Epidemiology of Mycoplasma pneumoniae Infections in Japan and Therapeutic Strategies for Macrolide-Resistant M. pneumoniae

Abstract

Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae pneumonia) is a major cause of community-acquired pneumonia worldwide. The surveillance of M. pneumoniae pneumonia is important for etiological and epidemiological studies of acute respiratory infections. In Japan, nation-wide surveillance of M. pneumoniae pneumonia has been conducted as a part of the National Epidemiological Surveillance of Infectious Diseases (NESID) program. This surveillance started in 1981, and significant increases in the numbers of M. pneumoniae pneumonia patients were noted in 1984, 1988, 2006, 2010, 2011, 2012, and 2015. The epidemics in 2011 and 2012 were particularly widespread and motivated researchers to conduct detailed epidemiological studies, including genotyping and drug resistance analyses of M. pneumoniae isolates. The genotyping studies based on the p1 gene sequence suggested that the p1 gene type 1 lineage has been dominant in Japan since 2003, including the epidemic period during 2011–2012. However, more detailed p1 typing analysis is required to determine whether the type 2 lineages become more relevant after the dominance of the type 1 lineage. There has been extensive research interest in implications of the p1 gene types on the epidemiology of M. pneumoniae infections. Serological characterizations of sera from patients have provided a glimpse into these associations, showing the presence of type specific antibody in the patient sera. Another important epidemiological issue of M. pneumoniae pneumonia is the emergence of macrolide-resistant M. pneumoniae (MRMP). MRMPs were noted among clinical isolates in Japan after 2000. At present, the isolation rate of MRMPs from pediatric patients is estimated at 50–90% in Japan, depending on the specific location. In view of the situation, Japanese societies have issued guiding principles for treating M. pneumoniae pneumonia. In these guiding principles, macrolides are still recommended as the first-line drug, however, if the fever does not subside in 48–72 h from first-line drug administration, a change of antibiotics to second-line drugs is recommended.

Multiple-Locus Variable-Number Tandem-Repeat Analysis of <i>Mycoplasma pneumoniae</i> Isolates between 2004 and 2014 in Yamagata, Japan: Change in Molecular Characteristics during an 11-year Period

“…This and several previous studies demonstrated that most strains of MLVA type 3-5-6-2 were P1 type 2 or its variant, whereas MLVA type 4-5-7-2 was P1 type 1 (9,(11)(12)(13)21,30). Therefore, the increase in MLVA type 3-5-6-2 after 2011 may be a type-shift phenomenon of M. pneumoniae P1 types (7).…”

“…Epidemics of M. pneumoniae infections have been observed in 3-to 7-year intervals in many areas worldwide (7). In Japan, a large epidemic of M. pneumoniae infections was observed between 2011 and 2013 (29).…”

“…Multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) was developed by Dégrange et al (6) as a molecular typing method to compensate for P1 gene typing, the most common typing method for M. pneumoniae based on polymorphisms in the P1 gene encoding M. pneumoniae P1 adhesion protein (7). Although 5-locus MLVA (Mpn1, Mpn13-16) was reported by Dégrange et al (6), exclusion of the Mpn 1 locus in future analysis is recommended because of its instability (8).…”

“…pneumoniae infections can be treated with macrolides as first-line antibiotics (18,19). However, the prevalence of macrolide-resistant M. pneumoniae infections has increased since the year 2000, particularly in eastern Asian countries such as Japan and China (7). Since then, macrolide-resistant M. pneumoniae infections have spread worldwide, contributing to increasing global public health concerns (7,18).…”

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 .…”