Susceptibility testing results for Streptococcus pneumoniae isolates (n ‫؍‬ 2,279) from eight European countries, examined in the PneumoWorld Study from 2001 to 2003, are presented. Overall, 24.6% of S. pneumoniae isolates were nonsusceptible to penicillin G and 28.0% were resistant to macrolides. The prevalence of resistance varied widely between European countries, with the highest rates of penicillin G and macrolide resistance reported from Spain and France. Serotype 14 was the leading serotype among penicillin G-and macrolide-resistant S. pneumoniae isolates. One strain (PW 158) showed a combination of an efflux type of resistance with a 23S rRNA mutation (A2061G, pneumococcal numbering; A2059G, Escherichia coli numbering). Six strains which showed negative results for mef(A) and erm(B) in repeated PCR assays had mutations in 23S rRNA or alterations in the L4 ribosomal protein (two strains). Fluoroquinolone resistance rates (levofloxacin MIC > 4 g/ml) were low (Austria, 0%; Belgium, 0.7%; France, 0.9%; Germany, 0.4%; Italy, 1.3%; Portugal, 1.2%; Spain, 1.0%; and Switzerland, 0%). Analysis of quinolone resistance-determining regions showed eight strains with a Ser81 alteration in gyrA; 13 of 18 strains showed a Ser79 alteration in parC. The clonal profile, as analyzed by multilocus sequence typing (MLST), showed that the 18 fluoroquinoloneresistant strains were genetically heterogeneous. Seven of the 18 strains belonged to new sequence types not hitherto described in the MLST database. Europe-wide surveillance for monitoring of the further spread of these antibiotic-resistant S. pneumoniae clones is warranted.

Continuous nationwide surveillance of antibiotic resistance in invasive pneumococcal disease was performed in Germany between 1992 and 2000, with a total of 2586 strains being isolated. The average resistance rates to erythromycin and clindamycin were 7.7% and 3.5%, respectively, throughout the study period; 3.3% of strains were found to have intermediate resistance to penicillin. Over the study period an increase in both macrolide and penicillin resistance was observed. The percentage of strains exhibiting reduced susceptibility to penicillin increased from 1.8% in 1992 to 5.8% in 2000. A dramatic increase in resistance was observed with erythromycin, where the resistance rate rose from 3.0% in 1992 to 15.3% in 2000. Of the erythromycin-resistant strains, 86 (43.4%) and 111 (56.1%) belonged to the erm(B) and mef types of resistance, respectively. An analysis of macrolide consumption data during the study period showed that erythromycin resistance was highly correlated to the consumption of newer bd and od macrolides (r = 0.89, P < 0.01).

Human TLR1 plays an important role in host defense against Mycobacterium tuberculosis. Our aim was to analyze the association of the loss of TLR1 surface expression and TLR1 SNPs with susceptibility to TB. TLR1neg and TLR1pos cells from healthy individuals were identified by flow cytometry and compared by sequencing. TLR1 expression was measured using quantitative real-time PCR and immunoblotting. TLR1 SNP analyses of healthy individuals and TB patients from EU-C and Ghana were performed, and association of the TLR1 genotypes with increased risk of developing TB was statistically evaluated. Lack of TLR1 surface expression accompanied by impaired function was strongly associated with TLR1 SNP G743A. Genotyping of EU-C controls and TB patients revealed an association of TLR1 743A/1805G alleles [OR 2.37 (95% CI 1.13, 4.93), P=0.0219; OR 2.74 (95% CI 1.26, 6.05), P=0.0059] as well as TLR1neg 743AA/1805GG versus TLR1pos genotypes 743AG/1805TG [OR 4.98 (95% CI 1.64, 15.15), P=0.0034; OR 5.70 (95% CI 1.69, 20.35), P=0.0015] and 743AG + GG/1805TG + TT [OR 3.54 (95% CI 1.29, 9.90), P=0.0086; OR 4.17 (95% CI 1.52, 11.67), P=0.0025] with increased susceptibility to TB. No association of G743A with TB was found in Ghana as a result of a low frequency of genotype 743AA. Our data gain new insights in the role of TLR1 in M. tuberculosis defense and provide the first evidence that TLR1 variants are associated with susceptibility to TB in a low-incidence country.

In a nationwide study in Germany covering 13 clinical microbiology laboratories, a total of 307 Streptococcus pyogenes (mainly pharyngitis) and 333 Streptococcus pneumoniae (respiratory tract infections) strains were collected from outpatients less than 16 years of age. The MICs of penicillin G, amoxicillin, cefotaxime, erythromycin A, clindamycin, levofloxacin, and telithromycin were determined by the microdilution method. In S. pyogenes isolates, resistance rates were as follows: penicillin, 0%; erythromycin A, 13.7%; and levofloxacin, 0%. Telithromycin showed good activity against S. pyogenes isolates (MIC 90 ‫؍‬ 0.25 g/ml; MIC range, 0.016 to 16 g/ml). Three strains were found to be telithromycin-resistant (MIC > 4 g/ml). Erythromycin-resistant strains were characterized for the underlying resistance genotype, with 40.5% having the efflux type mef(A), 38.1% having the erm(A), and 9.5% having the erm(B) genotypes. emm typing of macrolide-resistant S. pyogenes isolates showed emm types 4 (45.2%), 77 (26.2%), and 12 (11.9%) to be predominant. In S. pneumoniae, resistance rates were as follows: penicillin intermediate, 7.5%; penicillin resistant, 0%; erythromycin A, 17.4%; and levofloxacin, 0%. Telithromycin was highly active against pneumococcal isolates (MIC 90 < 0.016 g/ml; range, 0.016 to 0.5 g/ml). The overall resistance profile of streptococcal respiratory tract isolates is still favorable, but macrolide resistance is of growing concern in Germany.Streptococcus pyogenes is responsible for the majority of cases of pharyngitis in children and adolescents and can also cause severe life-threatening diseases, such as necrotizing fasciitis and toxic shock syndrome (6). Streptococcus pneumoniae continues to be a significant cause of morbidity and mortality in humans and is responsible for respiratory tract infections and otitis media (15).Macrolide resistance in S. pneumoniae is usually caused by the presence of the erm(B) or mefE [renamed mef(A)] resistance determinants. The erm(B) protein encodes a 23S rRNA methylase, and most pneumococcal strains that harbor the gene are resistant to 14-, 15-, and 16-membered-ring macrolides, lincosamides, and streptogramin B (MLS B phenotype). The mef(A) protein encodes an efflux pump that leads to resistance to only 14-and 15-membered-ring macrolides (24). Other mechanisms of macrolide resistance have only been described in a few clinical isolates of S. pneumoniae, and changes were clustered in a highly conserved sequence of L4 and in the nucleotide residues of domain V of 23S rRNA, which have a key role in macrolide binding (5,7,26).Macrolide resistance has also been increasingly detected in S. pyogenes in Europe and other parts of the world and is mediated by erm(A), mef(A) and, less commonly, by erm(B) mechanisms.Telithromycin (HMR 3647) is the first of a novel family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections.The ketolides are a new addition to the MLS group of antimicrobials. Ketolides ar...

A population-based survey of invasive pneumococcal disease (IPD) was conducted among adults in North-Rhine Westphalia, Germany. The study included 202 of the 386 hospitals in the region, together with the 27 microbiological laboratories that submitted reports of IPD in these hospitals to the National Reference Centre for Streptococci. The reports of 16 laboratories were comprehensively reviewed. Most (95.8%) IPD isolates were susceptible to penicillin G, but 14.5% were resistant to clarithromycin. Serotypes 14 (15.6%), 3 (9.3%), 4 (7.1%) and 7F (7.9%) were the most common. The serotype coverage of the 23-valent pneumococcal polysaccharide vaccine was 80.8%. During 2001-2003, the annual incidence of IPD, after correcting for laboratory and hospital under-reporting, was 16.2/100 000 in individuals aged >or= 65 years. In three university hospitals, blood cultures were obtained for only 37% of patients with community-acquired pneumonia, and fewer than one-third of such cultures were obtained in one hospital before antibiotics were prescribed, suggesting that the true incidence of IPD was closer to 50/100 000.