Study: Azithromycin overprescribed for kids' pneumonia

Combination antibiotic treatment for community-acquired pneumonia in children is common, but a new study suggests that using just one of the two drugs is just as effective in most cases and can go a long way toward curbing the use of azithromycin, one of the most commonly used antibiotics in pediatric settings.

A research team based at Vanderbilt University Medical Center (VUMC) reported their findings in a recent issue of JAMA Pediatrics.

For most pneumonia infections, the causative agent is difficult to identify, and clinicians often prescribe empiric treatment. Amoxicillin, a beta lactam drug, treats the most common bacteria that cause pneumonia and according to national guidelines is the treatment of choice for most children with the disease.

Azithromycin, a macrolide antibiotic, is often used to treat "atypical pneumonia," which can be more common in older children and adolescents, though the benefits of the drug aren't clear.

Of patients, 28% got combo drugs

The prospective observational study, part of a larger pneumonia etiology study, included 1,418 children hospitalized at three centers in Tennessee and Utah from January 2010 to June 2012 for radiologically confirmed pneumonia; 72% received just amoxicillin, while 28% were treated with both amoxicillin and azithromycin.

Nearly 74% of the kids had a virus detected, with or without bacterial coinfection. Atypical pathogens were found in nearly 9% of children, 95.2% of which was Mycoplasma pneumoniae.

Comparing the clinical courses of the two treatment groups, researchers found no significant differences in length of stay, intensive care unit (ICU) admission, readmission, or recovery at follow-up appointments.

They also didn't find any significant differences when they looked at subgroups of children most likely to benefit from combination therapy, including those with Mycoplasma pneumoniae, those with wheezing, and those admitted to ICUs.

Big target for antibiotic stewardship

Derek Williams MD, MPH, the study's lead author and assistant professor of pediatrics at VUMC, said in a Vanderbilt press release that combination therapy with azithromycin is unnecessary in most cases of pediatric pneumonia, because the bacteria targeted by the drug are less common than other pneumonia causes, including viruses, and that its effectiveness hasn't been clearly shown in earlier studies.

Pneumonia accounts for more antibiotic days in US children's hospitals than any other condition, he said, making its treatment a big target for antimicrobial stewardship efforts. "Reducing unnecessary antibiotic use in pediatric pneumonia and other respiratory illnesses is one strategy to help slow the progression of antimicrobial resistance."

Williams said, however, that identifying which children with pneumonia may benefit from macrolide antibiotics like azithromycin is urgently needed.

Carlos Grijalva, MD, MPH, the study's senior author and associate professor of health policy at VUMC, added that the findings also point to a need to characterize the most common pneumonia pathogens and the effectiveness of antibiotic regimens to better guide empiric treatment.

'Healthy skepticism' for routine azithromycin

In an editorial in the same issue, Michael Smith, MD, MSCE, with the division of pediatric infectious diseases at Duke University, said the study findings challenge the standard of care for children with pneumonia. He pointed out that azithromycin is one of the most commonly used antibiotics in pediatrics and was prescribed to 12.2 million outpatients in 2013, making up 20% of all antibiotic prescriptions for kids in ambulatory settings.

Community-acquired pneumonia is one of the few pediatric indications for macrolides, and he said in children's hospitals, about one-third of kids hospitalized with the illness are treated with them.

Though in vitro studies have shown macrolides to be active against two common causes of atypical pneumonia—Chlamydophila pneumoniae and M pneumoniae—systematic reviews didn't find enough evidence to draw meaningful conclusions. "Nevertheless, they are now the standard of care," he said regarding treatment for hospitalized kids for whom atypical pneumonia is an important consideration.

Some of the studies used to support macrolides for treating pediatric pneumonia were based on administrative claims that showed shorter hospital stays in children treated with the antibiotic combination, Smith said.

The new study, though, allows for a more specific definition of pneumonia that included radiographic evidence, lab test results, and physical exam findings, Smith wrote.

Though a larger prospective study might have the potential to tease out differences between monotherapy and combination therapy, "at the end of the day, it is hard to get around the fact that there was no benefit among 125 children with radiologically confirmed pneumonia and positive test results for atypical bacteria," he said.

Smith added that there are clearly cases for which macrolides are needed, "but we should approach routine azithromycin use with a healthy skepticism."

See also:

Oct 30 JAMA Pediatr abstract

Oct 30 JAMA Pediatr editorial

Nov 1 VUMC press release

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