Abstract

Macrolides are often used to treat group A streptococcus (GAS) infections, but their resistance rates reached high proportions worldwide. The aim of the present study was to give an update on the characteristics and contemporary prevalence of macrolide-resistant pharyngeal GAS in Central Italy. A total of 592 isolates causing pharyngitis in children were collected in the period 2012–2013. Clonality was assessed by emm typing and pulsed-field gel electrophoresis (PFGE) for all macrolide-resistant strains and for selected susceptible isolates. Genetic determinants of resistance were screened by polymerase chain reaction (PCR). Forty-four GAS were erythromycin-resistant (7.4 %). Among them, 52.3 % and 50 % were clindamycin- and tetracycline-resistant, respectively. erm(B)-positive isolates (52.3 %) expressed the constitutive cMLSB phenotype. mef(A) and its associated M phenotype were recorded in 40.9 % of the cases. The remaining erm(A)-positive isolates expressed the iMLSB phenotype. Seventeen tetracycline-resistant isolates carried tet(M) and five isolates carried tet(O). Twenty-five emm types were found among all strains, with the predominance of emm types 12, 89, 1, and 4. Eleven emm types and 12 PFGE clusters characterized macrolide-resistant strains, with almost two-thirds belonging to emm12, emm4, and emm11. Macrolide-susceptible and -resistant emm types 12, 89, 11, and 4 shared related PFGE profiles. There was a dramatic decline in macrolide resistance in Central Italy among pharyngeal GAS isolates in 2012–2013 when compared to previous studies from the same region (p < 0.05), although macrolide consumption remained stable over the past 15 years. We observed a decrease in the proportion of macrolide-resistant strains within emm types commonly associated with macrolide resistance in the past, namely emm12, 1, and 89.

Highlights

  • Streptococcus pyogenes, or Lancefield group A streptococcus (GAS), is an important pathogen implicated in a wide variety of human infections

  • Macrolides have been recommended for patients allergic to β-lactams, and clindamycin is the preferred antibiotic in the treatment of patients with serious soft-tissue infections because of its ability to inhibit the production of several streptococcal virulence factors [1]

  • All resistant GAS were uniformly susceptible to all antibiotics tested except for clindamycin (52.3 %) and tetracycline (50 %)

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Summary

Introduction

Streptococcus pyogenes, or Lancefield group A streptococcus (GAS), is an important pathogen implicated in a wide variety of human infections. Macrolides have been recommended for patients allergic to β-lactams, and clindamycin is the preferred antibiotic in the treatment of patients with serious soft-tissue infections because of its ability to inhibit the production of several streptococcal virulence factors [1]. Resistance to erythromycin and related antibiotics has represented an important cause of concern [2, 3] and is mainly associated with two mechanisms. The second mechanism involves erm genes, including erm(A) [subclass erm(TR)] and erm(B), which encode methylases targeting 23S rRNA [5]. Other less common mechanisms of macrolide resistance are associated with mutations in the 23S rRNA gene sequence and/or alterations in riboproteins L4 and L22 [5]. An association between erythromycin resistance and cell invasiveness has been observed [6]

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