fr-264205 and Bacteremia

Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard treatments, especially for bacteremia caused by resistant pathogens, a systematic literature review (SLR) was conducted to understand the utilization of ceftolozane/tazobactam (C/T) in bacteremia.. Most studies were observational (k = 20 studies), though few interventional studies were also identified (k = 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n = 1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k = 6, reported range: 33.3% to 100%; secondary bacteremia: k = 8, 60% to 100%; mixed/unspecified bacteremia: k = 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k = 3, all reporting 100%; secondary: k = 4, 68% to 80%; mixed/unspecified: k = 5, 60% to 80%). Thirteen studies reported mortality (primary: k = 4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k = 7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay.. Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.

Topics: Anti-Bacterial Agents; Bacteremia; Cephalosporins; Communicable Diseases; Humans; Tazobactam

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.. 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.. 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.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Continuous Renal Replacement Therapy; Female; Humans; Male; Retrospective Studies; Tazobactam

Ceftolozane-tazobactam is an emerging ‎treatment for severe infections caused by multidrug-resistant (MDR) Pseudomonas ‎aeruginosa. However, limited ‎data support its use in bacteremia treatment. This study aimed to assess the effectiveness of the treatment of MDR P. aeruginosa bacteremia using ceftolozane-‎tazobactam-based or colistin-based regimens. ‎ PATIENTS AND METHODS: This retrospective, cohort, multicentre study included adult patients with ‎MDR P. aeruginosa bacteremia treated with either ceftolozane-tazobactam or ‎colistin, between September 2018 and August 2021, at four hospitals in Saudi ‎Arabia. The primary endpoint was the 30-day risk-adjusted mortality. Secondary endpoints included the 14-day risk of mortality, bacterial eradication, and clinical ‎success. Cox proportional hazards ‎regression and relative risk estimation were used for analysis, as appropriate. ‎ RESULTS: In total, 46 patients were included; 17 patients received ceftolozane-‎tazobactam-based regimen, and 29 received a colistin-based regimen. There was no association with the use of ‎ceftolozane-tazobactam compared to colistin and the 30-day risk-adjusted mortality ‎‎(hazard ratio [HR] ‎0.58, 95% confidence interval [CI] 0.16-2.13, P = 0.42). Also, the ‎‎14-day risk of mortality and bacterial eradication were not different between the ‎ceftolozane-tazobactam and colistin regimens, HR 2.1, 95% CI 0.42-10.48; P = 0.36; and ‎relative risk (RR) 0.65; 95% CI 0.28-1.52; P = 0.30; respectively. On the other hand, ‎ceftolozane-tazobactam use was associated with higher clinical success than colistin ‎‎(RR 1.84, 95% CI 1.11-3.06: P = 0.021).‎ CONCLUSION: The risk of mortality of MDR P.aeruginosa bacteremia was ‎similar when treated with ceftolozane-tazobactam-based or colistin-based antimicrobial regimens. A higher clinical success was observed with the ceftolozane-‎tazobactam-based regimen compared to the colistin-based regimen. ‎.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Cross Infection; Healthcare-Associated Pneumonia; Humans; Pharmaceutical Preparations; Polymyxins; Pseudomonas aeruginosa; Tazobactam; Treatment Outcome

Ceftolozane/tazobactam is a novel antibiotic approved for the treatment of complicated intra-abdominal and complicated urinary tract infections.. We describe the use of off-label ceftolozane/tazobactam in the management of a multidrug-resistant Pseudomonas aeruginosa bacteremia that was already being treated with colistin and amikacin, the only active antibiotics according to the antibiogram.

Topics: Anti-Bacterial Agents; Bacteremia; Cephalosporins; Drug Resistance, Multiple, Bacterial; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Off-Label Use; Penicillanic Acid; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P. aeruginosa bloodstream infection in a pediatric leukemia patient with ceftolozane/tazobactam and provides the first description of its pharmacokinetics in pediatrics.

Topics: Anti-Bacterial Agents; Bacteremia; Cephalosporins; Child; Drug Resistance, Multiple, Bacterial; Hospitalization; Humans; Leukemia; Male; Penicillanic Acid; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam