Emergence of Macrolide-Resistant Mycoplasma pneumoniae in Hong Kong Is Linked to Increasing Macrolide Resistance in Multilocus Variable-Number Tandem-Repeat Analysis Type 4-5-7-2

Abstract

Macrolide-resistant Mycoplasma pneumoniae (MRMP) is rapidly emerging in Asia, but information on the temporal relationship between the increase in macrolide resistance and changes in strain types is scarce. Between 2011 and 2014, M. pneumoniae infection was diagnosed by PCR as part of routine care in a health care region in Hong Kong. Testing was initiated by clinicians, mainly in patients with suspected M. pneumoniae pneumonia. Specimens positive for M. pneumoniae were retrospectively investigated by macrolide resistance genotyping and a four-locus (Mpn13 to -16) multilocus variable-number tandem-repeat analysis (MLVA) scheme. The overall percentage of M. pneumoniae-positive specimens was 17.9%, with annual rates ranging from 9.8% to 27.2%. The prevalence of MRMP had rapidly increased from 13.6% in 2011 to 30.7% in 2012, 36.6% in 2013, and 47.1% in 2014 (P ‫؍‬ 0.038). Two major MLVA types, 4-5-7-2 and 3-5-6-2, accounted for 75% to 85% of the infections each year. MLVA types 4-5-7-2 and 3-5-6-2 predominated among macrolide-resistant and macrolide-sensitive groups, respectively. The increase in MRMP was mainly caused by increasing macrolide resistance in the prevalent MLVA type 4-5-7-2, changing from 25.0% in 2011 to 59.1% in 2012, to 89.7% in 2013, and to 100% in 2014 (P < 0.001). In conclusion, increasing MRMP in Hong Kong was linked to a single MLVA type, which was both prevalent and increasingly resistant to macrolides. Mycoplasma pneumoniae is a common cause of communityacquired pneumonia and other respiratory tract infections (1). Community epidemics occur at intervals of 3 to 7 years. Infections develop in persons of all ages, but it is primarily a disease of children and teenagers (2). When treatment is indicated, a macrolide is usually the drug of choice (1, 2). However, macrolideresistant M. pneumoniae (MRMP) has become increasingly prevalent worldwide, and high rates of infection (Ͼ80%) have been found in certain parts of the world (3-6). MRMP infections have been associated with persistence of symptoms, slower reduction in bacterial load, longer hospital stays, requirement of alternative therapy, and higher frequency of complications (1,7,8). Strain typing is important for understanding changes in disease epidemiology and for investigations of outbreaks. In 2009, a multilocus variable-number tandem-repeat analysis (MLVA) scheme based upon five loci (Mpn1 and Mpn13 to -16) was developed for the molecular typing of M. pneumoniae (9). It was initially used for an investigation of isolates but was later modified for directly typing M. pneumoniae in respiratory specimens (10-12). An amended 4-locus MLVA scheme was later proposed after studies raised concerns on the instability of the Mpn1 locus (13,14). In clinical laboratories, culture and characterization of M. pneumoniae are seldom performed. Therefore, M. pneumoniae typing was usually carried out on isolates collected from sporadic cases and outbreaks (9,13,15), limiting the inferences that can be made about trends in M. pneumoniae infections. In addit...

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

“…The proportions of MLVA and P1 types were reported to vary among geographic regions, as has the prevalence of macrolide resistance-associated mutations (9)(10)(11)20,21). We also reported P1 types and the prevalence of macrolide resistance-associated mutations of M. pneumoniae isolates in Yamagata, Japan between 2004 and 2013 (22).…”

“…MLVA types 4-5-7-2 and 3-5-6-2 were the predominant types in studies from various geographic regions (9)(10)(11)20,21,23 (20). Additionally, type 4-5-7-2 showed a 30 prevalence in various regions worldwide during a respective study period, including Tokyo, Japan (23); Hong Kong (10); Germany (21); and Australia (11).…”

The reduced prevalence of macrolide resistance inMycoplasma pneumoniaeclinical isolates from pediatric patients in Beijing in 2016

“…The macrolide resistance rate was 69.48% in pediatric patients with MP infection in Beijing, China in 2016. The macrolide resistance rates recently published were 100% in children of Zhejiang province, China in 2014 10 , 87.2% in South Korean children in 2015 17 , 43.6% in Japanese children in 2015 11 , 47.1% in children of Hong-Kong in 2014 18 , 13.2% in American children through 2012 to 2014 5 , 9.3% in English children between 2014 and 2015 19 . Compared with the above data, the prevalence of MRMP clinical isolates among children in China has significantly decreased to 69.48% from 80-100% 3,10,13 .…”

Comparative efficacy of Chinese herbal injections combined with azithromycin for mycoplasma pneumonia in children: A Bayesian network meta‐analysis of randomized controlled trials

“…Azithromycin, a macrolide antibiotic, is a preferred decision because of its long half‐life and clear target‐cell effect . However, macrolide resistance has emerged worldwide with a significant increase, which increasingly lead to complex clinical treatment schemes . In recent years, with the increase of people’ recognition of traditional Chinese medicine, combining Chinese Medicine and Western Medicine to treat diseases has been an acceptable treatment method .…”

“…10 However, macrolide resistance has emerged worldwide with a significant increase, which increasingly lead to complex clinical treatment schemes. 2,[11][12][13][14][15] In recent years, with the increase of people' recognition of traditional Chinese medicine, combining Chinese Medicine and Western Medicine to treat diseases has been an acceptable treatment method. 16,17 This provides another idea to treat mycoplasma pneumonia in children.…”