May 20, 2022

Oral vs IV antibiotics for Pseudomonas aeruginosa infection in patients with cystic fibrosis

Intravenous (IV) antibiotic therapy did not confer significantly increased benefit over oral antibiotics as a treatment for the eradication of lung infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis, according to the results of a phase 4 randomized controlled trial, multicentre, in parallel groups, published in Health Technology Assessment.

Between October 2010 and January 2017, the researchers recruited patients older than 28 days with cystic fibrosis who had no history of P aeruginosa infected or who had not been infected for at least 1 year. Patients were randomized 1:1 to receive either ceftazidime IV 150 mg/kg/day plus tobramycin 10 mg/kg/day for 14 days, or oral ciprofloxacin 20 mg/kg two times a day for 3 months. It should be noted that patients under 5 years of age in the oral antibiotic treatment group received 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 performed a safety analysis of patients who received at least 1 dose of any study drug, and a cost-effectiveness analysis to determine cost per eradication and per quality-adjusted life years. Patients completed the Cystic Fibrosis Questionnaire (CFQ) and the EuroQol-5 Dimensions Health Status Questionnaire at baseline, and at 3, 15, and 24 months.

Of 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 male (54%) and were between 2 and 11 years old.


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Investigators noted that 44% and 52% of patients in the IV antibiotic and oral antibiotic groups achieved the primary outcome, respectively. Although patients in the IV antibiotic group were less likely to achieve the primary outcome compared to those in the oral antibiotic 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 antibiotic group had a significantly increased risk of unsuccessful eradication of P aeruginosa infection after 3 months of treatment (RR, 2.74; 95% CI, 1.01-7.44; P =.037).

Over a 12-month period following eradication therapy, researchers found that the rate of hospitalization was significantly reduced in patients in the IV antibiotic group compared to those in the oral antibiotic group (RR, 0 .69, 95% CI, 0.5-0.95; P =.02). It should be noted that most patients in the IV antibiotic group had been hospitalized at baseline.

Investigators performed a safety analysis and found that a total of 32 serious adverse events occurred in 24 patients, including 10 in the IV antibiotic group and 14 in the oral antibiotic group.

Oral antibiotic therapy was more cost-effective than intravenous antibiotic therapy, with a total savings equivalent to $7,543.00. The investigators noted that the increased costs associated with IV antibiotics were likely due to the increased risk of 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 had a better clinical condition than people with cystic fibrosis in the general population.

Considering the cost-effectiveness of oral antibiotic eradication therapy, the researchers noted that “when the results of this trial are implemented in routine clinical practice, most patients will receive a [antibiotic] outpatient treatment and many [hospital] admissions will be avoided. They concluded that the implementation of these findings into clinical practice “… [decrease] [both the] burden of treatment and [associated] Health care costs.”

Disclosure: Some study authors have disclosed affiliations with biotechnology, pharmaceutical and/or device companies. Please see the original citation for a full list of author disclosures.

Reference

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 Technology Assessment. 2021;25(65). doi:10.3310/hta25650