No lung benefit with double IV antibiotic strategy for pediatric pulmonary exacerbations

Use of two IV antipseudomonal antibiotics was not associated with improvement in clinical outcomes compared with one IV and one inhaled antibiotic in young patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection.

“The standard approach for people with cystic fibrosis and P. aeruginosa infection when you’re trying to treat for [pulmonary] exacerbations is to use two IV antipseudomonal antibiotics, even though there is limited evidence to support this,” Jonathan Cogen, MD, MPH, attending physician in the division of pulmonary and sleep medicine in the department of pediatrics at the University of Washington, Seattle, said during a presentation at the virtual North American Cystic Fibrosis Conference. “The idea is that perhaps it can reduce some antimicrobial resistance.”

Cogen and colleagues aimed to determine whether use of two IV antipseudomonal antibiotics would be associated with improved clinical outcomes compared with use of one IV antipseudomonal antibiotic, with or without the addition of an inhaled antibiotic.

The retrospective cohort study included 3,294 children and adolescents with cystic fibrosis who had a hospitalization from 2007 to 2018 and were aged 6 to 21 years at discharge. Patients were culled from the CF Foundation Patient Registry-Pediatric Health Information System data set. Chronic P. aeruginosa infection was defined as having a P. aeruginosa positive respiratory culture in at least two age quarters over 2 years. Exposures were defined as treatment in at least 80% of hospital days.

Clinical outcomes were pre- to post-pulmonary exacerbation change in lung function, recovery to baseline lung function (> 90%) and time to next pulmonary exacerbation requiring IV antibiotics.

The researchers assessed 3,428 pulmonary exacerbations in this cohort. The most common antibiotic exposure group was two IV antipseudomonal antibiotics with no inhaled antibiotic (n = 1,690), followed by two IV antipseudomonal antibiotics and one inhaled antibiotic (n = 433). Those who received one IV antipseudomonal antibiotic tended to be sicker than those who received two IV antipseudomonal antibiotics; this group also had lower baseline lung function and more pulmonary exacerbations in the previous year, Cogen said.

Researchers observed no difference in pre- to post-pulmonary exacerbation change in lung function between the groups: median change, 9.3 in the group that received one IV antibiotic; 10.3 in the group that received one IV antibiotic and one inhaled antibiotic; 11.4 in the group that received two IV antibiotics; and 12.1 in the group that received two IV antibiotics and one inhaled antibiotic. Mean difference in pre- to post-pulmonary exacerbation change in lung function was 0.45% in the group that received two IV antibiotics compared with those who received one IV and one inhaled antibiotic (P = .61) and –1.7% in the group that received one IV antibiotic compared with those who received two IV antibiotics (P = .067).

Odds of recovery to baseline lung function was 1.04 (95% CI, 0.65-1.64) among those treated with two IV antibiotics compared with those treated with one IV antibiotic and one inhaled antibiotic (P = .88) and 0.83 (95% CI, 0.57-1.2) among those treated with one IV antibiotic compared with those treated with two IV antibiotics (P = .32).

“There is no increased odds of returning to [baseline] lung function among people treated with two IV antipseudomonals compared with people treated with one IV antipseudomonal with or without the addition of an inhaled antibiotic,” Cogen said.

For time to next pulmonary exacerbation requiring IV antibiotics, the researchers reported a 31% increased risk in those who received one IV antibiotic and one inhaled antibiotic compared with those treated who received two IV antibiotics and no inhaled antibiotics (HR = 1.31; 95% CI, 1.06-1.63; P = .014). There was no difference in the group that received one IV antibiotic and no inhaled antibiotic, Cogen said.

According to Cogen, limitations of this study included the inability to adjust for indication bias, exclusion of people with lung function drops of less than 3%, and exclusion of home IV antibiotics and adults.

“Compared to treatment with two IV antipseudomonals, the use of one IV antipseudomonal antibiotic with or without one inhaled antibiotic was not associated with improvement in any of the lung function outcomes. But, among pulmonary exacerbations treated with one IV and one inhaled [antibiotic], there was a 31% increased hazard for future exacerbations requiring IV antibiotics compared with treatment with two IV antipseudomonals.

“Future studies are clearly needed. This is not a study you can hang your hat on, but I think it’s an intriguing study with intriguing results, and it brings the question [of] whether we need to expose our patients to all these extra antibiotics when perhaps they’re not actually leading to improved outcomes.”