AUTHOR=El Mammery Achraf , Ramírez de Arellano Eva , Cañada-García Javier E. , Cercenado Emilia , Villar-Gómara Laura , Casquero-García Verónica , García-Cobos Silvia , Lepe José Antonio , Ruiz de Gopegui Bordes Enrique , Calvo-Montes Jorge , Larrosa Escartín Nieves , Cantón Rafael , Pérez-Vázquez María , Aracil Belén , Oteo-Iglesias Jesús 

TITLE=An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004–2020)

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1220286

DOI=10.3389/fmicb.2023.1220286

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Objectives</title><p>To describe and analyse erythromycin resistance trends in blood isolates of <italic>Staphylococcus aureus</italic> (EARS-Net Spain, 2004–2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLS<sub>B</sub>) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates.</p></sec><sec id="sec2"><title>Materials and methods</title><p>We collected antibiotic susceptibility data for all first-blood <italic>S. aureus</italic> isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLS<sub>B</sub> antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008–2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis.</p></sec><sec id="sec3"><title>Results</title><p>For the 36,612 invasive <italic>S. aureus</italic> isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible <italic>S. aureus</italic> (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (<italic>p</italic> &lt; 0.001); however, it decreased from 68.7 to 61.8% (<italic>p</italic> &lt; 0.0001) in methicillin-resistant <italic>S. aureus</italic> (MRSA). Total consumption of MLS<sub>B</sub> antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were <italic>erm</italic> (59.8%), <italic>msrA</italic> (46%), and <italic>mphC</italic> (45.2%). The <italic>erm</italic> genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the <italic>erm</italic> genes identified in MSSA after 2013 differed from the predominant <italic>ermC</italic> gene (17/22, 77.3%), largely because <italic>ermT</italic> was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 <italic>ermT</italic> isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces.</p></sec><sec id="sec4"><title>Conclusion</title><p>The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLS<sub>B</sub> antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with <italic>ermT</italic>-mediated resistance to erythromycin may be involved in this trend.</p></sec>