Findings Call for Caution: Broad-Spectrum Antibiotics Raise ADE Risks in Outpatient Pneumonia Patients

Findings indicate that broad-spectrum antibiotics, while effective against a wide range of pathogens, were linked to a higher incidence of adverse drug events (ADEs) in patients treated for CAP. Based on the findings, the researchers emphasize the importance of antimicrobial stewardship to encourage the careful use of broad-spectrum antibiotics, aiming to reduce antibiotic-related ADEs.

Community-acquired pneumonia is a common infection often managed in outpatient settings and typically affects otherwise healthy individuals. Current evidence on the comparative safety of antibiotic regimens for treating CAP remains limited, especially amid growing concerns about antibiotic resistance and the varying safety profiles of different treatments. To fill this knowledge gap, Anne M Butler, Washington University School of Medicine, St. Louis, MO, USA, and colleagues assessed the risk of adverse drug events linked to antibiotic regimens used for treating community-acquired pneumonia in otherwise healthy, non-elderly adults.

For this purpose, the researchers conducted an active comparator new-user cohort study from 2007 to 2019, focusing on commercially insured adults aged 18 to 64 diagnosed with outpatient CAP confirmed by chest X-ray and prescribed a same-day CAP-related oral antibiotic regimen. The follow-up duration for ADEs varied from 2 to 90 days, with specific conditions such as renal failure monitored over 14 days. They estimated risk differences per 100 treatment episodes and risk ratios using propensity score-weighted Kaplan-Meier functions and also included ankle/knee sprains and influenza vaccination as negative control outcomes.

Key Findings of the Study

• Among 145,137 otherwise healthy patients with community-acquired pneumonia and no comorbidities:
  • 52% received narrow-spectrum regimens:
  • 44% were prescribed macrolides
  • 8% received doxycycline
  • 48% received broad-spectrum regimens:
  • 39% were prescribed fluoroquinolones
  • 7% received β-lactams
  • 3% received a combination of β-lactam and macrolide
  • Compared to macrolide monotherapy, broad-spectrum antibiotic regimens were associated with an increased risk of several adverse drug events:
  • β-lactam regimen:
  • Nausea/vomiting/abdominal pain: Risk difference (RD) per 100 = 0.32
  • Non-Clostridioides difficile diarrhea: RD per 100 = 0.46
  • Vulvovaginal candidiasis/vaginitis: RD per 100 = 0.36
  • Narrow-spectrum antibiotic regimens largely exhibited similar risk profiles for ADEs.
  • The negative control outcome analysis showed similar risks, indicating minimal confounding.

The authors state that the study's results contribute to growing evidence indicating that transitioning prescribing practices from broad-spectrum to narrower-spectrum antibiotics could help prevent adverse drug events (ADEs).

They noted, "Ultimately, understanding antibiotic-related harms can empower patients, prescribers, and stewardship programs to make informed decisions regarding antibiotic use."

Reference:

Butler, A. M., Nickel, K. B., Olsen, M. A., Sahrmann, J. M., Colvin, R., Neuner, E., A, C., Fraser, V. J., Durkin, M. J., & Epicenters Program, C. P. Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciae519