Clonal Spread of mef -Positive Macrolide-Resistant Streptococcus pneumoniae Isolates Causing Invasive Disease in Adults in Germany

Abstract

Isolates (3,845) obtained from German adults with invasive pneumococcal disease between 1992 and 2004 were investigated. Of these, 430 isolates (11.2%) were erythromycin A nonsusceptible. Macrolide resistance genotypes and multilocus sequence types were determined. Among the isolates, 35.6% were erm(B) positive and 63.5% were mef positive. Over the study period, the frequency of resistance rose significantly from 2.2 to 17.0% (P < 0.001). A serotype 14, sequence type 9 clone was the most widespread.Streptococcus pneumoniae continues to be a significant cause of morbidity and mortality in humans. The worldwide increase in antibiotic resistance in pneumococci has become a serious infectious-disease problem within the last 20 years. Macrolide resistance in S. pneumoniae is usually caused by the presence of the erm(B) or the mef(E) or mef(A) resistance determinant. The erm(B) gene encodes a 23S rRNA methylase that confers resistance to 14-, 15-, and 16-member-ring macrolides, lincosamides, and streptogramin B. The mef(E) and mef(A) genes, which are carried by different genetic elements, encode an efflux pump that leads to resistance to 14-and 15-member-ring macrolides (the M phenotype) (14,20). Other rare mechanisms of macrolide resistance are changes in a highly conserved region of domain V of 23S rRNA, which plays a key role in macrolide binding, and in ribosomal proteins L4 and L22 (3, 5, 18, 21).Multilocus sequence typing (MLST) is a recently developed technique that produces unambiguous molecular typing data by using the sequences of seven loci to obtain an allelic profile of each strain (6, 11; http://www.mlst.net). The present study used this technique to analyze the genetic relatedness of clinical erythromycin A-resistant strains of S. pneumoniae isolated from adults with invasive pneumococcal disease in Germany.The German National Reference Center for Streptococci received consecutive isolates from 126 clinical microbiological laboratories throughout Germany. Inclusion criteria were isolation from an individual of Ͼ16 years and isolation from a normally sterile body site.MIC testing, serotyping, the determination of resistance genotypes and phenotypes, and MLST of 62 randomly selected macrolide-resistant strains were performed as described previously (11, 13).Multilocus sequence types were analyzed using the program eBURST, which displays relationships between closely related isolates of a bacterial species or population. eBURST, unlike cluster diagrams, trees, or dendrograms, uses a simple but appropriate model of bacterial evolution in which an ancestral (or founding) genotype increases in frequency in the population and, while doing so, begins to diversify to produce a cluster of closely related genotypes that are all descended from the founding genotype. This cluster of related genotypes is referred to as a clonal complex (8; http://eburst.mlst.net). A phylogenetic tree using maximum likelihood was created with the program Puzzle (19; http://genius.dkfz-heidelberg.de).A total of 3,845 isolates were con...

Serotypes, Clones, and Mechanisms of Resistance of Erythromycin-Resistant Streptococcus pneumoniae Isolates Collected in Spain

“…The MLS B phenotype is prevalent in the majority of European countries, whereas the M phenotype predominates in North America (13,32) and some European countries (England and Germany) (1,33 (38).…”

Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus pneumoniae over a 30-year period

“…The prevalence of macrolide resistance mechanisms differs considerably among countries, as shown in Table 2 [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]. The emergence of pneumococci that carry both ermB and mefE macrolide resistance genes is a cause for concern, especially in Asian countries, Russia, South Africa, and the USA [52,59].…”

“…Spain 9V -ST156 (serotypes 9V and 14) has been an important cause of IPD in many countries, before and after PCV7 introduction, and usually shows resistance to penicillin and co-trimoxazole [15,78,79]. The prevalence of England 14 -ST9, associated with the spread of macrolide resistance (mefA) in the 1990s in the USA, Canada, the UK, Germany, Norway, Greece, and Italy, decreased significantly after the introduction of PCV7 [44,48,80,81]. The high rate of penicillin and macrolide resistance detected in Asia and the USA was partially related to the spread of Taiwan 19F -ST236 [55,82].…”

Polyclonal Population Structure of Streptococcus pneumoniae Isolates in Spain Carrying mef and mef plus erm (B)

“…Despite the interest in this association on the evolution of macrolide and ketolide resistance, very few studies have investigated the population biology of a collection of isolates recovered during different time periods and/or from different geographic origins (13,26). In Spain, population structure studies have shown that resistance in S. pneumoniae international clones, such as clones Spain 9V -3 and England 14 -9, are mainly associated with those endowed with the M phenotype (1, 2), whereas clones Spain 23F -1 and Spain 6B -2 are associated with isolates endowed with the MLS B phenotype (14).…”