Clinical Outcomes of Ceftazidime-Avibactam versus Ceftolozane-Tazobactam in Managing Pseudomonal Infections in Patients Undergoing Renal Replacement Therapy.

The optimal doses of ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) for treating multidrug-resistant (MDR) Pseudomonas aeruginosa (PSA) in patients utilizing renal replacement therapy (RRT) are not well established. Hence, the objective of this study is to evaluate the clinical outcomes associated with the suggested doses of CZA and C/T in patients with PSA infection utilizing RRT. METHODS: This is a retrospective study conducted at our hospital between September 2018 and March 2022. Clinical cure was the primary endpoint, while microbiologic cure, 30-day recurrence, and 30-day mortality were the secondary endpoints. RESULTS: In total, 45 subjects met the inclusion criteria, with 25 receiving CZA and 20 receiving C/T. The median age was 69 (52-81) and 69 (61.5-83) years, respectively, while the median weight was 70 (55.5-81.5) and 66 (57-79) kg, respectively. Clinical cure was achieved in 12 (48%) subjects in the CZA group and 12 (60%) in the C/T group (p = 0.432). Of the 36 subjects who had repeated cultures, a microbiologic cure was achieved in 14/23 (60%) subjects and 10/13 (76.9%) subjects (p = 0.273). Thirty-day recurrence was reported in 3 (12%) cases in the CZA group and 6 (30%) in the C/T group (p = 0.082). The 30-day mortality was 13 (52%) subjects in the CZA group and 10 (50%) in the C/T group (p = 0.894). The median maintenance dose of CZA was 1.88 (0.94-3.75) g and 2.25 (1.5-2.25) g for C/T. Multivariate logistic regression analysis indicated that both drugs did not differ significantly in clinical cure. Bloodstream infection (BSI) (OR = 25, 95% CI: 1.63-411.7, p = 0.021) was the only independent factor associated with clinical cure in this population. CONCLUSIONS: Our findings indicated that C/T and CZA did not significantly differ in achieving clinical cure in patients with MDR PSA infections undergoing RRT. Larger clinical trials are needed to confirm our findings.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

Ceftolozane-tazobactam (C/T) recommended dosing in patients undergoing renal replacement therapies (RRT) is lacking evidence. The objective of this study was to evaluate the clinical outcomes of C/T dosing in patients on RRT. MATERIALS AND METHODS: A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. RESULTS: Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. CONCLUSION: The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

Microbiologic outcomes of ceftazidime-avibactam dosing in patients with sepsis utilizing renal replacement therapies.

INTRODUCTION: The suggested dose of ceftazidime-avibactam (CEF/AVI) in patient with multidrug resistant organisms and utilizing renal replacement therapies (RRTs) is not validated in clinical studies. The objective of this study was to evaluate the microbiologic cure of bacteremia and pneumonia using the recommended CEF/AVI dosing in patients utilizing RRT. METHODS: A retrospective observational study conducted at our institution between September 15, 2018 and March 15, 2022. The primary end point was to determine the microbiologic cure. The secondary end points were the clinical cure, 30-day recurrence, 30-day all cause mortality. RESULTS: Fifty-six patients met the inclusion criteria, 36 (64.3%) were males, the median age was 69 (59.5-79.3) years, and the median weight was 69 (60-83.8) kg. Pneumonia represented 34 (60.7%) of infections. Microbiologic cure was achieved in 32 (57%) subjects. However, clinical cure was achieved in 23 (71.9%) patients in the microbiologic cure group versus 12 (50%) in the microbiologic failure group (p = 0.094). The 30-day recurrence occurred in 2 (6.3%) patients in the microbiologic cure group versus 3 (12.5%) in the microbiologic failure group (p = 0.673). Further, the 30-day all-cause mortality was 18 (56.3%) versus 10 (41.7%) in both groups respectively (p = 0.28). The most used dose in patients utilizing continuous veno-venous hemofiltration (CVVH) was 1.25 g q8h, while the dose was 1.25 g q24h in those who utilized intermittent hemodialysis (IHD). The multivariate logistic regression indicated that bacteremia (OR 41.5 [3.77-46]), Enterobacterales (OR 5.4 [1.04-27.9]), and the drug daily dose (OR 2.33 [1.15-4.72]) were independently associated with microbiologic cure. CONCLUSION: Microbiologic cure of ceftazidime-avibactam in patient utilizing CVVH and IHD is dependent on bacteremia diagnosis, the drug daily dose, and bacterial species. These findings need to be replicated in a larger prospective study, with no recommendations in those utilizing RRT.