Condition

Mycoplasma Pulmonary Infections

Editors: Julio A. Ramirez MD; David M. Dobrzynski Jr. MD; Zbigniew Fedorowicz PhD, MSc, DPH, BDS, LDSRCS; Paritosh Prasad MD

American College of PhysiciansProduced in collaboration with American College of Physicians
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Background Information

Description

  • Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, and it is typically associated with mild disease with a persistent cough.
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  • Severe pneumonia, exacerbation of underlying pulmonary conditions, and extrapulmonary complications may occur in some patients.
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  • For information on the role of Ureaplasma in pulmonary disease in infants, see Bronchopulmonary Dysplasia (BPD).

Also Called

  • Walking pneumonia
  • Atypical pneumonia

Epidemiology

Incidence/Prevalence

Pneumonia
  • The incidence and prevalence of Mycoplasma pneumoniae infections is likely underestimated due to:
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    • Its often asymptomatic or mild presentation
    • Lack of accurate diagnostic tests
    • Infections that mimic or coexist with M. Pneumoniae
  • M. pneumoniae is reported to cause 2%-40% of community-acquired pneumonia.
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    • 4%-8% of sporadic infection is reported to occur in adults
    • 20%-70% is reported to occur during epidemics
  • In the United States:
    • An estimated 2 million cases of Mycoplasma pneumoniae infection occur annually, but because there is no national reporting or surveillance, the actual number is likely higher (CDC 2024 Oct 18).
    • In 2024, pulmonary infections caused by Mycoplasma pneumoniae have been increasing in the United States, especially among young children (CDC 2024 Oct 17).
    • About 100,000 hospitalizations per year in adults in the United States are reportedly due to M. pneumoniae.
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  • In China:
    • In September 2023, a high incidence of Mycoplasma pneumoniae infections in children were reported in several regions across China. Macrolide-resistantM. pneumoniae was reported to predominantly drive this outbreak. The real-time polymerase chain reaction assays of patients tested revealed the following positive detection rates for M. pneumoniae:
      • 25.4% in the outpatient setting
      • 48.4% in the inpatient setting
      • Up to 61.6% in patients with respiratory conditions
      • Reference - World J Pediatr 2024 Jan;20(1):1
    • STUDY SUMMARY
      M. pneumoniae detected in 14.4% of patients with respiratory tract infections in North China between 2011 and 2016
      COHORT STUDY: BMC Infect Dis 2018 Jul 17;18(1):335

    • STUDY SUMMARY
      M. pneumoniae detected in 3.7% of infants hospitalized with lower respiratory tract infections in China between 2012 and 2013
      COHORT STUDY: Respir Med 2015 Jun;109(6):751

Macrolide-Resistance
  • Macrolide-resistance was first reported in Japan in 2000, and has spread worldwide.
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  • Reported rates of macrolide-resistant isolates vary by geographic area:
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    • Almost 90% in Japan and China
    • Almost 30% in Italy and Israel
    • About 10% in Canada and the United States
    • < 1% in Slovenia and the Netherlands
  • STUDY SUMMARY
    in M. pneumoniae-positive specimens collected from children and adults with community-acquired infection from 2018 to 2020, macrolide resistance reported in 34% in Asia, 10% in Europe, and 9% in North America
    SYSTEMATIC REVIEW: J Antimicrob Chemother 2022 Aug 25;77(9):2353

  • STUDY SUMMARY
    macrolide resistance reported in 29% of Mycoplasma pneumoniae specimens from nonoutbreak infections and 7% of outbreak-associated infections in United States
    COHORT STUDY: J Clin Microbiol 2015 Jan;53(1):124

  • STUDY SUMMARY
    all M. pneumoniae isolates from patients with community-acquired pneumonia in Yantai, China, between 2015 and 2016 were macrolide resistant
    COHORT STUDY: Colomb Med (Cali) 2018 Jun 30;49(2):160

  • STUDY SUMMARY
    14.5% of M. pneumoniae isolates from children with community-acquired pneumonia in Japan between 2002 and 2006 were macrolide resistant
    COHORT STUDY: Antimicrob Agents Chemother 2008 Jan;52(1):348

Risk Factors

  • Risk of infection is highest in patients aged 5-20 years.
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  • Hypogammaglobulinemia is associated with an increased risk of Mycoplasma infections.
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  • Sickle cell disease may be associated with increased disease severity.
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  • The majority of outbreaks occur in crowded environments, including:
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    • Military barracks
    • Schools and universities
    • Hospitals
    • Long-term care facilities
  • See also Community-acquired Pneumonia in Adults and Community-Acquired Pneumonia in Children.

Associated Conditions

  • Mycoplasma pneumoniae pneumonia often occurs in HIV-infected populations.
    • This is reported to cause 11%-21% of pneumonia in HIV infected individuals.
    • Children with HIV and M. Pneumoniae may have CD4 cell counts < 20 cells/mcL.
    • Antibody detection of M. Pneumoniae in patients with HIV is difficult due to an impaired immune response.
    • Immunosuppressed HIV-infected patients may never develop a detectable antibody response.
    • Reference - Pneumonia (Nathan) 2017;9:12

Etiology and Pathogenesis

Pathogen

  • Mycoplasma pneumoniae is 1-2 micrometers long and 0.1-0.2 micrometers wide, with cell volume < 5% of typical bacillus.
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    • On agar plates, colonies resemble "fried eggs" with diameter typically ≤ 100 micrometers.
    • It lacks a cell wall, and is supported by sterols in a triple-layer cell membrane. Therefore, it is resistant to antimicrobials with activity against cell walls (such as beta-lactams) and Gram stain is ineffective.
    • It cannot be seen on light microscopy.
    • It is not found freely living in nature, and is predominantly considered a mucosal pathogen, existing parasitically on the epithelial surface of the host.
  • 2 genetic groups of mycoplasma have been identified and may determine the emergence of epidemics.
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    • Subtype 1 and subtype 2 are differentiated based on difference in the P1 protein gene (repetitive elements of RepMP2/3 and RepMP4).
    • 1 subtype may intermittently emerge following induced transient herd immunity produced by the initial genetic subtype.

Transmission

  • Mycoplasma infections occur sporadically throughout the year, but may also occur as community outbreaks.
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  • Person-to-person transmission occurs through airborne droplets.
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  • Transmission typically occurs through close contact (mycoplasma are highly susceptible to drying out and becoming noninfective due to a lack of cell wall).
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  • The incubation period is typically 1-4 weeks.
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Pathogenesis

  • Disease manifestations may arise from:
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    • Direct infection with mycoplasma at a site of inflammation and activation of local cytokines, including cold agglutinins to I-antigen of red blood cells
    • Indirect autoimmune and vascular complications
  • Attachment organelle play key role in adherence to host epithelial cells.
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    • There is a specialized cellular structure that allows for cytoadherence.
    • The cytoskeletal proteins within the attachment organelle facilitate adherence and motility.
  • Once Mycoplasma pneumoniae binds to host tissue, an array of events leads to pathogenesis.
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    • The metabolism of glycerol produces hydrogen peroxide and superoxide which injures epithelial cells and their cilia.
      • Denaturation of hemoglobin, peroxidation of lipids, and cell lysis can occur.
      • Oxidative stress in respiratory epithelium may result in damage to cilia.
    • Lipoproteins/lipopeptides induce Toll-like receptors TLR1, TLR2, TLR4, and TLR6, leading to:
      • Amplified production of chemokines promoting lymphocyte and neutrophil trafficking
      • Lung inflammation
    • Community-acquired respiratory distress syndrome (CARDS) toxin may lead to inflammation and airway destruction as the following can occur:
      • Mycoplasma pneumoniae binds to human surfactant protein A and annexin A2 on airway epithelial cells, and after internalization leads to a range of events
      • Vacuolation and ciliostasis of host cells have been reported
      • Can stimulate expression of Th-2 cytokines and Th-2 chemokines causing eosinophilia, accumulation of T and B cells, and mucous metaplasia
      • Produces free radicals causing further cytotoxicity

Immune Response

  • Immunity lasts about 4 years (range 2-10 years).
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  • Repeated infections are possible in the same patient.
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