RESUMO
BACKGROUND: Data comparing the clinical outcomes of novel ß-lactam-ß-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking. METHOD: This retrospective cohort study included patients who received novel ß-lactam-ß-lactamase inhibitors as monotherapy or in combination for the treatment of MDR P. aeruginosa infections. The study was conducted between 2017 and 2022 in 6 tertiary care hospitals in Saudi Arabia. Overall in-hospital mortality, 30-day mortality, clinical cure, and acute kidney injury (AKI) were compared between recipients of monotherapy versus combination using multivariate logistic regression analysis. RESULT: 118 patients and 82 patients were included in monotherapy and combination therapy arms, respectively. The cohort represented an ill population with 56% in the intensive care unit and 37% in septic shock. A total of 19% of patients presented with bacteremia. Compared to monotherapy, combination therapy did not significantly differ in clinical cure (57% vs. 68%; P = 0.313; OR, 0.63; 95% CI, 0.36-1.14) in-hospital mortality (45% vs. 37%; P = 0.267; OR, 1.38; 95% CI, 0.78-2.45), or 30-day mortality (27% vs. 24%; P = 0.619; OR, 1.18; 95% CI, 0.62-1.25). However, AKI (32% vs. 12%; P = 0.0006; OR, 3.45; 95% CI, 1.67-7.13) was significantly more common in patients who received combination therapy. CONCLUSION: Novel ß-lactam-ß-lactamase inhibitors when used in combination with other antibiotics did not add clinical benefit compared to their use as monotherapy in the treatment of MDR P. aeruginosa infections. A Combination regimen was associated with an increased risk of nephrotoxicity.
RESUMO
Ceftolozane-tazobactam (C-T) and ceftazidime-avibactam (CAZ-AVI) are two novel antimicrobials that retain activity against resistant Pseudomonas aeruginosa. The comparative effectiveness and safety of C-T versus CAZ-AVI remain unknown. A retrospective, multicenter cohort study was performed in six tertiary centers in Saudi Arabia and included patients who received either C-T or CAZ-AVI for infections due to multidrug-resistant (MDR) P. aeruginosa. Overall in-hospital mortality, 30-day mortality, and clinical cure were the main study outcomes. Safety outcomes were also evaluated. A multivariate analysis using logistic regression was used to determine the independent impact of treatment on the main outcomes of interest. We enrolled 200 patients in the study (100 in each treatment arm). A total of 56% were in the intensive care unit, 48% were mechanically ventilated, and 37% were in septic shock. Approximately 19% of patients had bacteremia. Combination therapy was administered to 41% of the patients. The differences between the C-T and CAZ-AVI groups did not reach statistical significance in the overall in-hospital mortality (44% versus 37%; P = 0.314; OR, 1.34; 95% CI, 0.76 to 2.36), 30-day mortality (27% versus 23%; P = 0.514; OR, 1.24; 95% CI, 0.65 to 2.35), clinical cure (61% versus 66%; P = 0.463; OR, 0.81; 95% CI, 0.43 to 1.49), or acute kidney injury (23% versus 17%; P = 0.289; OR, 1.46; 95% CI, 0.69 to 3.14), even after adjusting for differences between the two groups. C-T and CAZ-AVI did not significantly differ in terms of safety and effectiveness, and they serve as potential options for the treatment of infections caused by MDR P. aeruginosa.
