We evaluated the activity of ceftolozane/tazobactam (C/T), and comparators against clinical Pseudomonas aeruginosa isolates collected for the global Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in ten countries in the Middle East and Africa to augment scarce standardized surveillance data in this region. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute broth microdilution and interpreted with European Committee on Antimicrobial Susceptibility Testing breakpoints. P. aeruginosa isolates testing with C/T MIC >4 mg/l or imipenem MIC >2 mg/l were screened for β-lactamase genes. C/T was active against 91.4% and 87.0% of P. aeruginosa isolates from the Middle East and Africa, respectively (14-21 and 7-16 percentage points higher than most β-lactam comparators, respectively). Considerable variation in susceptibility was seen across countries, which largely correlated with the observed prevalence of carbapenemases and/or extended-spectrum β-lactamases. Differences across countries were smaller for C/T than for the β-lactam comparators, ranging from 81% C/T-susceptible among isolates from Jordan to 95% for Qatar. Among subsets resistant to meropenem, ceftazidime, or piperacillin/tazobactam, C/T maintained activity against 51-73% of isolates from the Middle East and against 27-54% from Africa (where metallo-β-lactamase and GES carbapenemase rates were higher). Given the desirability of β-lactam use among clinicians, C/T represents an important option in the treatment of infections caused by P. aeruginosa.

Objectives: To describe annual trends in the susceptibility of clinical isolates of Pseudomonas aeruginosa from Latin America to ceftolozane/tazobactam. Methods: The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program collected 10,188 P. aeruginosa isolates from 57 unique clinical sites in 12 Latin American countries from 2016 to 2024. MICs were determined by reference broth microdilution testing and interpreted using 2025 CLSI M100 breakpoints. Results: Overall, 86.3% of clinical isolates of P. aeruginosa collected in Latin America were susceptible to ceftolozane/tazobactam, including 45.5% of multidrug-resistant (MDR) isolates. From 2016 to 2024, annual percent susceptible values for ceftolozane/tazobactam ranged from 84.9% (2016, n = 779) to 89.2% (2023, n = 1144), with a statistically significant linear trend for increasing susceptibility (p = 0.024; Cochran–Armitage test for trend). However, limiting analysis solely to the 14 clinical sites, from six countries, that participated in each of the nine years (n = 4565) indicated that the annual percent susceptible values for ceftolozane/tazobactam remained unchanged from 2016 (82.6%) to 2024 (83.9%) (p = 0.367; percent susceptible value range, 82.6 to 89.1%). Every year, from 2016 to 2024, all P. aeruginosa isolates from pediatric patients (<18 years of age) were consistently more susceptible to ceftolozane/tazobactam than those from adult patients (90.3 to 95.0%/year versus 83.3 to 88.6%/year, respectively). Significant variation (p < 0.05) in annual ceftolozane/tazobactam percent susceptible values was not observed for isolates from blood, intra-abdominal, and respiratory tract sources, while isolates from urine showed a trend of increasing ceftolozane/tazobactam susceptibility from 73.1% (2018, n = 145) to 90.6% (2023, n = 117) (p < 0.0001). Among individual countries that participated each year, P. aeruginosa isolates from all except Guatemala displayed stable or increasing rates of susceptibility to ceftolozane/tazobactam. Conclusions: Since it was first tested by the SMART program in 2016, and for 8 years thereafter, the in vitro activity of ceftolozane/tazobactam has remained consistent against clinical isolates of P. aeruginosa from the Latin American region (overall, 86.3% susceptible), with limited resistance development restricted to specific clinical sites.

Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with substantial morbidity, mortality and therapeutic uncertainty, particularly in critically ill and immunocompromised patients. Imipenem/cilastatin/relebactam (IMI/REL) combines the established carbapenem imipenem with cilastatin, a dehydropeptidase-I inhibitor, and relebactam, a diazabicyclooctane beta-lactamase inhibitor that restores imipenem activity against selected class A and class C beta-lactamase-mediated resistance mechanisms. Methods: A targeted narrative review was undertaken to identify and provide an overview of published observational studies and conference abstracts reporting clinical outcomes with IMI/REL in patients with confirmed or suspected MDR P. aeruginosa infection. Evidence was summarized descriptively, because the available studies were heterogeneous in design, infection site, patient severity, pathogen mix, susceptibility testing and outcome definitions. Results: Real-world IMI/REL data remain limited but are increasingly informative. IMI/REL was commonly used in high-risk patients, including those with pneumonia, bacteremia, intensive care admission, prior antimicrobial exposure, polymicrobial infection or limited alternative treatment options. Reported clinical success or clinical cure was observed in approximately 56–70.2% of patients, although interpretation is limited by non-comparative designs, small patient populations and mixed-pathogen populations. Thirty-day all-cause mortality varied widely, broadly reflecting baseline severity, infection site and salvage-therapy use. Emergence of IMI/REL non-susceptibility was variably reported, but some recent studies report high rates of treatment-emergent resistance; this requires caution and remains an important area for surveillance. Conclusions: IMI/REL appears to be a clinically useful option for susceptible MDR P. aeruginosa infections, particularly in patients with limited alternatives. Available real-world evidence should be interpreted cautiously, because most data derive from retrospective uncontrolled cohorts.