Inappropriate outpatient antibiotics linked to adverse drug events, excess health care costs

Inappropriate outpatient antibiotic prescriptions in adult patients were associated with increased risk of adverse drug events and substantial health care costs, a recent study found.

Researchers used a commercial insurance database to assess a cohort of U.S. adults ages 18 to 64 years with an outpatient diagnosis of a bacterial (pharyngitis, sinusitis) or viral (influenza, viral upper respiratory infection, non-suppurative otitis media, bronchitis) respiratory infection from April 1, 2016, to Sept. 30, 2018. The exposure was receipt of an inappropriate versus appropriate oral antibiotic (i.e., non-guideline-recommended vs. guideline-recommended for bacterial infections and any vs. no antibiotic for viral infections); patients treated for pharyngitis or sinusitis with first-line antibiotics were included in the “appropriate” group. The researchers used propensity-score weighting to estimate the association between inappropriate antibiotics and adverse drug events (e.g., allergic reactions, microbiome disruption-related conditions) and used two-part models to calculate 30-day all-cause attributable health care expenditures by infection type. Results were published Nov. 9 by Clinical Infectious Diseases.

Of nearly 3.3 million eligible adults (median age, 43 years; 41% male), 43% and 56% received inappropriate antibiotics for sinusitis and pharyngitis, respectively. For viral infections, 7%, 32%, 52%, and 66% received inappropriate antibiotics for influenza, viral upper respiratory infection, nonsuppurative otitis media, and bronchitis, respectively. Among adults with bacterial infections, inappropriate antibiotics were associated with higher risk of nausea/vomiting/abdominal pain (hazard ratios [HRs], 1.10 [95% CI, 1.03 to 1.18] for pharyngitis and 1.07 [95% CI, 1.02 to 1.13] for sinusitis). Inappropriate antibiotics were also associated with increased risk for Clostridioides difficile infection (HR, 2.90; 95% CI, 1.31 to 6.41) and non-C. difficile diarrhea (HR, 1.31; 95% CI, 1.20 to 1.43) in those with pharyngitis but decreased risk in those with sinusitis (HRs, 0.49 [95% CI, 0.32 to 0.74] and 0.87 [95% CI, 0.82 to 0.93], respectively).

Among adults with viral infections, inappropriate antibiotics were associated with higher risk of non-C. difficile diarrhea in those with bronchitis (HR, 1.18; 95% CI, 1.03 to 1.35), vulvovaginal candidiasis/vaginitis in those with viral upper respiratory infection and nonsuppurative otitis media (HRs, 1.24 [95% CI, 1.14 to 1.34] and 1.39 [95% CI, 1.09 to 1.77], respectively), and unspecified allergy in those with viral upper respiratory infection, nonsuppurative otitis media, and bronchitis (HRs, 1.66 [95% CI, 1.33 to 2.08], 3.60 [95% CI, 1.81 to 7.16], and 1.59 [95% CI, 1.12 to 2.28], respectively). Mean 30-day total attributable health care expenditures were higher among adults who received inappropriate antibiotics for bacterial infections ($18 to $67) and were variable for viral infections (−$53 to $49). The highest estimated annual attributable expenditures associated with inappropriate antibiotic prescriptions were $49.6 million, $19.1 million, and $2.7 million for pharyngitis, sinusitis, and viral upper respiratory infection, respectively.

The primary limitation of the study was possible residual confounding, the authors noted. They added that eligibility for each infection-related cohort may have been subject to misclassification due to misdiagnosis or miscoding, among other limitations.

“These results support the need for increased outpatient antibiotic stewardship efforts to discourage antibiotic prescribing for viral infections, encourage appropriate selection of guideline-recommended antibiotics for bacterial infections, and reduce antibiotic-related harms and expenditures,” the authors wrote.