OBJECTIVES: The incidence of community-acquired pneumonia (CAP) caused by drug resistance has increased dramatically in recent years. The aim of this analysis was to analyse the impact of antimicrobial resistance on the cost-effectiveness of different antibiotic classes (beta-lactams, macrolides, fluoroquinolones) in patients with CAP in Germany. METHODS: A decision analytic model was developed for mild-to-moderate CAP outpatient treatment. Treatment algorithms incorporated follow-up after treatment failure due to resistance or other reasons. First-line treatment included moxifloxacin (MXF), beta-lactams (AMX), or macrolides (ROX); second-line treatment used a different antimicrobial class. In contrast to existing cost-effectiveness models in CAP class-specific resistance profiles were included in the model. This allows for the analysis of the impact of antimicrobial resistance on the cost-effectiveness in addition to standard outcomes like clinical failure, hospitalisation rates and total costs. Input data were derived from surveillance studies, from literature and expert opinion. Total costs were estimated using standard sources and a third-party payer perspective in Germany. RESULTS: Total cost were €240.60 (MXF), €250.59 (ROX), and €268.91 (AMX). First-line clinical failure, second-line treatment, and hospitalisation rates were lower for MXF as compared to the other treatment options. First-line MXF treatment dominated all other treatments. Antimicrobial resistance accounted for 53% (AMX), 72% (ROX) and 2% (MXF) of all clinical failures and 37% (AMX), 56%(ROX) and 1% (MXF) of all hospitalisations. CONCLUSION: Antimicrobial resistance has a significant impact on the cost-effectiveness of empirical treatment of CAP. The first-line use of moxifloxacin in CAP is a dominant strategy even in a country with a low level of resistance like Germany.