Intravenous (IV) antibiotic therapy did not confer a significantly increased benefit compared with oral antibiotics as eradication therapy for pulmonary infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis, according to results of a phase 4, multicenter, parallel-group, randomized controlled trial published in Health Technology Assessment.
Between October 2010 and January 2017, investigators enrolled patients older than 28 days with cystic fibrosis who either had no history of a P aeruginosa infection or who had been infection free for at least 1 year. Patients were randomly assigned in a 1:1 fashion to receive either IV ceftazidime 150 mg/kg/day plus tobramycin 10 mg/kg/day for 14 days, or oral ciprofloxacin 20 mg/kg twice daily for 3 months. Of note, patients younger than 5 years in the oral antibiotic treatment group were given oral ciprofloxacin at a dose of 15 mg/kg twice daily. In addition, patients in both groups also received treatment with inhaled colistimethate sodium for 3 months. The primary outcome, using an intention-to-treat analysis, was the eradication of P aeruginosa at 3 months and remaining free of infection after 15 months. Investigators also conducted a safety analysis of patients who received at least 1 dose of any study drug, and a cost-effectiveness analysis to determine the cost per eradication and per quality-adjusted life-years. Patients completed the cystic fibrosis questionnaire (CFQ) and EuroQol-5 Dimensions health utility questionnaire at baseline, and at 3, 15, and 24 months.
Among a total of 286 patients included in the study, 137 were in the IV antibiotics group and 149 were in the oral antibiotics group. In addition, the majority of patients (54%) in both groups were men (54%) and aged between 2 and 11 years.
The investigators noted that 44% and 52% of patients in the IV antibiotics and oral antibiotics group achieved the primary outcome, respectively. Although patients in the IV antibiotics group were less likely to achieve the primary outcome vs those in the oral antibiotics group, the difference was not statistically significant (relative risk [RR], 0.84; 95% CI, 0.65-1.09; P =.184). A post-hoc analysis showed that patients in the IV antibiotics group were at a significantly increased risk for the unsuccessful eradication of P aeruginosa infection after 3 months of treatment (RR, 2.74; 95% CI, 1.01-7.44; P =.037).
In a 12-month period following eradication therapy, the investigators found that the rate of hospitalization was significantly decreased among patients in the IV antibiotics group vs those in the oral antibiotics group (RR, 0.69; 95% CI, 0.5-0.95; P =.02). Of note, most patients in the IV antibiotics group had been hospitalized at baseline.
The investigators performed a safety analysis and found that a total of 32 severe adverse events occurred in 24 patients, 10 of whom were in the IV antibiotics group and 14 were in the oral antibiotics group.
Oral antibiotic therapy was more cost-effective compared with intravenous antibiotic therapy, with a total cost savings equivalent to $7543.00. The investigators noted that the increased costs associated with IV antibiotics were likely due to the increased risk for hospitalization.
This study was limited by the small number of adults included in the study (n=15), and by the possibility that the study population may have had a better clinical status than those with cystic fibrosis in the general population.
Given the cost-effectiveness of oral antibiotic eradication therapy, the investigators noted that “when the findings of this trial are implemented in routine clinical practice, most patients will receive oral [antibiotic] treatment as an outpatient and many [hospital] admissions will be avoided.” They concluded that the implementation of these findings in clinical practice “…will [decrease] [both the] treatment burden and [associated] healthcare costs.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Langton Hewer SC, Smyth AR, Brown M, Jones AP, Hickey H, Kenna D, et al. Intravenous or oral antibiotic treatment in adults and children with cystic fibrosis and Pseudomonas aeruginosa infection: the TORPEDO-CF RCT. Health Technol Assess. 2021;25(65). doi:10.3310/hta25650