Smoking history is not independently associated with broad-spectrum antibiotic use in two nationally representative cohorts of adult men in South Korea

Background: Smoking is linked to an increased risk of infectious diseases, underscoring the importance of smoking prevention and cessation in improving public health. However, using smoking history as a surrogate marker of infection severity may have unintended consequences, potentially prompting clinicians to prescribe broad-spectrum antibiotics more readily for patients with a history of smoking. This study evaluated whether smoking history was independently associated with the increased prescription of broad-spectrum antibiotics to adult men in the general population of South Korea. Methods: We analyzed data from two nationally representative cohorts of Korean adult men enrolled in the National Health Insurance Service (NHIS): the National Sample Cohort (NSC) and the Health Screening Cohort (HEALS). Smoking status was classified using data from self-reported questionnaires collected from 2009 to 2013. Participants were followed from 2013 to 2021 to assess broad-spectrum antibiotic use. The primary outcome was the receipt of at least one prescription of antipseudomonal penicillins, antipseudomonal cephalosporins, carbapenems, or glycopeptides for at least 3 consecutive days. We used a composite outcome to assess the use of antibiotics targeting resistant Gram-negative organisms. After accounting for confounders, the association between smoking status and antibiotic use was evaluated using multivariable regression models. Results: The NHIS–NSC cohort included 50,134 adult men (17,300 never-smokers and 32,834 smokers), and the NHIS–HEALS cohort included 42,979 adult men (20,145 never-smokers and 22,834 smokers). In both cohorts, the rate of prescription of broad-spectrum antibiotics was low. For the composite outcome, the adjusted incidence rate ratios (IRR) for smokers compared to never-smokers were 1.55 (95% confidence interval [CI] = 0.67–3.52) in NHIS–NSC and 0.59 (95% CI = 0.24–1.46) in NHIS–HEALS. Smoking history was not significantly associated with the use of different antibiotic subclasses in these cohorts. For glycopeptides, the adjusted IRRs were 1.07 (95% CI = 0.23–5.10) in NHIS–NSC and 3.47 (95% CI = 0.70–17.13) in NHIS–HEALS, and neither association was statistically significant. Conclusion: In these two cohorts, the prescription rates of broad-spectrum antibiotics were low, and we did not observe evidence of an independent association between smoking history and their use. These findings suggest that smoking history alone should not be regarded as sufficient justification for prescribing broad-spectrum agents and emphasize the importance of basing prescribing decisions on comprehensive clinical assessment.