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Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Macrolide resistance in Mycoplasma pneumoniae in adult patients
Panpan Xie1,2, Yue Zhang1,3, Yanhong Qin1,3
1Department of Respiratory and Critical Care Medicine, Senior Department of Infectious Diseases, the Fifth Medical Center of PLA General Hospital, Beijing, China.
Abstract:
Mycoplasma pneumoniae is one of the most significant pathogens responsible for respiratory infections in humans. Macrolides are recommended as the first-line treatment for M. pneumoniae infection. The prevalence of macrolide-resistant M. pneumoniae has increased significantly in recent decades, particularly in China. The mechanisms of resistance in M. pneumoniae 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 M. pneumoniae 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 M. pneumoniae strains. The antimicrobial susceptibility of these isolates to 3 macrolide antibiotics was assessed using broth microdilution method. The 23S rRNA genes of macrolide-resistant M. pneumoniae strains were sequenced, and the presence of target methylation genes (ermA, ermB, and ermC), efflux pump genes (mefA, mefA/E, msrA, and msrA/B), and the macrolide resistance gene mphC was identified through polymerase chain reaction (PCR) testing. Additionally, MICs were determined with and without the efflux pump inhibitor reserpine. A total of 72 M. pneumoniae 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 M. pneumoniae. All macrolide-resistant M. pneumoniae strains harbored mutations at the 2063 site in domain V of the 23S rRNA gene. Two macrolide-resistant M. pneumoniae clinical isolates were found to harbor the efflux pump genes msrA/B and mefA. 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 M. pneumoniae is commonly observed among adults in Beijing. Point mutations are the primary mechanism responsible for macrolide resistance in adults with M. pneumoniae. Additionally, the efflux pump mechanism may contribute partially to this resistance. Midecamycin presents a promising alternative drug for treating M. pneumoniae infections, particularly in cases of azithromycin-resistant M. pneumoniae infection in young children.
Insights
Macrolide-resistant Mycoplasma pneumoniae is common in adults, primarily due to 23S rRNA gene mutations. Efflux pumps also contribute to resistance, suggesting midecamycin as a potential alternative treatment.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Mycoplasma pneumoniae causes significant respiratory infections.
- Macrolides are first-line treatments, but resistance is increasing.
- Resistance mechanisms in adults remain understudied compared to pediatric cases.
Purpose of the Study:
- To investigate macrolide resistance in M. pneumoniae from adult patients.
- To elucidate the underlying resistance mechanisms in adult isolates.
- To evaluate potential alternative treatments.
Main Methods:
- Collected pharyngeal swabs from adult patients with respiratory infections.
- Isolated and identified M. pneumoniae strains.
- Assessed antimicrobial susceptibility using broth microdilution.
- Sequenced 23S rRNA genes and performed PCR for resistance genes (erm, mef, mphC).
- Determined Minimum Inhibitory Concentrations (MICs) with and without reserpine.
Main Results:
- 41.7% of 72 M. pneumoniae isolates were macrolide-resistant.
- All resistant strains had mutations at the 2063 site in the 23S rRNA gene.
- Efflux pump genes (msrA/B, mefA) were found in two isolates.
- Reserpine reduced azithromycin MICs by 75% in these two strains.
- Midecamycin showed the greatest activity against M. pneumoniae (MIC90: 16 µg/ml).
Conclusions:
- Macrolide-resistant M. pneumoniae is prevalent in adult patients in Beijing.
- Point mutations in the 23S rRNA gene are the primary resistance mechanism.
- Efflux pumps play a partial role in macrolide resistance.
- Midecamycin is a promising alternative for treating M. pneumoniae infections, especially azithromycin-resistant cases.
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