Antibiotics for Acute Respiratory Tract Infections: Now, Later, or Never?

On average, children in the United States receive more than 1 antibiotic prescription per year, driven largely by acute respiratory tract infections (ARTIs).^1,2  Although most ARTIs are caused by viruses, some are bacterial infections, a subset of which benefit from antibiotics. Identifying the ARTIs that need antibiotics is not always easy. Primary care, urgent care, and emergency medicine clinicians have a hard job.

To address this challenge, the Centers for Disease Control and Prevention outlines multiple approaches to outpatient antibiotic stewardship,³  including delayed antibiotic prescribing, in which a provisional antibiotic prescription is given to a patient or caregiver to fill if symptoms persist or worsen. An example of this approach is acute otitis media (AOM), in which delayed prescribing has been shown to safely reduce antibiotic exposure.⁴ 

In this issue of Pediatrics, Mas-Dalmau et al⁵  report findings from a multicenter, randomized controlled clinical trial comparing antibiotic prescribing strategies for ARTIs in children from 2 to 14 years old presenting to 1 of 39 primary care clinics in Spain. Overall, 436 subjects with AOM, pharyngitis, rhinosinusitis, or acute bronchitis whose provider had “reasonable doubts about the need to prescribe an antibiotic” were assigned to receive immediate, delayed, or no antibiotic therapy. Regardless of the study arm, parents were advised that their child was likely to feel more or less the same for up to 4 days for AOM, 7 days for pharyngitis, 15 days for rhinosinusitis, and 20 days for acute bronchitis; for those in the delayed arm, parents were instructed to give the antibiotic if their child was not better or got worse after the specified number of days. Investigators found no differences in symptom duration or severity (the primary outcomes) across groups; however, antibiotics were, ultimately, taken by only 25% of those given a delayed prescription and 17% of those initially assigned to no antibiotics. Gastrointestinal side effects were worse in those in the immediate antibiotics group, and only 5 subjects had complications, 1 in the delayed group and 2 in each of the other arms. Notably, belief that antibiotics worked was significantly higher for parents of children in the immediate arm than in the other arms, reminding us of the power of what is essentially the antibiotic placebo effect.

These data are reassuring, and the authors should be commended for their efforts to reduce antibiotic overuse, particularly in a region known for relatively high prescribing rates. This work adds to a fairly robust evidence base across populations and conditions. In a Cochrane review of randomized trials including both children and adults, researchers found that, for most ARTIs, delayed prescribing, compared with immediate prescribing, reduced antibiotic use without harm. However, this approach has not been shown to be better than not prescribing antibiotics and re-evaluating (“watchful waiting”), and delayed prescribing passes the responsibility of diagnosis to patients or their caregivers without improving clinical outcomes.⁶ 

But the results of the Mas-Dalmau et al⁵  study might not substantially move the needle. With rare exceptions, children with acute pharyngitis should first receive a group A streptococcal test. If results are positive, all patients should get antibiotics; if results are negative, no one gets them. Acute bronchitis (whatever that is in children) is viral. Acute sinusitis with persistent symptoms (the most commonly diagnosed variety) already has a delayed option,⁷  and the current study (26 children with sinusitis randomly assigned) was not powered for this outcome. We are left with AOM, which dominated enrollment but already has an evidence-based guideline.

So, if delayed prescribing outside of AOM is not prudent, how can pediatricians be better stewards of antibiotics? There are some straightforward answers. Do not prescribe antibiotics when you have enough confidence that the child has a nonbacterial infection, either immediately or delayed. Instead, providing anticipatory guidance about the typical course of a viral infection and which signs or symptoms warrant contacting a clinician are paramount and have shown to be effective: parents want and deserve an explanation and a plan, not necessarily an antibiotic.⁸  Practice “diagnostic stewardship” through application of evidence-based diagnostic criteria for AOM and sinusitis and judicious use of streptococcal testing for pharyngitis. When antibiotics are indicated, choose the narrowest spectrum (penicillin or amoxicillin for most ARTIs) for the shortest effective duration to limit unnecessary adverse drug effects⁹  and potential disruption of the gut microbiome.¹⁰  For example, many children with AOM can be treated for 5 or 7 days,⁴  and we should follow our adult medicine colleagues, who treat sinusitis and even pneumonia for 5 to 7 days, as opposed to the traditional and ubiquitous 10 days of therapy for most pediatric infections.¹¹ 

When pediatricians doubt whether a child needs an antibiotic for an ARTI, this report provides more reassurance that we can safely avoid prescribing. Most ARTIs do not need antibiotics, but all need a clearly communicated plan. When antibiotics are indicated, short and narrow spectrum should be the rule.

ARTI

acute respiratory tract infection

AOM

acute otitis media