Drug Resistance Mechanisms ofMycoplasma pneumoniaeto Macrolide Antibiotics

Abstract

Throat swabs from children with suspected Mycoplasma pneumoniae (M. pneumoniae) infection were cultured for the presence of M. pneumoniae and its species specificity using the 16S rRNA gene. Seventy-six M. pneumoniae strains isolated from 580 swabs showed that 70 were erythromycin resistant with minimum inhibitory concentrations (MIC) around 32–512 mg/L. Fifty M. pneumoniae strains (46 resistant, 4 sensitive) were tested for sensitivity to tetracycline, ciprofloxacin, and gentamicin. Tetracycline and ciprofloxacin had some effect, and gentamicin had an effect on the majority of M. pneumoniae strains. Domains II and V of the 23S rRNA gene and the ribosomal protein L4 and L22 genes, both of which are considered to be associated with macrolide resistance, were sequenced and the sequences were compared with the corresponding sequences in M129 registered with NCBI and the FH strain. The 70 resistant strains all showed a 2063 or 2064 site mutation in domain V of the 23S rRNA but no mutations in domain II. Site mutations of L4 or L22 can be observed in either resistant or sensitive strains, although it is not known whether this is associated with drug resistance.

Epidemiology and mechanism of drug resistance of Mycoplasma pneumoniae in Beijing, China: A multi-center study

“…Culture of M. pneumoniae was performed using PPLO (pleuropneumonia-like organisms) basic medium (BD-Difco, USA) containing 15% newborn calf serum, 10% fresh yeast extract (OXOID, UK), 0.4% phenol red indicator (Sigma, USA), 1% glucose, and 50000 U/100 mL penicillin, as described previously [21]. Tracheal swab specimens were inoculated on the M. pneumoniae liquid medium and maintained in an incubator at 37°C with a 5% CO 2 atmosphere.…”

“…Mutations in domain V of the 23S rRNA gene are the main cause of macrolides resistance, especially those at positions 2063 and 2064. Many studies have revealed that macrolides could inhibit protein synthesis by binding to large ribosomal subunits, so mutations in 23S rRNA may lead to decreased affinity of the ribosome for drug [21]. While many reports have investigated the role of the mutation in domain V of 23S rRNA gene, no study has analyzed mutations in the ribosomal proteins L4 and L22 [36].…”

“…Although M. pneumoniae is sensitive to macrolide, tetracycline, and quinolone antibiotics, which affect the synthesis of proteins and nucleic acids, macrolides remain the first choice for the treatment of M. pneumoniae infection in children [19]. However, the phenomenon of M. pneumoniae resistance continues to increase worldwide, especially in China and Japan, where the resistance rate is reported to be over 90% [20,21]. Since 2004, tetracycline and quinolone antibiotics have been approved for use in children over eight years of age with macrolide resistance or refractory M. pneumoniae infection [22].…”

Regional Differences in Prevalence of Macrolide Resistance among Pediatric <i>Mycoplasma pneumoniae</i> Infections in Hokkaido, Japan

“…Since approximately the year 2000, macrolide-resistant (MR) M. pneumoniae has been appearing in Asia, Europe, Canada, and the USA (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The rate of macrolide resistance among M. pneumoniae infections ranges from 3 to 26z in Europe (9,15), from 63 to 97z in China (16)(17)(18)(19), and from 25 to 93z in Japan (20)(21)(22). The total number of febrile days and the number of febrile days during macrolide administration are greater in patients infected with MR M. pneumoniae than in patients infected with macrolide-sensitive (MS) M. pneumoniae (23).…”

Lipid moieties of Mycoplasma pneumoniae lipoproteins are the causative factor of vaccine-enhanced disease

“…Mycoplasma pneumoniae (Mp) is a highly contagious and widespread human respiratory pathogen causing over 2 million cases of community-acquired pneumonia (CAP) and~100,000 adult hospitalizations annually in the United States 1 . Additionally, innate resistance to commonly used β-lactam antibiotics, increasing resistance to macrolide antibiotics, and mortality in certain demographic groups establish Mp as a high-risk pathogen capable of causing acutely severe disease [2][3][4][5][6][7] . Critically, no vaccine against Mp is available, as experimental vaccine-enhanced disease (VED) after infection has stymied further development.…”