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Mycoplasma Infections: Differential Diagnoses & Workup

Author: Ken B Waites, MD, Director of Clinical Microbiology, Professor, Department of Pathology, Division of Laboratory Medicine, University of Alabama at Birmingham
Contributor Information and Disclosures

Updated: Nov 17, 2009

Differential Diagnoses

Other Problems to Be Considered

Respiratory syncytial virus
Coxiella burnetii
Chlamydia pneumoniae
S pneumoniae
Legionella species
Mycobacterium species
Other miscellaneous bacterial species
Histoplasma capsulatum

Workup

Laboratory Studies

Consider the possibility of infection with M pneumoniae in patients of any age who present with respiratory tract infections. Laboratory investigation should focus on both the clinical illness (eg, tracheobronchitis vs pneumonia) and the many possible infectious etiologies that can cause clinically similar manifestations. The extent of laboratory investigation also should reflect the severity of the illness and whether the illness warrants hospitalization.

In as many as half of all cases of community-acquired pneumonias, the microbiological etiology is never determined, despite appropriate laboratory testing. The typical mild illness caused by M pneumoniae in otherwise healthy persons may not warrant a comprehensive microbiological investigation because empiric treatment with oral antimicrobials can cover M pneumoniae and most other bacterial agents that produce similar illnesses.

• Laboratory analysis
  • Twenty-five percent of patients develop leukocytosis; the rest have leukocyte counts within the reference range.
  • Thirty percent of patients have an elevated erythrocyte sedimentation rate.
  • Cellular response of sputum is mononuclear, with no bacteria visible with Gram staining.
  • About 75% of patients have a cold agglutinin titer of at least 1:32 by the second week of illness, disappearing by 6-8 weeks. This is not a specific test for M pneumoniae infection but the greater the cold agglutinin titer is (>1:64) in a patient with CAP, the more likely the cold agglutinins are due to M pneumoniae. No specific abnormalities of hepatic or renal function are likely to occur.
  • To confirm mycoplasmal respiratory tract infection, culture, molecular-based tests, and serological tests are necessary.
• Culture
  • Respiratory tract specimens suitable for culture include throat swabs, sputum, tracheal aspirates, bronchial lavage fluid, pleural fluid, or lung biopsy tissue, depending on the patient's clinical condition.
  • Mycoplasmal organisms have fastidious growth requirements and are often difficult to grow in a cell-free medium. Take care during specimen collection to inoculate into a suitable transport medium (eg, SP4 broth), at the bedside whenever possible, and to not allow desiccation. Clinicians advise freezing at -70°C if specimens cannot be transported to the diagnostic laboratory immediately after collection.
  • Growth in culture is slow, requiring 3 weeks in some cases, and the culture is not extremely sensitive for detecting M pneumoniae infection. The culture medium is often unavailable except from specialized reference laboratories. If culture is attempted, alternative procedures including serology and molecular-based nucleic acid amplification tests should also be performed.⁷
• Serological testing
  • Physicians use serology most frequently to confirm M pneumoniae infection.
  • Many clinicians prefer enzyme-linked immunosorbent assays to the older, less sensitive complement fixation assays and nonspecific cold agglutinin titers. These types of tests are widely available through commercial reference laboratories.
  • Because primary infection does not guarantee protective immunity against future infections and residual immunoglobulin G (IgG) may remain from earlier encounters with the organism, experts have launched a great impetus to develop sensitive and specific tests that can differentiate between acute and remote infection.
  • Definitive diagnosis requires seroconversion documented by paired specimens obtained 2-4 weeks apart. Although researchers purport that single-titer immunoglobulin M (IgM) or immunoglobulin A (IgA) assays reveal current infection, data regarding how long IgM persists after acute infection are not clear, and as many as 50% of adults may not mount a detectable IgM response. Conversely, some children may not mount a measurable IgG response, and the IgG response in adults may be delayed for several days. Therefore, relying on a single serological test can be clinically misleading, and experts recommend basing diagnosis of acute infection on seroconversion measured simultaneously in assays for both IgM and IgG. Use of serology for diagnosis of mycoplasmal infection is valid only if the patient has a satisfactory capacity of the humoral immune system to mount an antibody response.
• Rapid diagnostic enzyme-linked immunosorbent assays
  • One of the most significant advances in recent years for the diagnosis of M pneumoniae respiratory tract infections is the development of qualitative, rapid, single-specimen, membrane-based enzyme-linked immunosorbent assays that are readily adaptable to the primary care physician's office laboratory.⁸
  • The Remel IgG/IgM Antibody Test System (Remel Laboratories; Lenexa, Kan) measures both IgG and IgM simultaneously.
  • The Meridian ImmunoCard (Meridian Laboratories; Cincinnati, Ohio) measures only IgM.
  • Physicians can perform both tests without special expertise or equipment, and they can interpret the results in approximately 10 minutes, eliminating the need for collection of paired sera for later antibody measurement.
  • Both tests have a moderate complexity classification under the Clinical Laboratory Improvement Act (CLIA), allowing many physicians to offer serologic assays for M pneumoniae antibodies as a point-of-care test so that it can be used to direct patient management.
  • Such single-specimen assays have limitations as described above; perhaps the most practical use for the IgM ImmunoCard is when an acute infection with M pneumoniae is suspected in children and young adults.
• Molecular analysis
  • Researchers have developed molecular-based systems for detection of M pneumoniae using polymerase chain reaction (PCR); however, only limited information describing the application of this methodology in a clinical setting is available. Some reference laboratories offer PCR assays for detection of current mycoplasmal infection.
  • Carriage of mycoplasmas in the upper respiratory tract for variable periods following prior infection may confound the interpretation of a single positive polymerase chain reaction assay result. Furthermore, a PCR assay may reveal very small numbers of organisms that may not be of etiologic significance.
  • A specific threshold of quantity of mycoplasmas in the respiratory tract that can differentiate colonization from infection has not been established, so a highly sensitive detection method such as PCR performed in a nonquantitative manner may overestimate the clinical importance of M pneumoniae as a pathogen since it often cocirculates with other bacterial and viral respiratory pathogens. For these reasons, molecular-based assays should be accompanied by serological assays for maximum diagnostic accuracy unless testing a normally sterile body fluid in which the presence of any number of mycoplasmas would be considered evidence of disease.²

Imaging Studies

• Abnormalities on chest radiographs often appear more severe than predicted based on the clinical condition of the patient.
• Lobar consolidation is unusual.
• Diffuse or interstitial infiltrates that involve the lower lobes are the most common radiographic abnormalities.
• Small pleural effusions may develop in approximately 20% of cases.
• Lung involvement tends to be unilateral but can be bilateral.

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