- Background. Penicillin-nonsusceptible Streptococcus pneumoniae isolates are confined mainly to a few sero-groups. Capsular transformation may serve as a mechanism for spreading antibiotic resistance to new serotypes. Methods. Antibiogram and molecular typing, by pulsed-field gel electrophoresis (PFGE), were performed on 46 nasopharyngeal and middle ear fluid (MEF) isolates expressing serotype 11A, 45 MEF isolates expressing serotype 15B/C (recovered during 1998-2003 from Israeli children <5 years old), and 57 MEF isolates expressing serotype 19F (recovered during 1998-2001 from Costa Rican children <7.5 years old). Results. PFGE patterns showed that 49 (86%) of 57 serotype 19F isolates and 19 (41%) of 46 serotype 15B/ C isolates were closely related. The vast majority of these isolates (80% of serotype 19F and 100% of serotype 15B/C isolates) were nonsusceptible to penicillin. Multilocus sequence typing (MLST) data show that the serotype 15B/C isolates belonged to the ST346 cluster, whereas the serotype 19F isolates were a single-locus variant of ST346. For serotype 11A isolates, PFGE patterns and MLST analysis showed that 8 (80%) of the 10 penicillin-nonsusceptible isolates belonged to a single clone-namely, ST156-which was identical to the international Spain 9V -3 clone. Conclusions. Penicillin-nonsusceptible pneumococcal clones of serotypes not related to those included in the 11-valent conjugate vaccines may derive from capsular transformation of vaccine-related serotypes. Of particular concern was the detection of serotype 11A variants of the successful international Spain 9V -3 clone. This phenomenon, although seemingly rare at present, can have implications for the long-term effectiveness of the conjugate vaccines.