Serotype and genotype replacement among macrolide-resistant invasive Pneumococci in adults: mechanisms of resistance and association with different transposons

Abstract

The aim of this study was to analyze trends in adult invasive pneumococcal disease (IPD) due to macrolide-resistant strains and to study the evolution of serotypes, genotypes, and macrolide-resistant determinants of strains collected in a prospective study between 1999 and 2007 in Barcelona, Spain. IPD due to macrolide-resistant strains of serotypes included in the 7-valent conjugate vaccine (PCV7) decreased from 2.16/100,000 (pre-PCV7 period, 1999 to 2001) to 0.80/100,000 (late-PCV7 period, 2005 to 2007) (P = 0.001), whereas IPD due to macrolide-resistant strains of non-PCV7 serotypes increased from 1.08/100,000 to 2.83/100,000 (P < 0.001). These changes were related to a fall of clones of PCV7 serotypes (ST81 [P < 0.05], ST90, ST315, and ST17) and an increase in new clones of serotypes 19A and 24F (ST230) and 33F (ST717) in the late-PCV7 period. The most common phenotype was MLS(B) (90.9%), related to the erm(B) gene. The frequent association between MLS(B) phenotype and tetracycline resistance [tet(M) gene], was related to transposons of the Tn916-family such as Tn6002 or Tn3872. In conclusion, overall adult IPD rates due to macrolide-resistant pneumococci stabilized between 1999 and 2007 in Barcelona. The decrease in macrolide-resistant PCV7 pneumococci was balanced by the increase in macrolide-resistant non-PCV7 pneumococci.

FIG. 1.

Distribution of serotypes of macrolide resistant invasive S. pneumoniae strains isolated from adult patients (1999 to 2007). Lettered brackets: a, significant decrease in MR IPD due to serotype 6B in early-PCV7 compared to late-PCV7 periods; b, significant decrease in MR IPD due to serotype 6B in pre-PCV7 compared to late-PCV7 periods; c, significant increase in MR IPD due to serotype 24F in pre-PCV7 compared to late-PCV7 periods.

FIG. 2.

Distribution of major clones of macrolide resistant invasive S. pneumoniae strains isolated from adult patients (1999 to 2007). Lettered brackets: a, significant decrease of CC81 in pre-PCV7 compared to late-PCV7 periods; b, significant increase of CC230 in pre-PCV7 compared to late-PCV7 periods; c, significant increase of ST717 in pre-PCV7 compared to late-PCV7 periods.