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Background: People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. Methods: The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Results: Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli, Citrobacter koseri, Proteus mirabilis, and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical ß-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P = .057). Conclusions: C/T treatment was well tolerated and effective in pwCF, including those with previous ß-lactam hypersensitivity.
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Background: This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. Methods: This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. Results: A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. Conclusions: This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.
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OBJECTIVES: To describe the real-world clinical use of ceftolozane/tazobactam (C/T) and associated outcomes in France. PATIENTS AND METHODS: Multicenter, prospective cohort study conducted in 22 hospitals. All adult patients who received at least one dose of C/T were asked to participate (2018-2019). Patients were treated according to standard hospital practice and followed up until C/T stop. RESULTS: At the time of the analysis, 84 patients were evaluated. The median age was 64.8 years, and 67.9% (57/84) of patients were males. Fifty-seven patients (57/82, 69.5%) had one or more risk factors for multidrug-resistant (MDR) infections (missing MDR risk factor data for two patients). Most patients were critically ill and had several comorbidities. A majority (59/84, 70.2%) of patients had nosocomial infections. Half of all patients (n=42) had a diagnosis of pneumonia, of which 69% (29/42) were hospital acquired. Overall, 90.5% (76/84) of patients had MDR bacteria. Pseudomonas aeruginosa was the most frequently isolated bacterium (71/80, 88.8%), including 93% (80/86) of C/T-susceptible strains. C/T was prescribed as the first-line treatment to 29.8% (25/84) of patients. A concomitant antibiotic treatment was prescribed to 48.8% (41/84) of patients, of whom 65.9% (27/41) were prescribed concomitant antibiotics at the same time as C/T initiation. Empirical C/T prescription was microbiologically appropriate in 11/16 patients after susceptibility testing. Most patients (44/72, 61.1%) were cured and four (4/72, 5.6%) deaths were reported. CONCLUSIONS: The results showed that C/T was most frequently prescribed for documented cases of P. aeruginosa infections. Most outcomes were positive, including among pneumonia patients.