Resistance Determinants and Clonal Diversity in Group A Streptococci Collected during a Period of Increasing Macrolide Resistance

Abstract

Susceptibility to macrolides and lincosamides was investigated with 299 consecutive nonduplicate Streptococcus pyogenes clinical isolates collected over a 6-year period (1992 to 1997) from an area of central Italy. During this period, macrolide resistance rates steadily increased (from 9% in 1992 to 53% in 1997; P < 0.001). The increase was caused by isolates with a macrolide-lincosamide-streptogramin B resistance phenotype, carrying mostly erm(B) but also erm(TR) genes, that were not detected in the first 2 years and were detected with increasing prevalence (8, 5, 26, and 37%, respectively) during the following 4 years. During the same period, the prevalence of isolates with a macrolide resistance phenotype, carrying mef(A) determinants, did not vary significantly; on average it was 13%, with modest rate fluctuations in different years and no definite trend. Molecular typing revealed a remarkable clonal diversity among susceptible and resistant isolates and a notable heterogeneity of the genetic environment of the resistance genes. The analysis of clonal diversity in relation with resistance phenotypes and genotypes revealed that increased macrolide resistance rates were due to a complex interplay of different mechanisms, with a relevant contribution played by an "epidemic" spread of genetic elements carrying the erm(B) gene among the circulating streptococcal population.Streptococcus pyogenes (group A streptococcus) remains one of the leading bacterial pathogens worldwide. Superficial infections caused by group A streptococci, such as pharyngitis and impetigo, are usually mild and self-limiting but ubiquitous and extremely common. On the other hand, the occurrence of severe invasive infections and of nonsuppurative sequelae, although less common, make of S. pyogenes a major public health concern (see reference 3 and references therein).Macrolide antibiotics are among the preferred drugs for the treatment of group A streptococcal pharyngitis and are largely used in community medicine for empirical chemotherapy of respiratory tract infections, due to their clinical efficacy, good compliance, and low toxicity (34). Resistance to macrolides in S. pyogenes can be caused by two different mechanisms: (i) active drug efflux via a transmembrane pump encoded by horizontally acquired mef genes (7, 35) and (ii) modification of the 23S rRNA target by rRNA adenine methylases encoded by horizontally acquired erm genes (see references 19 and 38 and references therein). The Mef efflux system operates only with 14-and 15-membered ring macrolides (M resistance phenotype) (7), while ribosomal modification by Erm methylases prevents the binding of macrolides, lincosamides, and streptogramins B, leading to resistance to all these compounds (MLS resistance phenotype) (19 (19,38,39).Since the first report in the 1950s (20), a large number of epidemiological surveys on macrolide resistance in S. pyogenes have been carried out. Results of these studies overall revealed a remarkable variability of resistance rates at different times and...

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

“…The rate of occurrence of multiple clones of M-phenotype GAS circulating simultaneously within a given geographic region is similar to data from most other centers (14,32). This might be explained by the transfer of the mef(A) gene between bacterial strains on a conjugative transposon (18,26).…”

Development of promiscous rhizobia for diverse rabi legumes (Chickpea, Pea and Lentil)

“…Earlier intrinsic antibiotic resistance pattern has been utilized to evaluate variability in rhizobia (Mishra et al, 1975;Jayachandran and Balasubramaniam, 1978;Vashishat and Yadav, 1985aand Eaglesham, 1987, Kawaharada et al, 2015. As noted in previous studies (Rasool, 2003 andCresti et al, 2002), there was a correlation between the antibiotic resistance phenotype and the genotype. In this study it was observed that there are variations between different bacterial strains in the antibiotic resistance.…”

Prevalence of Group A Streptococcal Carriers in Asymptomatic Children and Clonal Relatedness among Isolates in Malatya, Turkey

“…Although many investigators use the AP-PCR method in combination with PFGE for investigation of molecular epidemiology of GAS in a community (4,5,6,18), to date there have been no published data on the clonal diversity of S. pyogenes isolates obtained from asymptomatic carriers or symptomatic patients in Turkey. In our study, PFGE yielded 85 different patterns among 105 S. pyogenes isolates.…”

“…Study of the prevalence of healthy S. pyogenes carriers and the molecular epidemiology of the isolates may provide useful information about the origin and spread of this infectious agent, allowing for more effective control measures. Pulsed-field gel electrophoresis (PFGE) (3,4,14) has been used as a standard technique for surveying epidemiology of S. pyogenes infections. Although arbitrarily primed PCR (AP-PCR)-based fingerprinting performed with the M13 primer has been widely used for molecular epidemiology of gram-negative (1, 2, 10) and gram-positive bacteria (11), there had been no study about its efficiency in typing S. pyogenes strains.…”