Ceftolozane-Tazobactam Versus Ceftazidime-Avibactam for the Treatment of Infections Caused by Multidrug-Resistant Pseudomonas aeruginosa: a Multicenter Cohort Study.

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.

Ceftolozane-tazobactam vs. colistin for the treatment of infections due to multidrug-resistant Pseudomonas aeruginosa: a multicentre cohort study.

OBJECTIVES: The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome. RESULTS: A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T. CONCLUSION: C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

Ceftazidime-avibactam for the Treatment of Multidrug-resistant Pseudomonas aeruginosa Central Nervous System Infection in Pediatric Patient: A Case Report.

Very limited experimental and clinical data are currently available regarding the cerebrospinal fluid (CSF) penetration of ceftazidime-avibactam in adults. Nevertheless, up to our knowledge, there are no data of ceftazidime-avibactam use in central nervous system infections in pediatric patients. For that, here we describe our experience with the use of ceftazidime-avibactam in addition to intraventricular colistin in a pediatric patient diagnosed with ventriculoperitoneal shunt infection due to multidrug-resistant P. aeruginosa. A 2-year-old boy known to pre-term, delivered at 26 weeks with hydrocephalus that required ventriculoperitoneal shunt which was infected due to P. aeruginosa. He was treated with multiple antipseudomonal agents; however, cultures remained persistently positive. On day 54 of admission, the isolate was reported as multidrug-resistant P. aeruginosa and he was switched to ceftazidime-avibactam and intraventricular colistin. CSF cultures became sterile 3 days after initiation of this antibiotic regimen, and subsequent CSF cultures had no growth. No recurrent episode of central nervous system infections due to P. aeruginosa occurred up to 2 years of follow-up.

Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa pneumonia in a patient receiving intermittent hemodialysis.

PURPOSE: The safety and effectiveness of ceftolozane-tazobactam for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa pneumonia in a patient receiving intermittent hemodialysis are reported. CASE REPORT: A 79-year-old African-American man arrived at an emergency trauma center from a nursing home via ambulance with shortness of breath and potential nasogastric tube misplacement. His medical history included end-stage renal disease (ESRD) for which he was receiving intermittent hemodialysis 3 times per week, hypertension, sacral ulcer, coronary artery bypass graft surgery, and P. aeruginosa colonization of his airway. His white blood cell count was elevated, and a chest radiograph revealed atelectasis or infiltrates. As a result, aspiration pneumonia was suggested, and empirical vancomycin and piperacillin-tazobactam were initiated. A few days later, his sputum culture grew MDR P. aeruginosa. Empirical antibiotics were then discontinued, and targeted therapy with ceftolozane-tazobactam i.v. was initiated. A loading dose of ceftolozane-tazobactam 1.5 g i.v. was administered, followed by a maintenance dosage of 300 mg every 8 hours. Following the fifth dose, random ceftolozane-tazobactam plasma concentrations were measured and noncompartmental pharmacokinetics were calculated. After completing a 13-day course of ceftolozane-tazobactam, the patient was discharged from the hospital in stable condition and did not experience any adverse events with ceftolozane-tazobactam. CONCLUSION: In a patient with ESRD receiving intermittent hemodialysis, a ceftolozane-tazobactam loading dose of 1.5 g i.v. followed by a maintenance dosage of 300 mg every 8 hours appeared to be safe and effective in the treatment of nosocomial pneumonia caused by MDR P. aeruginosa.