A study today in the New England Journal of Medicine finds that shorter antibiotic treatment for infants with ear infections results in worse outcomes than standard-duration treatment and does not reduce levels of antibiotic resistance.
The finding suggests that limiting the duration of antimicrobial treatment for infants with ear infections—the most common condition for which US children receive antibiotics—may be a risky strategy for reducing antibiotic use and slowing the emergence of antimicrobial resistance.
In the prospective, randomized non-inferiority trial, investigators with the University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh assigned 520 children between the ages of 6 and 23 months with acute otitis media to two groups: One that received a 10-day course of amoxicillin-clavulanate (the recommended first-line therapy for ear infections), and one group that received a 5-day course followed by a 5-day course of placebo. Neither the children, parents, or anyone involved in the study knew which treatments the children were receiving. They then assessed the children through phone conversations with the parents and office visits.
During the treatment phase, the investigators assessed the children through phone conversations with the parents and office visits. Parents were also asked to rate their children's scores on the Acute Otitis Media-Severity of Symptoms (AOM-SOS) scale, which consists of seven discrete items—tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever. Higher scores on the scale indicate greater severity of symptoms.
Children in the study were considered to have clinical failure if their symptoms worsened during treatment, otoscopic examination showed a bulging ear drum, or if they did not have complete resolution of ear infection symptoms.
Worse outcomes, no difference in antibiotic resistance rates
Overall, the investigators found that the risk of treatment failure was more than twice as great in the children who received a 5-day regimen of antibiotics as in those who received the 10-day treatment, with 34% in the 5-day group showing clinical failure and only 16% in the 10-day group showing failure. The 17 percentage point difference exceeded the pre-specified 10 percentage point non-inferiority margin.
Symptoms also appeared to worsen more among the children who received the shorter course of antibiotics. The children in the shorter-duration group scored higher on the AOM-SOS scale in the day 6 to day 14 assessment (mean symptom score 1.61, compared to 1.34 in the 10-day group) and in the day 12 to day 14 assessment (1.89 versus 1.20).
In addition, the investigators observed no significant differences between the two groups in the rates of adverse events (such as diarrhea), recurrence of otitis media, or antimicrobial resistance. In both groups, nasopharyngeal colonization with penicillin-nonsusceptible pathogens was roughly the same.
"The results of this study clearly show that for treating ear infections in children between 9 and 23 months of age, a 5-day course of antibiotic offers no benefit in terms of adverse events or antibiotic resistance," lead study author Alejandro Hoberman, MD, chief of the division of general pediatrics at Children's Hospital of Pittsburgh, said in a hospital news release. "Though we should be rightly concerned about the emergence of resistance overall for this condition, the benefits of the 10-day regimen greatly outweigh the risks."
The 10-day regimen was so superior to the 5-day regimen that an independent board overseeing the trial decided to end it prematurely.
Hoberman and his colleagues write that their study was intended to address some methodological gaps in previous studies, which have shown either no difference in outcome between the two treatment options or small differences that favored 10-day treatment.
Antibiotics and ear infections
David Hyun, MD, senior officer with the Pew Charitable Trusts' antibiotic resistance project and a pediatric infectious diseases specialist, says the study provides a lot of "good and sound" results on the efficacy of shorter duration antibiotic treatments for ear infections. While it is only a single-center study, he says, the size and comprehensiveness of the study makes it a significant addition to the literature on the topic.
"It provides some strong evidence suggesting a shorter course of antibiotics for ear infections in this age group is potentially more harmful," Hyun told CIDRAP News, adding that the findings will likely be taken into consideration when guidelines for treatment of ear infection in children are next reviewed.
Under current American Academy of Pediatrics (AAP) guidelines, physicians are advised to prescribe antibiotics for children 6 months or older with severe signs or symptoms of unilateral or bilateral acute otitis media. But based on joint decision-making with parents, clinicians can offer observation with close follow-up for 2 to 3 days in children 6 months or older if the symptoms are unilateral and non-severe. This "watchful waiting" approach was among changes that were made by the AAP in 2009 to rein in antibiotic prescribing for ear infections.
While acute otitis media can be caused by bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, it can also be caused by viruses. Ear infections caused by viruses will not improve with antibiotics.
Katherine Fleming-Dutra, MD, of the Center for Disease Control and Prevention says that while shorter antibiotic regimens have been found to work just as well as longer courses in some conditions, such as urinary tract infections and pneumonia, "every infection is different."
"We really need high-quality studies that are designed to answer the question of what is the ideal length of antibiotic therapy for specific diagnoses…and specific populations," Fleming-Dutra told CIDRAP News. This study, she said, will help inform providers treating children with acute otitis media for whom antibiotics are recommended.
The authors say their findings cannot be generalized to children older than those included in the study.
Dec 22 N Eng J Med abstract
Dec 21 Children's Hospital of Pittsburgh press release