Molecular Epidemiology of Telithromycin-Resistant Pneumococci in Finland

In our previous study, we described 26 clinical pneumococci with heterogeneous resistance to telithromycin (TEL). In this resistance type, separate colonies grew inside the inhibition zone around the TEL disk in a disk diffusion test (8). In this study we investigated the molecular epidemiology of these 26 isolates and compared them to erm(B)-positive but TEL-susceptible (Tels) pneumococci (n = 66) (9). Published methods were used for antimicrobial susceptibility testing (7), serotyping (3), pulsed-field gel electrophoresis (PFGE) typing (5, 4), and multilocus sequence typing (MLST) (1). PFGE was performed for all TEL-resistant (Telr) isolates, for 3 zone isolates (8), and for 22 randomly selected Tels, erm(B)-positive isolates, but MLST typing and serotyping were performed only for Telr isolates. Our results were compared to international databases (www.mlst.net and www.sph.emory.edu/PMEN). The clinical characteristics, antimicrobial susceptibilities, PFGE profiles, and sequence types (STs) of the isolates are summarized in Table ​Table1.1. Penicillin nonsusceptibility (MIC of ≥0.125 μg/ml) was less frequent among erm(B)-positive Telr isolates (4/26) than among erm(B)-positive Tels isolates (50/66) (P < 0.0001, Fisher's exact test). The same applied to penicillin and tetracycline coresistance. None of the isolates was resistant to levofloxacin or linezolid. The most frequent serotype was 19A. Telr isolates were distributed among 7 distinct PFGE types, of which type A was the most frequent with 19 isolates. Tels erm(B) isolates had more heterogeneous PFGE patterns, since 12 different PFGE types were detected among 22 Tels isolates (Fig. ​(Fig.11). FIG. 1. Dendrogram and PFGE patterns of 26 Telr, erm(B)-positive pneumococci. Telr isolates are in boldface. Respective patterns of 22 erm(B)-positive but Tels isolates are also presented. Three isolates designated with the letter V are zone isolates (isolates ... TABLE 1. Summary of clinical and molecular data for 26 clinical pneumococcal isolates with heterogeneous resistance to telithromycin MLST types 193, 271, and 273, found among our isolates, are representatives of global pneumococcal clones. ST 193 belongs to the pneumococcal global clone Greece21-30, which has been found in Greece, Brazil, the United Kingdom, and Vietnam (12, 13). The clone was reported to be penicillin susceptible but otherwise multidrug resistant, which also applies to our isolates. ST 273 is a representative of the penicillin-susceptible but erythromycin-resistant PMEN clone, Greece6B-22. Apart from Greece, this clone has been detected in Iceland, Israel, Portugal, Italy, Germany, and Switzerland (6, 11). ST 133 has been detected in Spain (www.mlst.net). ST 271 is a single-locus variant of a multidrug-resistant Taiwanese 19F clone, ST 236 (10). In one international study, ST 271 was detected worldwide and more than 85% of pneumococcal isolates with a double resistance mechanism, erm(B) and mef(E), belonged to this clonal complex (2). Our ST 271 isolate also had a double resistance mechanism. The other isolate in this study with a double mechanism had a novel ST, ST 2248. Two additional new MLST types were detected: ST 2306 and ST 2307. The presence of more than one PFGE and MLST type among Telr isolates suggests that the capability for expressing TEL resistance has arisen several times in S. pneumoniae. It is also likely that TEL resistance is an older phenomenon and would not have been caused by TEL selection pressure, because all of our strains were collected in 2002, just before TEL was introduced into clinical practice in Finland. The fact that all of our isolates were of clinical origin means that this type of resistance can survive in the bacterial population and cause diseases to humans. It is also noticeable that six of these isolates were from invasive infections. Our results indicate that pneumococci with heterogeneous TEL resistance can be found in other countries, because many of our strains belonged to global clones. However, this resistance type is difficult to detect using the dilution method (8). We recommend that routine testing of TEL susceptibility of pneumococci be done with the disc diffusion method in a 5%-CO2 atmosphere, especially in areas where erm(B) is a common resistance mechanism.