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.
Diagnosis
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)
- Negative result does not rule out infection
- 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
- Influenza
- Parainfluenza virus 1, 2, 3
- Legionella pneumophila
- C. pneumoniae or psittaci
- Respiratory syncytial virus
- Bordetella pertussis
- Adenovirus
- Metapneumovirus
- Hantavirus
Background
Epidemiology
- 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
Organism
- 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
- Hemolysis/hemolytic anemia
- Skin rashes
- Erythema nodosum or erythema multiforme
- Thrombocytopenia
- Guillain-Barré syndrome
- Syndromes caused by spread of organism
ARUP Laboratory Tests
Detect M. pneumoniae bacteria
Qualitative Polymerase Chain Reaction
Aid in diagnosis of M. pneumoniae in patient with persistent pneumonia that is outside of the expected acute phase
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Hemagglutination
Panel that combines M. pneumoniae IgG and IgM antibodies is preferred
Low IgM antibody levels may persist more than 12 months postinfection
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Panel that combines M. pneumoniae IgG and IgM antibodies is preferred
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Preferred test to confirm respiratory syncytial virus (RSV) or influenza in general inpatients and RSV in adults
Qualitative Reverse Transcription Polymerase Chain Reaction
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)
Qualitative Polymerase Chain Reaction
Detect C. pneumoniae in bronchoalveolar lavage (BAL), nasal wash, nasopharyngeal swab, or pleural fluid
Qualitative Polymerase Chain Reaction
Differentiate between Chlamydophila species (C. psittaci, C. 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
Semi-Quantitative Indirect Fluorescent Antibody
Provide retrospective evidence of suspected L. pneumophila infection
Qualitative Enzyme-Linked Immunosorbent Assay
Medical Experts
Couturier

Hillyard

References
18754792
Atkinson TP, Balish MF, Waites KB. Epidemiology, clinical manifestations, pathogenesis and laboratory detection of Mycoplasma pneumoniae infections. FEMS Microbiol Rev. 2008;32(6):956-973.
A Manual of Laboratory and Diagnostic Tests - Overview of Immunodiagnostic Studies
Fischbach F, Dunning M. Chapter 8: overview of immunodiagnostic studies. A Manual of Laboratory and Diagnostic Tests. 8th ed. Lippincott Williams & Wilkins; 2009.
20526788
Loens K, Goossens H, Ieven M. Acute respiratory infection due to Mycoplasma pneumoniae: current status of diagnostic methods. Eur J Clin Microbiol Infect Dis. 2010;29(9):1055-1069.
19331586
Thurman KA, Walter ND, Schwartz SB, et al. Comparison of laboratory diagnostic procedures for detection of Mycoplasma pneumoniae in community outbreaks. Clin Infect Dis. 2009;48(9):1244-1249.
22125034
Waites KB. What's new in diagnostic testing and treatment approaches for Mycoplasma pneumoniae infections in children? Adv Exp Med Biol. 2011;719:47-57.
21985809
Zhang L, Zong ZY, Bin Liu Y, et al. PCR versus serology for diagnosing Mycoplasma pneumoniae infection: a systematic review & meta-analysis. Indian J Med Res. 2011;134:270-280.