Rapid spread in Norway of an erythromycin-resistant pneumococcal clone, despite low usage of macrolides.

During the last 4 years, Norway has experienced an increase in macrolide resistance among systemic isolates of Streptococcus pneumoniae. The Norwegian reference laboratory for pneumococci received the isolates from over 85% of the Norwegian cases of systemic pneumococcal disease in the period studied. To study the details of the increased macrolide resistance, all macrolide-resistant systemic pneumococcal isolates (410 isolates) collected in the period from 1995 to 2005 were characterized phenotypically, and a representative selection of 68 strains was also studied genotypically. The serogroups most frequently associated with macrolide resistance in the studied period were 14, 6, 23, 19, and 9. The resistance M-type was expressed in 85% of the resistant isolates. Of the 68 isolates analyzed by multilocus sequence typing, 19 different sequence types (STs) were represented, including several of the international resistant clones. All but one of the clones appeared at a low frequency; mainly as isolated cases. The increase in macrolide resistance seen from 2001 to 2005 proved to be caused by ST-9, defined as the England(14)-9 clone by the Pneumococcal Molecular Epidemiology Network. All ST-9 isolates tested, carried the mef(A) gene and expressed the resistance M-type. This clone first appeared in the Oslo region in 1993, but was by 2005 isolated from all over the country. Children were overrepresented among the cases caused by this clone; however, people aged 20-29, possibly involving the parent generation, were also represented at an increased frequency. The England(14)-9 clone has been able to spread successfully in the Norwegian population despite a relatively low consumption of macrolides.

Molecular characterization of non-penicillin-susceptible Streptococcus pneumoniae in Norway.

A total of 125 non-penicillin-susceptible Streptococcus pneumoniae isolates were received at the Norwegian Institute of Public Health in the period from 1995 to 2001. The strains were tested for antimicrobial susceptibility, serotyped, and genotyped by multilocus sequence typing (MLST); and their penicillin-binding proteins (PBPs) were typed by restriction fragment length polymorphism analysis of their pbp genes. Of the 125 strains, 48 (38%) were fully resistant to penicillin and 77 (62%) were intermediately resistant to penicillin. Most of the strains resistant to penicillin were also resistant to one or several additional antibiotics. The most frequent serotypes among the non-penicillin-susceptible strains were 14, 9V, 19F, 23F, and 6B. MLST analysis showed a high degree of genetic diversity among the 119 strains tested, with a total of 74 different sequence types. Six of the 26 internationally known resistant clones were present; the Spain(9V)-3 clone was the most frequent, with 19 isolates. A total of 74 (62%) of the isolates were related to 1 of the 26 international clones. Restriction enzyme analyses of the pbp1a, pbp2b, and pbp2x genes revealed 12, 12, and 19 different patterns, respectively; and a total of 43 different PBPs types were demonstrated. Our data indicate that the non-penicillin-susceptible strains in Norway are highly diverse genetically and that limited spread of the internationally known resistant strains occurred in the country in the period examined.