Recent studies have shown that shorter-term antibiotic use for children with bacterial pneumonia is efficacious relative to the standard 10-day course. Now, the prospective results of a clinical trial indicate that a more holistic health picture favors shorter durations, as well.
Derek J. Williams, M.D., chief of the Division of Pediatric Hospital Medicine, and Buddy Creech, M.D., Edie Carell Johnson Chair and Professor of Pediatrics at Monroe Carell Jr. Children’s Hospital at Vanderbilt, were co-primary investigators on SCOUT-CAP, a study of 380 children with community-acquired pneumonia across outpatient clinics and emergency settings in eight U.S. cities.
At the end of the three-year study, the researchers concluded that short-course therapy not only equated to standard therapy in treating the illness, but was superior overall.
“A few small studies have looked at this question of five- versus seven-to-10 day courses and found that shorter courses may be effective,” Creech said. “However, this is the first superiority trial to account for both the response to therapy and the potential side effects of the therapy.”
“Children taking the shorter course experienced similar antibiotic side effects, like gastrointestinal discomfort, but we also found their oropharyngeal flora collected a few weeks out had significantly fewer antibiotic-resistance genes,” Williams said. “If we can effectively treat the infection with shorter courses of antibiotics, we can not only eliminate some of these side effects, but we can help reduce antibiotic resistance in both the individual child and globally.”
Patients in the study ranged from 6 months to 6 years in age, with a mean age of 36 months. All had been diagnosed with community-acquired pneumonia and were prescribed outpatient antibiotic treatment. About 90 percent were given amoxicillin, with the remainder given amoxicillin plus clavulanate, or cefdinir. About half the children were randomized to a 10-day course. The other half received a five-day course of antibiotic, after which they received five days of placebo.
“However, this is the first superiority trial to account for both the response to therapy and the potential side effects of the therapy.”
Researchers followed the children closely, and parents kept diaries to record fever and other symptoms. Children with persistent symptoms were referred to their treating provider but were not dropped from the study, even if the duration of antibiotic treatment extended beyond what was initially prescribed.
“Since treatment duration was a component of our outcome, we focused on the duration of antibiotic therapy that was actually received, not the duration that was assigned,” Williams explained. “Some kids prescribed five days may have received additional days of antibiotics due to worsening or persistent symptoms.”
Shorter Course Benefits
Efficacy in terms of symptom resolution, including lingering cough, was equivalent between the groups. A sizable percentage of children had gastrointestinal and other side effects, results that also were similar between groups. However, because children in the short-course group achieved similar outcomes with fewer days of antibiotics, the short course strategy was judged to be superior.
The most novel feature of the study was the antibiotic resistome analysis, completed for a subset of patients between study days 19 and 25. This analysis showed children in the shorter-duration arm of the study had fewer resistance genes per prokaryotic cell, including fewer β-lactamase resistance genes.
In short, the study supports that the five-day course meets efficacy goals, reduces the duration of side effects, lowers the individual child’s development of antibiotic resistance, and reduces the contribution each treatment makes to the global antibiotic-resistance problem.
“If we can effectively treat the infection with shorter courses of antibiotics, we can not only eliminate some of these side effects, but we can help reduce antibiotic resistance in both the individual child and globally.”
Williams says incorporation of shorter duration antibiotics into guidelines may be imminent, though questions remain to be answered about appropriate applications.
“Most of these studies – including SCOUT-CAP – have been done in the outpatient setting, and so have not necessarily extended to those who have more severe pneumonia requiring hospitalization,” he said.
Virus Confounds Progress
Oxygen and antibiotic therapies have pushed bacterial pneumonia mortality rates down, as may the impact of the pneumococcal conjugate vaccine which has become part of routine immunization schedules for children.
Pushing against this progress, however, is the continued prevalence of viral pneumonia, which remains largely intractable. In a pneumonia etiology study of a highly vaccinated population, Williams and colleagues found that about 70 percent of hospitalized children had viral infections.
“We may have lessened the burden of pneumococcus, but clearly viruses play an important role in pneumonia in children,” he said. “Of course, inappropriately giving antibiotics to children with viral infections exacerbates the microbial resistance challenge. We are hoping that shorter courses of antibiotics will do less to interfere with a healthy microbiome for these children, as well as those with bacterial pneumonia.”