- Background. Nonresponsive acute otitis media (NR-AOM) is reported in > 10% of children with AOM treated with antibiotics. Drug-resistant Streptococcus pneumoniae is currently considered the leading cause of antibiotic failures in AOM. Nasopharyngeal colonization with S. pneumoniae was found to increase significantly during episodes of AOM. Objectives. To investigate the nasopharyngeal colonization with S. pneumoniae during NR-AOM and compare it with that found in AOM not recently treated with antibiotics (NT-AOM); to assess the predictive value of nasopharyngeal pneumococcal cultures results for the bacteriologic assessment of NR-AOM. Materials and methods. Patients age 3 to 48 months with NT-AOM and NR-AOM were prospectively studied. Simultaneous nasopharyngeal cultures for S. pneumoniae and middle ear fluid cultures were obtained at enrollment. Antibiotic susceptibility testing was performed in all S. pneumoniae isolates. Penicillin and ceftriaxone MICs for S. pneumoniae were determined by E-test. The sensitivity, specificity and positive and negative predictive values of positive or negative nasopharyngeal cultures for the presence of S. pneumoniae in middle ear fluid were calculated. Results. We studied 362 and 217 children with NT-AOM and NR-AOM, respectively. Of the children with NT-AOM and NR-AOM, 95 and 97%, respectively, were younger than 2 years of age. S. pneumoniae was isolated in the nasopharynx of 66 and 58% of children with NT-AOM and NR-AOM, respectively. Penicillin-nonsusceptible S. pneumoniae was isolated more frequently from the nasopharynx of patients with NR-AOM than from those with NT-AOM (84% vs. 47%; P < 0.01). Antibiotic susceptibility patterns were similar for S. pneumoniae isolates recovered from the nasopharynx and those from the middle ear fluid in both NT-AOM and NR-AOM. A positive nasopharyngeal culture had only little predictive value for the presence of S. pneumoniae in middle ear fluid (41 and 51% for NT-AOM and NR-AOM, respectively). However, the negative predictive value of nasopharyngeal cultures for recovery of S. pneumoniae in NR-AOM was high and significantly higher in NR-AOM than in NT-AOM (91% vs. 78%, respectively; P = 0.009). The negative predictive value of nasopharyngeal cultures for recovery of antibiotic-resistant S. pneumoniae was 95 and 93% in NT-AOM and NR-AOM, respectively. Conclusions. A significantly higher nasopharyngeal colonization rate with antibiotic-resistant S. pneumoniae was found in patients with NR-AOM than in those with NT-AOM. Negative nasopharyngeal culture for antibiotic-resistant S. pneumoniae practically rules out its presence in middle ear fluid.