Genotypes and Related Factors Reflecting Macrolide Resistance in Pneumococcal Pneumonia Infections in Japan

Abstract

Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermBpositive pneumococcal pneumonia (odds ratio [OR] ‫؍‬ 11.1; 95% confidence interval [CI] ‫؍‬ 1.30 to 95.0; P ‫؍‬ 0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB-and mefA-positive isolates (OR ‫؍‬ 14.2; 95% CI ‫؍‬ 4.27 to 46.9; P < 0.0001 and P < 0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.

Clinical features and seasonal variations in the prevalence of macrolide‐resistant Mycoplasma pneumoniae

“…Excessive use of macrolides and quinolones for respiratory infections has been a major concern in Japan,28 because of their possible association to high macrolide resistance rates among Streptococcus pneumoniae 29 and M. pneumoniae ,7 and increased quinolone resistance among Enterobacteriaceae 30. Besides the reduction in antibiotic use, we consider that rapid diagnoses and early initiation of effective treatment may prevent the transmission of M. pneumoniae and consequently reduce the spread of macrolide‐resistant M. pneumoniae .…”

Serotype Replacement in Adult Pneumococcal Pneumonia after the Introduction of Seven-Valent Pneumococcal Conjugate Vaccines for Children in Japan: a Systematic Literature Review and Pooled Data Analysis

“…One of the prospective surveillance studies of the LRTI referred to the Japanese Respiratory Society (JRS) guidelines for the management of community-acquired pneumonia in adults (36) as diagnostic criteria for LRTI (17). Another 3 prospective surveillance studies of pneumonia also used similar case definitions to the JRS guidelines (1,18,19). All the laboratory-based pneumococcal strain surveillance studies were designed to test the collected pneumococcal strains from various specimens such as sputum, respiratory tract aspirates, nasopharyngeal swabs, eye or ear discharge, blood, cerebrospinal fluid, and pleural fluid.…”

“…All of the studies were performed in the pre-PCV13 period. The study designs could be categorized into case series of pneumococcal LRTI (15,16), prospective surveillance of pneumococcal LRTI or IPD cases (1,(17)(18)(19)(20), and laboratory-based pneumococcal strain surveillance (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). One of the prospective surveillance studies of the LRTI referred to the Japanese Respiratory Society (JRS) guidelines for the management of community-acquired pneumonia in adults (36) as diagnostic criteria for LRTI (17).…”

Efficacy of Azithromycin in the Treatment of Community-acquired Pneumonia, Including Patients with Macrolide-Resistant Streptococcus pneumoniae Infection

“…While the former mechanism appears to gives rise to high-level macrolide resistance (erythromycin MIC 128 μg/mL), the latter gives rise to lower-level resistance (erythromycin MIC 1 to 64 μg/mL) (7). In Japan, macrolide resistance among S. pneumoniae is now very common and is mediated predominantly by the ermB gene; in a recent study, 81.4% of S. pneumoniae isolates were resistant to erythromycin, and 50% possessed the ermB gene (12) (18,19 • Received drug for a condition other than CAP (n = 2)…”

“…In recent years, there has been an increasing worldwide problem of drug resistance among respiratory pathogens, notably S. pneumoniae which has shown increasing levels of penicillin and macrolide resistance (10)(11)(12)(13) (1,6,7). Resistance to macrolides among strains of S. pneumoniae is caused by two principal mechanisms: 1) methylation of a ribosomal binding site, which is encoded by the ermB gene; and 2) active drug efflux via a cell membrane protein transporters, which is encoded by the mefA gene (14).…”