- During the last 20 years, a dramatic increase in antibiotic resistance among pneumococci has been observed and linked to increasing antibiotic consumption [1-4]. Several studies have suggested that reduction in antibiotic consumption leads to a reduction in the antibiotic resistance of Streptococcus pneumoniae in the community [2, 5-7]. However, other studies could not demonstrate such an effect [8-10]. The relationship between antibiotic consumption and resistance is complex. Some antimicrobial agents select resistant pneumococcal strains more effectively than others [8, 11-15]. Moreover, the rate of the decrease in resistance expected after a decrease in antibiotic use depends on both the fitness cost of resistance for the bacteria and the extent of the reduction in consumption [16, 17]. If fitness cost is minimal or if the reduction in antibiotic use is small, antibiotic resistance may continue increasing, albeit perhaps more slowly, or it may decline gradually. However, if resistance exacts a strong fitness cost (with respect to transmissibility) on the bacteria, then a quick and significant decrease in resistance would be expected after a major decrease in antibiotic consumption . A recent study in rats suggested that penicillin resistance in S. pneumoniae, particularly high-level resistance, carries a substantial fitness cost . Another recent study showed a fitness cost of fluoroquinolone-resistant mutants of S. pneumoniae . A complicating factor is the presence of dual and multiple resistance, because reduction mainly in the use of a single antibiotic may not result in the expected reduction in resistance, because of coselection of resistance caused by the continued use of other antibiotics . Surveillance of antibiotic prescriptions in children <5 years old has been ongoing in southern Israel since 1998. We observed yearly higher antibiotic prescription rates during the cold months (October through March) than during the warm months (April through September). We hypothesized that macrolide and β-lactam resistance in S. pneumoniae carries a substantial fitness cost, as suggested in experimental models. This would be observable as a yearly decline in the proportion of resistant isolates during the warm months, when antimicrobial prescribing is reduced. Therefore, our objectives were to (1) determine the seasonal prescription patterns of commonly used oral antibiotics in young children and (2) compare the seasonal antibiotic prescribing patterns with the seasonal resistance patterns of pneumococci isolated from middle ear fluid (MEF) during acute otitis media (AOM).