Novel β-lactam-β-lactamase inhibitors as monotherapy versus combination for the treatment of drug-resistant Pseudomonas aeruginosa infections: A multicenter cohort study

Abstract

BackgroundData comparing the clinical outcomes of novel β-lactam-β-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking. MethodThis retrospective cohort study included patients who received novel β-lactam–β-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. Result118 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. ConclusionNovel β-lactam–β-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.