Background.A 3-day intramuscular ceftriaxone regimen was superior to a 1-day regimen in the treatment of nonresponsive acute otitis media caused by resistantStreptococcus pneumoniae. However, the effect of various regimens of intramuscular cefriaxone on the nasopharyngeal carriage ofS. pneumoniaeand especially that of resistant strains during and after therapy has not been thoughtfully studied.Objectives.To compare the effect of one dose and three dose intramuscular ceftriaxone regimens on the nasopharyngeal carriage ofS. pneumoniaein patients with nonresponsive acute otitis media treated with these two regimens and to document the dynamics of nasopharyngeal colonization withS. pneumoniaeduring and after completion of these two therapeutic regimens.Patients and methods.In a prospective study performed during January, 1998, through September, 1999, 170 evaluable patients ages 3 to 36 months with nonresponsive acute otitis media were randomized to receive the 1 (n= 83)- or 3 (n= 87)-day intramuscular ceftriaxone regimen (50 mg/kg/day), respectively. Nasopharyngeal cultures forS. pneumoniaewere obtained on Days 1, 4 to 5, 11 to 14 and 28 to 30. Susceptibility ofS. pneumoniaeto penicillin and ceftriaxone was determined by E-test.Results.On Day 1 nasopharyngealS. pneumoniaecarriage was found in 108 (64%) patients, 54 in each treatment group. Forty-seven of 54 (87%) and 9 of 54 (17%)S. pneumoniaeisolates from the one dose group were nonsusceptible to penicillin and ceftriaxone, respectively; the respective values in the three dose group were 49 of 54 (91%) and 8 of 54 (15%). On Days 4 and 5 negative nasopharyngeal cultures were achieved in 43 of 83 (52%) and 70 of 87 (80%) cases from the one dose and three dose group, respectively (P< 0.001). Eradication of penicillin-nonsusceptibleS. pneumoniaewas achieved on Day 4 to 5 in 18 of 49 (37%) and 39 of 49 (80%) organisms isolated from the one dose and three dose groups, respectively (P< 0.001). NasopharyngealS. pneumoniaecarriage among evaluable patients on Days 11 to 14 and Days 28 to 30 was 43 of 69 (62%) and 31 of 45 (69%) for the one dose group and 42 of 73 (58%) and 31 of 50 (62%) for the three dose group, respectively (Pnot significant). A decrease was observed during the study period in the proportion of highly penicillin-resistantS. pneumoniaeisolated in the three dose group compared with the one dose group (30, 24, 17 and 13%vs.30, 27, 19 and 26% at Days 1, 4 to 5, 11 to 14 and 28 to 30, respectively;P= 0.05).Conclusions.A marked reduction in the carriage of penicillin-nonsusceptibleS. pneumoniae(including highly penicillin-resistant organisms) was achieved on Days 4 to 5 of therapy with both ceftriaxone regimens. The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day regimen in the reduction of carriage during the treatment period. The reduction of overallS. pneumoniaenasopharyngeal carriage by both ceftriaxone regimens was a short-lived phenomenon followed by rapid recolonization of the nasopharynx.