Molecular Epidemiology of Multiresistant Streptococcus pneumoniae with Both erm (B)- and mef (A)-Mediated Macrolide Resistance

Abstract

Of a total of 1,043 macrolide-resistant Streptococcus pneumoniae isolates collected from 24 countries as part of PROTEKT 1999-2000, 71 isolates tested positive for both the mef(A) and erm(B) genes. Of 69 isolates subjected to further molecular investigations, all were resistant to tetracycline, 63 (91.3%) were resistant to penicillin, and 57 (82.6%) were resistant to trimethoprim-sulfamethoxazole. One isolate was also fluoroquinolone resistant, and another was resistant to quinupristin-dalfopristin. The ketolide telithromycin retained activity against all of the isolates. Of the 69 of these 71 isolates viable for further testing, 46 were from South Korea, 13 were from the United States, 8 came from Japan, and 1 each came from Mexico and Hungary. One major clonal complex (59 [85.5%] of 69 isolates) was identified by serotyping (with 85.5% of the isolates being 19A or 19F), pulsed-field gel electrophoresis, and multilocus sequence typing. The remaining isolates were less clonal in nature. Representative isolates were shown to carry the mobile genetic elements Tn1545 and mega, were negative for Tn1207.1, had tetracycline resistance mediated by tet(M), and contained the mef(E) variant of mef(A). All isolates were positive for mel, a homologue of the msr(A) efflux gene. These clones are obviously very efficient at global dissemination, and hence it will be very important to monitor their progress through continued surveillance. Telithromycin demonstrated high levels of activity (MIC for 90% of the strains tested, 0.5 g/ml; MIC range, 0.06 to 1 g/ml) against all isolates.

Prevalence and Molecular Analysis of Macrolide and Fluoroquinolone Resistance among Isolates of Streptococcus pneumoniae Collected during the 2000-2001 PROTEKT US Study

“…Isolates carrying both mef(A) and erm(B) have been reported previously (4,11,24) and are highly multidrug resistant (11), as the results of the present study have confirmed. This high-level resistance is most likely due to the presence of more than one mobile genetic element (11), but this hypothesis was not tested in the present study.…”

“…In Japan, isolates with the mef(A) (40.3%) and the erm(B) (43.5%) genes are equally prevalent, but isolates with both erm(B) and mef(A) are relatively common (16.1%) (30). Interestingly, most erm(B) mef(A) isolates appear to belong to a multidrug-resistant clonal complex (11). Telithromycin is one of the few antibacterials to have good activity against this clone (11).…”

“…Interestingly, most erm(B) mef(A) isolates appear to belong to a multidrug-resistant clonal complex (11). Telithromycin is one of the few antibacterials to have good activity against this clone (11). In this study, resistance to multiple antibacterial agents was shown to be highly prevalent among all erythromycin resistance genotypes, with the number of antibacterial agents to which isolates were resistant being higher for those that possessed the erm(B) gene or the erm(B) and the mef(A) genes.…”

Clonal Dissemination of Macrolide-Resistant and Penicillin-Susceptible Serotype 3 and Penicillin-Resistant Taiwan 19F-14 and 23F-15 Streptococcus pneumoniae Isolates in Japan: a Pilot Surveillance Study

“…In our study, we found one isolate that has both the mef(A)/ mef(E) and erm(B) genes and is closely related to Taiwan19F-14. Farrell et al have reported that such an isolate carries the mobile genetic elements Tn1545 and mega and suggested that the acquisition of such elements seems to be very effective in global dissemination (6). We therefore have to pay close attention to the increase of such isolates by continuous surveillance studies in Japan.…”

Genetic determinants of antibiotic resistance in oropharyngeal streptococci in patients with chronic obstructive pulmonary disease and in those with asthma

“…Кроме того, описаны генетические ме-ханизмы формирования устойчивости стрептококков к макролидам. Первый вариант реализуется за счет приоб-ретения гена ermB (erythromycin-resistance methylase), что приводит к фенотипической устойчивости к эритромици-ну, кларитромицину, азитромицину и к клиндамицину [13]. Другой путь связан с приобретением генов mef, коди-рующих зависимые от ATФ белки, активно выводящие антибиотики из бактериальной клетки.…”