and South Pacific and against 62–73% of MEM-NS and P/T-NS isolates in all other regions except Latin America. Monitoring of C/T susceptibility to PA is warranted in light of increasing resistance to first line agents.