Mycoplasma pneumoniae Infection

Mycoplasmas, the smallest self-replicating organisms, include M. pneumoniae (pneumonia), M. genitalium, and Ureaplasma urealyticum (urethritis). M. pneumoniae is a common cause of community-acquired pneumonia.


Indications for Testing

  • Mild illness consisting of upper or lower respiratory illness with gradual onset of
    • Malaise
    • Fever
    • Headache
    • Sore throat
    • Persistent cough
    • Atypical pneumonia appearance on chest x-ray (patchy unilateral or diffuse bilateral infiltrates)
  • Appearance of extrapulmonary symptoms in addition to severe pneumonia – usually prompts testing
    • Rash, including Stevens-Johnson syndrome
    • Hemolysis, secondary to IgM cold agglutinins
    • Cardiac involvement including conduction disturbances, arrhythmias, congestive heart failure, and chest pain
    • Central nervous system (CNS) involvement
    • Gastrointestinal manifestations, eg, nausea, vomiting, and diarrhea
    • Joint pain
  • If indications are not present, testing for Mycoplasma pneumoniae is not indicated as this is usually a mild, self-limited disease that responds to macrolide antibiotics

Laboratory Testing

  • Polymerase chain reaction (PCR) 
    • Rapid test to identify M. pneumoniae
    • Increased sensitivity if sputum is tested and infection is in early stage (first 21 days after onset)
    • Probably most sensitive test to use, especially in adults who may not mount significant IgM levels early in infection
  • IgG, IgM by enzyme-linked immunosorbent assay (ELISA), complement fixation
    • Usually requires acute and convalescent samples
    • Not effective in early diagnosis
  • Cold agglutinins – especially if hemolysis is present or suspected
    • Negative result does not rule out infection
      • 30-50% of patients with M. pneumoniae will develop cold agglutinins (Fischbach, 2009)
  • Culture
    • Inadequate for acute diagnosis
    • Not recommended; bacteria are relatively fastidious and require a long incubation (up to 4 weeks)
  • Consider concurrent testing for Chlamydia pneumoniae, urinary antigen detection for Legionella, viral studies (eg, PCR panel) for respiratory viruses

Imaging Studies

Chest radiography – patchy unilateral infiltrates or diffuse bilateral interstitial process

Differential Diagnosis



  • Prevalence
    • Responsible for 15-20% of all community-acquired pneumonia; higher rates among school children and people in closed populations (military recruits)
    • 2-5% of patients require hospitalization as compared with 15-20% hospitalization rates for other causes of pneumonia
  • Transmission
    • Respiratory droplet
    • Most common in U.S. during late summer to early fall


  • M. pneumoniae
    • Flask-shaped bacteria with no true cell wall and a very small genome (816 kilobase pairs)
    • Facultative intracellular parasite
    • Cultivation in vitro is difficult
      • Fastidious nature
      • Dependence on externally supplied growth factors (by host organism or in culture medium)
      • Limited metabolic capacity inherent in small genome

Clinical Presentation

  • Most infections are mild and often indistinguishable from other viral and atypical bacterial pathogens
  • Initial symptoms
    • Malaise, myalgias, sore throat, headache (retro-orbital), ear pain, and fever
  • Advanced infection
    • Dry, nonproductive cough occurs 3-5 days after onset of initial nonspecific symptoms
    • Cough may produce mucopurulent sputum later in illness
    • May be accompanied by chills, chest pain, shortness of breath, nausea, vomiting, diarrhea
    • Patients usually seek medical attention after 5-7 days – cough may become paroxysmal and nocturnal
    • Cough may persist several weeks following resolution of constitutional symptoms
    • Pleural effusions more common in severe disease
  • Extrapulmonary manifestations of M. pneumoniae infection
    • Syndromes caused by spread of organism
      • Bullous hemorrhagic otitis
      • Arthritis
      • Acute respiratory distress syndrome
      • Myocarditis with conduction disturbances and chest pain
      • Encephalitis/meningitis
      • Sinusitis
    • Immunologically mediated syndromes

ARUP Laboratory Tests

Detect M. pneumoniae bacteria

Aid in diagnosis of M. pneumoniae in patient with persistent pneumonia that is outside of the expected acute phase

Related Tests

Panel that combines M. pneumoniae IgG and IgM antibodies is preferred

Low IgM antibody levels may persist more than 12 months postinfection

Panel that combines M. pneumoniae IgG and IgM antibodies is preferred 

Preferred test to confirm respiratory syncytial virus (RSV) or influenza in general inpatients and RSV in adults

Preferred test for evaluating severely immunocompromised (eg, bone marrow transplant [BMT]) or critically ill (ICU) patients with respiratory symptoms

Detect influenza (A H1, A H3, A 2009 H1N1, B), RSV (A, B), parainfluenza (1, 2, 3), human metapneumovirus (hMPV), human rhinovirus, and adenovirus (B/E, C)

Detect C. pneumoniae in bronchoalveolar lavage (BAL), nasal wash, nasopharyngeal swab, or pleural fluid

Differentiate between Chlamydophila species (C. psittaciC. pneumoniae)

Differentiate early IgM response to infection from persistent low-level titer

Because of cross-reactivity, a C. pneumoniae-specific reaction will exhibit titers 2-fold or greater than C. trachomatis or C. psittaci serology

Limited value in diagnosis of most oculogenital (eg, eyes, genitalia) chlamydial infections

Provide retrospective evidence of suspected L. pneumophila infection


Additional Resources

Medical Experts



Marc Roger Couturier, PhD, D(ABMM)
Professor of Pathology (Clinical), University of Utah
Medical Director, Emerging Public Health Crises, Parasitology/Fecal Testing, and Infectious Disease Antigen Testing, ARUP Laboratories


David R. Hillyard, MD
Adjunct Associate Professor of Pathology, University of Utah
Medical Director, Molecular Infectious Diseases, ARUP Laboratories