The molecular characteristics, diagnosis, and treatment of macrolide-resistant Mycoplasma pneumoniae in children

The purpose of this study is to review the molecular characteristics, the diagnosis, and treatment of the widespread infection of macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae; MRMP) in children, thus providing a better knowledge of this infection and presenting the associated problems. Single point mutations in the V region of the 23S rRNA gene of M. pneumoniae genome are associated with macrolide resistance. P1–1, MLVA4-5-7-2, and ST3 are usually the predominated genetic types in the M. pneumoniae epidemics. The short-term two times serological IgM (or together with IgG) test in the acute stage can be used for confirmation. Combined serological testing and PCR might be a more prudent method to reduce macrolide consumption and antibiotic selective pressure in a clinical setting. Molecular methods for the detection of single-nucleotide mutations in the V region of the 23S rRNA gene can be used for the diagnosis of MRMP. The routine use of macrolide for the treatment of macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections can get good effect, but the effects are limited for severe MRMP infections. Additional corticosteroids may be required for the treatment of severe MRMP infections in children in China during the era of MRMP.

[1]  Kyung-Yil Lee Common immunopathogenesis of central nervous system diseases: the protein-homeostasis-system hypothesis , 2022, Cell & Bioscience.

[2]  Jung-Woo Rhim,et al.  Etiological and pathophysiological enigmas of severe coronavirus disease 2019, multisystem inflammatory syndrome in children, and Kawasaki disease , 2021, Clinical and experimental pediatrics.

[3]  C. Berger,et al.  Mycoplasma pneumoniae Genotypes and Clinical Outcome in Children , 2021, Journal of clinical microbiology.

[4]  H. Cho Consideration in treatment decisions for refractory Mycoplasma pneumoniae pneumonia , 2021, Clinical and experimental pediatrics.

[5]  H. Kang,et al.  Early Confirmation of Mycoplasma pneumoniae Infection by Two Short-Term Serologic IgM Examination , 2021, Diagnostics.

[6]  Jianzhong Zhang,et al.  First report of macrolide resistant and susceptible Mycoplasma pneumoniae clinical strains isolated from one case. , 2021, Journal of global antimicrobial resistance.

[7]  F. Dai,et al.  The treatment of macrolide‐resistant Mycoplasma pneumoniae pneumonia in children , 2020, Journal of clinical pharmacy and therapeutics.

[8]  W. Zhou,et al.  Mycoplasma pneumoniae Macrolide Resistance and MLVA Typing in Children in Beijing, China, in 2016: Is It Relevant? , 2020, Biomedical and environmental sciences : BES.

[9]  C. Chiu,et al.  Clonal spread of macrolide-resistant Mycoplasma pneumoniae sequence type-3 and type-17 with recombination on non-P1 adhesin among children in Taiwan. , 2020, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[10]  L. Bachmann,et al.  Evaluation of IgM Lateral Flow Assay as a Screening Tool for Mycoplasma pneumoniae Infection in Childhood Pneumonia , 2020, Journal of Clinical Microbiology.

[11]  Steven D. Dallas,et al.  Molecular Characterization of Mycoplasma pneumoniae Isolates in the United States from 2012 to 2018 , 2020, Journal of Clinical Microbiology.

[12]  H. Ohya,et al.  Periodic Genotype Shifts in Clinically Prevalent Mycoplasma pneumoniae Strains in Japan , 2020, Frontiers in Cellular and Infection Microbiology.

[13]  L. Matas,et al.  Macrolide resistance and molecular typing of Mycoplasma pneumoniae infections during a 4 year period in Spain , 2020, The Journal of antimicrobial chemotherapy.

[14]  Tu-Hsuan Chang,et al.  Macrolide-Resistant Mycoplasma pneumoniae Infections in Pediatric Community-Acquired Pneumonia , 2020 .

[15]  Jung-Woo Rhim,et al.  Immunopathogenesis of COVID-19 and early immunomodulators , 2020, Clinical and experimental pediatrics.

[16]  Kyung-Yil Lee,et al.  Are alternative antibiotics needed for antibiotic-nonresponsive Mycoplasma pneumoniae pneumonia? , 2020, Clinical and experimental pediatrics.

[17]  Ting-Yu Yen,et al.  Multiple-locus variable-number tandem-repeat analysis (MLVA) of macrolide-susceptible and -resistant Mycoplasma pneumoniae in children in Taiwan. , 2020, Journal of the Formosan Medical Association = Taiwan yi zhi.

[18]  J. Cui,et al.  Diversity in Genotype Distribution of Mycoplasma pneumoniae Obtained from Children and Adults. , 2020, Japanese journal of infectious diseases.

[19]  Yindong Li,et al.  Outbreak of macrolide-resistant mycoplasma pneumoniae in a primary school in Beijing, China in 2018 , 2019, BMC Infectious Diseases.

[20]  Jinrong Liu,et al.  Antimicrobial susceptibility and molecular characteristics of Mycoplasma pneumoniae isolates across different regions of China , 2019, Antimicrobial Resistance & Infection Control.

[21]  H. Kang,et al.  Early Corticosteroid Therapy for Mycoplasma pneumoniae Pneumonia Irrespective of Used Antibiotics in Children , 2019, Journal of clinical medicine.

[22]  T. Kenri,et al.  Genetic characterization of Mycoplasma pneumoniae isolated in Osaka between 2011 and 2017: Decreased detection rate of macrolide-resistance and increase of p1 gene type 2 lineage strains , 2019, PloS one.

[23]  Jinrong Liu,et al.  Antimicrobial susceptibility and genotyping of Mycoplasma pneumoniae isolates in Beijing, China, from 2014 to 2016 , 2019, Antimicrobial Resistance & Infection Control.

[24]  Y. Adachi,et al.  Multilocus Sequence Typing of Mycoplasma pneumoniae, Japan, 2002–2016 , 2018, Emerging infectious diseases.

[25]  Y. Ahn,et al.  Clonal Expansion of Macrolide-Resistant Sequence Type 3 Mycoplasma pneumoniae, South Korea , 2018, Emerging infectious diseases.

[26]  Q. Shu,et al.  Mycoplasma pneumoniae induces allergy by producing P1-specific immunoglobulin E. , 2018, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[27]  Hyunju Lee,et al.  Antimicrobial therapy of macrolide-resistant Mycoplasma pneumoniae pneumonia in children , 2018, Expert review of anti-infective therapy.

[28]  Z. Rueda,et al.  Genotyping and macrolide resistance of Mycoplasma pneumoniae identified in children with community-acquired pneumonia in Medellín, Colombia , 2017, International Journal of Infectious Diseases.

[29]  S. Hongo,et al.  Development of macrolide resistance‐associated mutations after macrolide treatment in children infected with Mycoplasma pneumoniae , 2017, Journal of medical microbiology.

[30]  Ki Bae Hong,et al.  Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia , 2017, BMC Infectious Diseases.

[31]  H. Yang,et al.  Mechanism of resistance acquisition and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children , 2017, Korean journal of pediatrics.

[32]  Mitchell F. Balish,et al.  Mycoplasma pneumoniae from the Respiratory Tract and Beyond , 2017, Clinical Microbiology Reviews.

[33]  Jianming Zhou,et al.  Utility of Assessing Cytokine Levels for the Differential Diagnosis of Pneumonia in a Pediatric Population* , 2017, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[34]  Lilian X. L. Chen,et al.  Clinical analysis of mycoplasma pneumoniae pneumonia with 23SrRNA A2063G gene mutation in 24 cases , 2017 .

[35]  W. H. Seo,et al.  Macrolide Resistance and Its Impacts on M. Pneumoniae Pneumonia in Children: Comparison of Two Recent Epidemics in Korea , 2017, Allergy, asthma & immunology research.

[36]  Q. Ye,et al.  Meteorological factors on the incidence of MP and RSV pneumonia in children , 2017, PloS one.

[37]  G. Xue,et al.  Changes in Molecular Characteristics of Mycoplasma pneumoniae in Clinical Specimens from Children in Beijing between 2003 and 2015 , 2017, PloS one.

[38]  S. Hongo,et al.  Development of an endpoint genotyping assay to detect the Mycoplasma pneumoniae 23S rRNA gene and distinguish the existence of macrolide resistance-associated mutations at position 2063. , 2016, Journal of microbiological methods.

[39]  Wei‐Ju Lee,et al.  Role of Serum Mycoplasma pneumoniae IgA, IgM, and IgG in the Diagnosis of Mycoplasma pneumoniae-Related Pneumonia in School-Age Children and Adolescents , 2016, Clinical and Vaccine Immunology.

[40]  T. Kenri,et al.  Epidemiology of Mycoplasma pneumoniae Infections in Japan and Therapeutic Strategies for Macrolide-Resistant M. pneumoniae , 2016, Front. Microbiol..

[41]  Sung-Churl Lee,et al.  Early Serologic Diagnosis of Mycoplasma pneumoniae Pneumonia: An Observational Study on Changes in Titers of Specific-IgM Antibodies and Cold Agglutinins , 2016, Medicine.

[42]  Maureen H Diaz,et al.  The Evolution of Advanced Molecular Diagnostics for the Detection and Characterization of Mycoplasma pneumoniae , 2016, Front. Microbiol..

[43]  María Lluch-Senar,et al.  Comparative “-omics” in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors , 2015, PloS one.

[44]  J. D. Osborne,et al.  Comparative genome analysis of Mycoplasma pneumoniae , 2015, BMC Genomics.

[45]  M. Holden,et al.  Development of a Multilocus Sequence Typing Scheme for Molecular Typing of Mycoplasma pneumoniae , 2015, Journal of Clinical Microbiology.

[46]  Maureen H Diaz,et al.  Molecular Detection and Characterization of Mycoplasma pneumoniae Among Patients Hospitalized With Community-Acquired Pneumonia in the United States , 2015, Open forum infectious diseases.

[47]  I. Frieden,et al.  Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. , 2015, Journal of the American Academy of Dermatology.

[48]  Sung-Churl Lee,et al.  Early Additional Immune-Modulators for Mycoplasma pneumoniae Pneumonia in Children: An Observation Study , 2014, Infection & chemotherapy.

[49]  Maureen H Diaz,et al.  Investigations of Mycoplasma pneumoniae Infections in the United States: Trends in Molecular Typing and Macrolide Resistance from 2006 to 2013 , 2014, Journal of Clinical Microbiology.

[50]  Chin‐Yun Lee,et al.  Comparison of real-time polymerase chain reaction and serological tests for the confirmation of Mycoplasma pneumoniae infection in children with clinical diagnosis of atypical pneumonia. , 2014, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[51]  Deli Xin,et al.  Drug Resistance Mechanisms of Mycoplasma pneumoniae to Macrolide Antibiotics , 2014, BioMed research international.

[52]  Jae Hong Choi,et al.  Macrolide Resistance of Mycoplasma pneumoniae, South Korea, 2000–2011 , 2013, Emerging infectious diseases.

[53]  Ling Cao,et al.  Multiple-Locus Variable-Number Tandem-Repeat Analysis of Mycoplasma pneumoniae Clinical Specimens and Proposal for Amendment of MLVA Nomenclature , 2013, PloS one.

[54]  K. To,et al.  Comparison of Pyrosequencing, Sanger Sequencing, and Melting Curve Analysis for Detection of Low-Frequency Macrolide-Resistant Mycoplasma pneumoniae Quasispecies in Respiratory Specimens , 2013, Journal of Clinical Microbiology.

[55]  N. Miyashita,et al.  Transmission of macrolide-resistant Mycoplasma pneumoniae within a family , 2013, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[56]  Jae Hong Choi,et al.  Macrolide Resistance of Mycoplasma pneumoniae , 2013 .

[57]  S. Esposito,et al.  Clinical Relevance of Mycoplasma pneumoniae Macrolide Resistance in Children , 2012, Journal of Clinical Microbiology.

[58]  Kyung-Yil Lee,et al.  Mycoplasma pneumoniae pneumonia in children , 2012, Korean journal of pediatrics.

[59]  S. Pereyre,et al.  Mycoplasma pneumoniae: susceptibility and resistance to antibiotics. , 2011, Future microbiology.

[60]  H. Tsutsumi,et al.  Japanese Guidelines for the Management of Respiratory Infectious Diseases in Children 2007 with focus on pneumonia , 2011, Pediatrics international : official journal of the Japan Pediatric Society.

[61]  M. Morozumi,et al.  Macrolide-resistant Mycoplasma pneumoniae: characteristics of isolates and clinical aspects of community-acquired pneumonia , 2010, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[62]  M. Suyama,et al.  Transcriptome Complexity in a Genome-Reduced Bacterium , 2009, Science.

[63]  K. Sunakawa,et al.  A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma pneumoniae infections in pediatric patients , 2009, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[64]  Kyung-Yil Lee Pediatric respiratory infections by Mycoplasma pneumoniae , 2008, Expert review of anti-infective therapy.

[65]  P. Björkman,et al.  Polymerase chain reaction is superior to serology for the diagnosis of acute Mycoplasma pneumoniae infection and reveals a high rate of persistent infection , 2008, BMC Microbiology.

[66]  S. Pereyre,et al.  Reduced susceptibility to tetracyclines is associated in vitro with the presence of 16S rRNA mutations in Mycoplasma hominis and Mycoplasma pneumoniae. , 2008, The Journal of antimicrobial chemotherapy.

[67]  C. Lück,et al.  Sensitive Detection of Mycoplasma pneumoniae in Human Respiratory Tract Samples by Optimized Real-Time PCR Approach , 2007, Journal of Clinical Microbiology.

[68]  M. Nussinovitch,et al.  Absence of Tooth Staining With Doxycycline Treatment in Young Children , 2007, Clinical pediatrics.

[69]  M. Matsuoka,et al.  Clinical Evaluation of Macrolide-Resistant Mycoplasma pneumoniae , 2006, Antimicrobial Agents and Chemotherapy.

[70]  H. Goossens,et al.  Evaluation of 12 Commercial Tests and the Complement Fixation Test for Mycoplasma pneumoniae-Specific Immunoglobulin G (IgG) and IgM Antibodies, with PCR Used as the “Gold Standard” , 2005, Journal of Clinical Microbiology.

[71]  D. Gruson,et al.  In Vitro Development of Resistance to Six and Four Fluoroquinolones in Mycoplasma pneumoniae and Mycoplasma hominis, Respectively , 2005, Antimicrobial Agents and Chemotherapy.

[72]  A. Chang,et al.  Antibiotics for community acquired lower respiratory tract infections (LRTI) secondary to Mycoplasma pneumoniae in children. , 2005, The Cochrane database of systematic reviews.

[73]  H. Ohya,et al.  Characterization and Molecular Analysis of Macrolide-Resistant Mycoplasma pneumoniae Clinical Isolates Obtained in Japan , 2004, Antimicrobial Agents and Chemotherapy.

[74]  Ken B. Waites,et al.  Mycoplasma pneumoniae and Its Role as a Human Pathogen , 2004, Clinical Microbiology Reviews.

[75]  R. Herrmann,et al.  Preference, adaptation and survival of Mycoplasma pneumoniae subtypes in an animal model. , 2004, International journal of medical microbiology : IJMM.

[76]  S. Shott,et al.  Analysis of Eight Commercial Enzyme Immunoassay Tests for Detection of Antibodies to Mycoplasma pneumoniae in Human Serum , 2004, Clinical Diagnostic Laboratory Immunology.

[77]  R. Herrmann,et al.  Subtyping of Mycoplasma pneumoniae isolates based on extended genome sequencing and on expression profiles. , 2003, International journal of medical microbiology : IJMM.

[78]  K. Mcintosh Community-acquired pneumonia in children. , 2002, The New England journal of medicine.

[79]  Y. Arakawa,et al.  Characteristics of Macrolide‐Resistant Mycoplasma pneumoniae Strains Isolated from Patients and Induced with Erythromycin In Vitro , 2001, Microbiology and immunology.

[80]  J. Jensen,et al.  Molecular typing of Mycoplasma pneumoniae strains by PCR-based methods and pulsed-field gel electrophoresis. Application to French and Danish isolates , 2000, Epidemiology and Infection.

[81]  Y. Naot,et al.  Molecular Biology and Pathogenicity of Mycoplasmas , 1998, Microbiology and Molecular Biology Reviews.

[82]  T. Pallasch Macrolide antibiotics. , 1997, Dentistry today.

[83]  P. Hu,et al.  Transition mutations in the 23S rRNA of erythromycin-resistant isolates of Mycoplasma pneumoniae , 1995, Antimicrobial agents and chemotherapy.

[84]  J. Horton,et al.  Restriction fragment length polymorphism in the cytadhesin P1 gene of human clinical isolates of Mycoplasma pneumoniae , 1990, Infection and immunity.

[85]  R. Khakoo,et al.  Mycoplasma pneumoniae infections. , 1981, The West Virginia medical journal.

[86]  R. Chanock,et al.  Growth on artificial medium of an agent associated with atypical pneumonia and its identification as a PPLO. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[87]  R. Chanock,et al.  Serologic evidence of infection with Eaton agent in lower respiratory illness in childhood. , 1960, The New England journal of medicine.