- Background: Streptococcus pneumoniae is a common cause of community-acquired alveolar pneumonia (CAAP) and acute otitis media (AOM) in children. Romania has high rates of S. pneumoniae antibiotic resistance. The pneumococcal conjugated vaccines (PCVs) are not being used routinely in this country. The aims of the study were as follows: 1) to compare pneumococcal antibiotic resistance patterns in AOM and CAAP in children from central Romania and 2) to compare differences in the distribution of pneumococcal serotypes isolated from the middle ear fluid (MEF) of children with AOM and from the nasopharynx (NP) of children with CAAP. Methods: Children younger than 5 years old with AOM or with radiologically confirmed CAAP were prospectively enrolled. Samples from MEF and NP were evaluated for antibiotic susceptibility and serotyping. Results: Eighty-eight children with CAAP and 68 with AOM were enrolled. Of the MEF and CAAP isolates, 64 (94.1%) and 79 (89.7%) were penicillin nonsusceptible, respectively. The pneumococcal serotypes distribution in AOM was similar to those in CAAP except for serotype 19F, which was more common in AOM. Overall, 89.7% and 85.8% of all serotypes in AOM and CAAP patients, respectively, were covered by 13-valent PCV. Conclusions: MEF and NP-CAAP S. pneumoniae isolates were similar in regard to serotype distribution and antibiotic resistance. S. pneumoniae antibiotic resistance rates were extremely high. Thirteen-valent PCV has the potential to reduce both the burden of disease as well as the rates of antibiotic-resistant S. pneumoniae in both diseases.