Macrolide resistance in Mycoplasma pneumoniae in adult patients

<i>Mycoplasma pneumoniae</i> is one of the most significant pathogens responsible for respiratory infections in humans. Macrolides are recommended as the first-line treatment for <i>M. pneumoniae</i> infection. The prevalence of macrolide-resistant <i>M. pneumoniae</i> has increased significantly in recent decades, particularly in China. The mechanisms of resistance in <i>M. pneumoniae</i> to macrolides have been extensively studied in pediatric patients. However, a paucity reports regarding the resistance characteristics and mechanisms exhibited in adults. The aim of this study was to elucidate the resistance of <i>M. pneumoniae</i> to macrolides and the underlying mechanisms in adult patients. Pharyngeal swab specimens were collected from adult patients presenting with subacute cough or community-acquired pneumonia at our hospital from January 2011 to June 2017 to identify and isolate <i>M. pneumoniae</i> strains. The antimicrobial susceptibility of these isolates to 3 macrolide antibiotics was assessed using broth microdilution method. The <i>23S rRNA</i> genes of macrolide-resistant <i>M. pneumoniae</i> strains were sequenced, and the presence of target methylation genes (<i>ermA</i>, <i>ermB</i>, and <i>ermC</i>), efflux pump genes (<i>mefA</i>, <i>mefA/E</i>, <i>msrA</i>, and <i>msrA/B</i>), and the macrolide resistance gene <i>mphC</i> was identified through polymerase chain reaction (PCR) testing. Additionally, MICs were determined with and without the efflux pump inhibitor reserpine. A total of 72 <i>M. pneumoniae</i> strains were isolated from adult patients, with 41.7% (30/72) exhibiting macrolide resistance. Among the 3 macrolides tested, the 16-membered-ring midecamycin exhibited the greatest activity (MIC₉₀: 16 µg/ml) against <i>M. pneumoniae</i>. All macrolide-resistant <i>M. pneumoniae</i> strains harbored mutations at the 2063 site in domain V of the <i>23S rRNA</i> gene. Two macrolide-resistant <i>M. pneumoniae</i> clinical isolates were found to harbor the efflux pump genes <i>msrA/B</i> and <i>mefA</i>. The efflux pump inhibitor reserpine reduced the MIC for azithromycin in these two strains to a quarter of their original values. In summary, macrolide-resistant <i>M. pneumoniae</i> is commonly observed among adults in Beijing. Point mutations are the primary mechanism responsible for macrolide resistance in adults with <i>M. pneumoniae</i>. Additionally, the efflux pump mechanism may contribute partially to this resistance. Midecamycin presents a promising alternative drug for treating <i>M. pneumoniae</i> infections, particularly in cases of azithromycin-resistant <i>M. pneumoniae</i> infection in young children.