Tobacco smoking history and antibiotic-resistant infection: a systematic review and meta-analysis

Antibiotic resistance is a major global health threat, but host-level and behavioral contributors to resistant infection remain insufficiently quantified. Tobacco smoking impairs respiratory and systemic host defense and is a plausible, modifiable risk factor for resistant infection. We aimed to quantify the association between tobacco smoking history and antibiotic-resistant infection.

We conducted a systematic review and meta-analysis of observational studies. Embase, PubMed, Scopus, and Web of Science were searched from database inception through 20 April 2026. Eligible studies reported a quantitative association between tobacco smoking history, defined as current or ever smoking compared with never smoking, and antibiotic-resistant bacterial infection. Adjusted odds ratios (ORs) were prioritized, with crude ORs used where adjusted estimates were unavailable or unusable. Risk of bias was assessed using ROBINS-E. Log ORs were pooled using a random-effects model with restricted maximum likelihood estimation. Prespecified subgroup analyses were conducted according to smoking definition, resistance group, and study design. Sensitivity analyses were restricted to adjusted estimates and excluded potentially influential estimates. Small-study effects were assessed using funnel plots and Egger's test.

Forty-three studies, comprising more than 35,000 participants and contributing 43 estimates, were included. Most studies examined tuberculosis (TB)-related drug resistance (39/43, 91%); 23 studies used an ever-smoking definition, and 20 used a current-smoking definition. Tobacco smoking history was associated with higher odds of antibiotic-resistant infection (pooled OR = 1.66, 95% confidence interval [CI]: 1.33-2.07; I² = 88.4%). Associations were observed for both current smoking (OR = 1.90, 95% CI: 1.26-2.87) and ever smoking (OR = 1.48, 95% CI: 1.15-1.90), as well as for both tuberculosis-related resistance (OR = 1.58, 95% CI: 1.26-1.98) and non-tuberculosis-related resistance (OR = 3.02, 95% CI: 1.23-7.41). The associations were directionally consistent across study designs; however, the cohort estimate was imprecise and did not reach statistical significance (case-control OR = 1.60, 95% CI: 1.01-2.55; cohort OR = 1.62, 95% CI: 0.64-4.09; cross-sectional OR = 1.64, 95% CI: 1.26-2.14). The overall association remained present in the analysis restricted to adjusted estimates (OR = 1.99, 95% CI: 1.56-2.56) and after excluding three influential studies (OR = 1.70, 95% CI: 1.37-2.12). Egger's test did not indicate evidence of small-study effects (p = 0.55).

Tobacco smoking history is associated with increased odds of antibiotic-resistant infection, with the evidence predominantly derived from studies of drug-resistant tuberculosis. Smoking cessation and tobacco-control interventions may be relevant to antimicrobial-resistance containment efforts, particularly in tuberculosis programs. Evidence concerning non-tuberculosis pathogens remains sparse, and substantial heterogeneity and residual confounding limit causal interpretation.

PROSPERO Identifier CRD42024619290.