- Background: The objective of the study was to evaluate whether the increase in antibiotic-resistant Streptococcus pneumoniae carriage was associated with antibiotic use in the community in children in Southern Israel. Methods: All the prescriptions given to Bedouin children <5 years old enlisted in 2 sentinel primary pediatric clinics treating ∼20% of the Bedouin pediatric population of this age range were recorded, from 1998 to 2005. Nasopharyngeal pneumococcal isolates obtained during the same period from healthy children <5 years old were collected and antibiotic susceptibility was determined. Results: A total of 1488 of 1927 (77.7%) cultures were positive for S. pneumoniae. The proportion of S. pneumoniae with penicillin minimal inhibitory concentration ≥1.0 μg/mL increased from 8% to 21% (P < 0.01); resistance to clindamycin from 9% to 22%; resistance to erythromycin from 13% to 30%; resistance to tetracycline from 13% to 31%; and multidrug resistance from 16% to 30%. The total annual antibiotic prescription rates decreased by 19%, from 3867 to 3191 prescriptions per 1000 children (P < 0.001). This was mainly the result of a reduction in amoxicillin ± clavulanate prescriptions (from 3046 to 2582; P < 0.001). Oral cephalosporin, erythromycin and penicillin prescription rates decreased significantly as well (P < 0.001) whereas azithromycin prescription rates increased significantly (P < 0.001). Conclusions: We suggest that the increased carriage of S. pneumoniae resistant to multiple antibiotics is possibly associated to the increased azithromycin consumption. Reduction of total antibiotic use may not be sufficient as long as antibiotics with high potential to promote multidrug resistance, given their pharmacokinetics and pharmacodynamics characteristics, are widely used.