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Purpose: To evaluate the real-world evidence of ceftazidime-avibactam (CAZ-AVI) compared to intravenous colistin for the treatment of multidrug-resistant (MDR) P. aeruginosa infections. Method: This is a multicenter, retrospective cohort study conducted in the period between 2017 and 2023 at five institutions for patients who received either CAZ-AVI or colistin-based regimens for treating MDR P. aeruginosa infections. Outcomes were compared using multivariate logistic regression analysis. Result: Among the screened patients, 203 patients were included: 89 in the CAZ-AVI group and 114 in the colistin group. A total of 57% presented with pneumonia, 21% with bacteremia, and 61% were in the intensive care unit. The rate of clinical cure was significantly higher among patients who received CAZ-AVI (67% vs. 50%; OR, 2.07; 95% CI, 1.16–3.68). The rate of in-hospital mortality was numerically lower among patients who received CAZ-AVI (40% vs. 49%; OR, 0.58; 95% CI, 0.33–1.03). The rate of AKI was significantly lower among patients who received CAZ-AVI (15% vs. 43%; OR, 0.23; 95% CI, 0.11–0.45). Conclusion: CAZ-AVI was more effective in treating MDR P. aeruginosa infections and showed a better safety profile compared to colistin. Thus, CAZ-AVI could be a better alternative for treating MDR P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the safety and effectiveness of monotherapy versus combination therapy for the treatment of infections caused by S. maltophilia. Methods: This retrospective, multicenter, cohort study included patients treated with either monotherapy or combination therapy for infections caused by S. maltophilia. Primary outcomes included overall in-hospital mortality, 30-day mortality, and clinical cure. Safety outcomes were also evaluated. Multivariable logistic regression was used as a control for confounding variables. Results: A total of 407 patients were included, 330 patients received monotherapy and 77 patients received combination therapy. A total of 21% presented with concomitant bacteremia. After adjusting the differences between the two groups, there were no statistically significant differences between patients who received monotherapy versus combination therapy in clinical cure (55% vs 65%; OR, 0.72; 95% CI, 0.40–1.31) and overall in-hospital mortality (52% vs 49%; OR, 0.84; 95% CI, 0.45–1.57). However, patients who received monotherapy had a lower rate of 30-day mortality (28% vs 32%; OR, 0.45; 95% CI, 0.22–0.90) and acute kidney injury (9% vs 18%; OR, 0.35; 95% CI, 0.16–0.78). Conclusion: Clinical outcomes did not significantly differ in patients who received combination therapy versus monotherapy. More data are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Obesity combined with critical illness might increase the risk of acquiring infections and hence mortality. In this patient population the pharmacokinetics of antimicrobials vary significantly, making antimicrobial dosing challenging. The objective of this study was to assess the predictive performance of published population pharmacokinetic models of vancomycin in patients who are critically ill or obese for a cohort of critically ill patients who are obese. This was a multi‐center retrospective study conducted at 2 hospitals. Adult patients with a body mass index of ≥30 kg/m2 were included. PubMed was searched for published population pharmacokinetic studies in patients who were critically ill or obese. External validation was performed using Monolix software. A total of 4 models were identified in patients who were obese and 5 models were identified in patients who were critically ill. In total, 138 patients who were critically ill and obese were included, and the most accurate models for these patients were the Goti and Roberts models. In our analysis, models in patients who were critically ill outperformed models in patients who were obese. When looking at the most accurate models, both the Goti and the Roberts models had patient characteristics similar to ours in terms of age and creatinine clearance. This indicates that when selecting the proper model to apply in practice, it is important to account for all relevant variables, besides obesity. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare no conflict of interest.