Is delayed antibiotic prescribing harmful to patients with respiratory tract infections?

Delayed prescription of antibiotics appears safe and effective for most patients with respiratory tract infectoins, even those at higher risk, according to an individual patient data meta-analysis. Delayed prescribing also results in similar symptom duration as no antibiotic prescribing and is not likely to lead to higher complication rates or to decrease patient satisfaction than immediate prescribing.

“Delayed prescribing could be used as a standalone interventional approach, but it might also be a way of resolving mismatched expectations between clinician and patient,” the researchers said.

The databases of Cochrane Central Register of Controlled Trials, Ovid Medline, Ovid Embase, EBSCO Cinahl Plus, and Web of Science were searched to identify randomized controlled trials (RCTs) and observational cohort studies that compared delayed prescribing with no antibiotic and immediate prescribing among patients with respiratory tract infections in the community.

Nine RCTs and four observational studies including a total of 55,682 patients were eligible for the meta-analysis. Delayed antibiotic prescribing demonstrated no significant difference in follow-up symptom severity (seven-point scale) compared with either immediate prescribing (adjusted mean difference [AMD], –0.003, 95 percent confidence interval [CI], –0.12 to 0.11) or no antibiotics (AMD, 0.02, 95 percent CI, –0.11 to 0.15). [BMJ 2021;373:n808]

On the other hand, patients who received delayed prescription had slightly longer symptom duration than those given immediate antibiotics (11.4 vs 10.9 days) but showed similar duration relative to no antibiotics. Complications resulting in hospitalization or death were lower with delayed prescribing compared with no antibiotics (odds ratio [OR], 0.62, 95 percent CI, 0.30–1.27) and immediate prescribing (OR, 0.78, 95 percent CI, 0.53–1.13).

Furthermore, reconsultation rates significantly decreased (OR, 0.72, 95 percent CI, 0.60–0.87) and patient satisfaction increased (AMD, 0.09, 95 percent CI, 0.06­–0.11) with delayed vs no antibiotics. Of note, previous duration of illness, fever, comorbidity, or symptoms severity did not modify the effect of delayed prescribing compared with immediate and no antibiotics.

“The reasons for reduced reconsultation rates are unclear, but one suggestion is that if a prescription is delayed, by the time the antibiotic course has finished, symptoms will have had more time to settle and so reconsultation is less likely; or it could be that secondary opportunistic bacterial infections that start later after an initial viral illness are more effectively managed by the later start of a delayed prescription,” the researchers said.

Findings from the large GRACE trial supported the second suggestion: one of the groups that reported beneficial effects with antibiotics were those for whom evidence was found of coinfection with viruses and bacterial pathogens. [Clin Microbiol Infect 2018;24:871-876]

Children aged <5 years given delayed antibiotics, however, had a slightly higher follow-up symptoms severity than those who received immediate antibiotics (AMD, 0.10, 95 percent CI, 0.03–0.18), but no increased severity was observed in the older age group.

“This finding suggests that while the effect might be statistically significant, these differences are not clinically significant, and our patient and public involvement panel did not feel that they were likely to be meaningful to patients,” the researchers noted.