The antibacterial susceptibilities of 6,646 Streptococcus pneumoniae isolates collected in 38 countries from patients >or=65 years of age with community-acquired respiratory tract infections (RTIs) during years 1-5 of the PROTEKT study (1999-2004) were analysed. Rates of erythromycin resistance (36.0%), penicillin non-susceptibility (31.3%; 20.2% resistant plus 11.1% intermediately susceptible) and resistance to multiple antibacterials (37.2%) were stable over the 5 years. The most common macrolide resistance mechanism was erm(B) (61.4%); erm(B)+mef(A) strains increased from 5.4% (year 1) to 7.4% (year 5) (P=0.037). Overall, 37.2% of isolates exhibited resistance to two or more antibacterials, including 15.9% resistant to both penicillin and erythromycin. Antibacterial resistance was highest in the Far East. Telithromycin resistance was rare (0.12%). Appropriate alternative empirical first-line therapies may be required for treating community-acquired RTIs in the elderly.