Streptococcus pneumoniae serogroup 19 clonal complex 320/271 (CC320/271) includes important multidrug-resistant (MDR) clones, including sequence type 271(ST271), responsible for both invasive pneumococcal disease (IPD) and noninvasive pneumococcal disease in most Asian countries (1, 2) and in parts of China (3). In the United States and other western countries, serotype 19A-ST320, a multidrug-resistant (MDR) clone, has been highly successful after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) (4). ST320 is a double-locus variant (DLV) of the originally described Taiwan 19F -14 (Pneumococcal Molecular Epidemiology Network; PMEN14) clone, ST236, from isolates from a Taiwanese hospital in 1997 (5) and has undergone a capsular switch to nonvaccine serotype 19A, likely through recombination that altered the wzy polymerase gene. In mainland China, 43.8% of cases of IPD were reportedly due to serogroup 19 during 2005 to 2011, with 84.7% of isolates belonging to CC320/ 271, including ST271, ST320, and ST236 (3). In Hong Kong, we reported the introduction of the Taiwan 19F -14 (ST236) clone back in 1999 (6), prior to the introduction of PCV7. These strains were resistant to -lactams, tetracyclines, and macrolides but susceptible to chloramphenicol and replaced the predominant MDR Spain 23F -1 and Spain 6B -2 clones in the late 1990s (7). The Hong Kong Special Administrative Region (HKSAR) introduced PCV7 to the childhood immunization program in October 2009 and subsequently introduced the 10-valent vaccine in October 2010 and PCV13 in 2011 in keeping with the changes in the vaccine coverage of prevalent serotypes. Of the serotypes included in PCV7, serotype 19F is the least likely to evoke a protective immune response according to both vaccine efficacy trials and in vivo studies (8, 9). Therefore, despite the initial decrease in carriage and invasive disease due to serotype 19F, reemergence of the disease might be anticipated due to a weaning of antibody responses over time. This is reflected by recent studies in Hong Kong comparing pre-and postvaccination serotype carriage, where a significant difference was not found for serotype 19F (10). In addition, during this period, an increasing level of resistance of S. pneumoniae to the third-generation cephalosporin cefotaxime was observed. Given the ability of pneumococci to adapt and transform, we sought to examine the levels of antimicrobial and -lactam resistance of these isolates and study the polymorphisms of amino acid sequences of penicillin binding protein 1a (PBP1a), PBP2b, and PBP2x that might be related to different levels of