An Overview of Macrolide Resistance in Streptococci: Prevalence, Mobile Elements and Dynamics

Abstract

Streptococcal infections are usually treated with beta-lactam antibiotics, but, in case of allergic patients or reduced antibiotic susceptibility, macrolides and fluoroquinolones are the main alternatives. This work focuses on studying macrolide resistance rates, genetic associated determinants and antibiotic consumption data in Spain, Europe and also on a global scale. Macrolide resistance (MR) determinants, such as ribosomal methylases (erm(B), erm(TR), erm(T)) or active antibiotic efflux pumps and ribosomal protectors (mef(A/E)-mrs(D)), are differently distributed worldwide and associated with different clonal lineages and mobile genetic elements. MR rates vary together depending on clonal dynamics and on antibiotic consumption applying selective pressure. Among Streptococcus, higher MR rates are found in the viridans group, Streptococcus pneumoniae and Streptococcus agalactiae, and lower MR rates are described in Streptococcus pyogenes. When considering different geographic areas, higher resistance rates are usually found in East-Asian countries and milder or lower in the US and Europe. Unfortunately, the availability of data varies also between countries; it is scarce in low- and middle- income countries from Africa and South America. Thus, surveillance studies of macrolide resistance rates and the resistance determinants involved should be promoted to complete global knowledge among macrolide resistance dynamics.

Serotype distribution, antimicrobial susceptibility and molecular epidemiology of invasive Streptococcus pneumoniae in the nine-year period in Serbia

“…In contrast, the M-phenotype associated with the mef genes was the predominant resistance mechanism in some European countries (Austria, Bulgaria, Ireland, Finland, Germany, Greece, United Kingdom) and the United States in the pre-PCV period ( Farrell et al, 2008 ; Siira et al, 2009 ; Bley et al, 2011 ; Setchanova et al, 2012 ). In the present study, the simultaneous presence of both mef and erm genes was detected in 16.6% of the isolates, which is higher than the mean European value (6.1%) at that time ( Berbel et al, 2022 ). However, 5% of the tested macrolide-resistant isolates were negative for both genes, indicating the possibility of other resistance mechanisms such as L4 and L22 ribosomal protein mutations, or the presence of other mef and erm gene variants ( Nagai et al, 2002 ; Midouni Ayadi et al, 2020 ), but additional research is warranted.…”

Serotype, antibiotic susceptibility and whole-genome characterization of Streptococcus pneumoniae in all age groups living in Southwest China during 2018–2022

“…Macrolides and fluoroquinolones are the main alternatives to beta-lactam antibiotics in cases of reduced susceptibility to S. pneumoniae infections ( Berbel et al, 2022 ). However, with widespread clinical use of macrolide antibacterial agents, the number of ERY-resistant S. pneumoniae (ERSP) strains has increased.…”

Structure Elucidation and Interaction Dynamics of MefA-MsrD Efflux Proteins in Streptococcus pneumoniae: Impact on Macrolide Susceptibility

“…Macrolide resistance from mef ( A / E ) in S. pyogenes was also considerably high in Africa (>48%), Europe (>40%), and Asia (∼40%). 23 It was discovered that the mef ( A ) – msr ( D ) tandem is a required hallmark for the development of an active efflux transport system. The mefA / E and msrD genes are typically present in an operon located in the MEGA.…”