AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mycoplasma species are the smallest free-living organisms. These organisms are unique among prokaryotes in that they lack a cell wall, a feature largely responsible for their biologic properties such as their lack of a reaction to Gram stain and their lack of susceptibility to many commonly prescribed antimicrobial agents, including beta-lactams. Mycoplasmal organisms are usually associated with mucosal surfaces, residing extracellularly in the respiratory and urogenital tracts. They rarely penetrate the submucosa, except in the case of immunosuppression or instrumentation, when they may invade the bloodstream and disseminate to different organs and tissues throughout the body.

Although scientists have isolated at least 17 species of Mycoplasma from humans, 4 types of organisms are responsible for most clinically significant infections that may come to the attention of practicing physicians. These species are Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma species. The focus of this article is infections caused by M pneumoniae; articles on Ureaplasma infections (eg, Ureaplasma Infection) and genital mycoplasmal infections contain discussions of infections caused by other mycoplasmal species.

Pathophysiology

M pneumoniae is perhaps best known as the cause of walking or atypical pneumonia, but the most frequent clinical syndrome caused by this organism actually is tracheobronchitis or bronchiolitis, often accompanied by upper respiratory tract manifestations. Pneumonia develops in only 5-10% of persons who are infected. Acute pharyngitis and myringitis are less common.

After inhalation of respiratory aerosols, the organism attaches to host cells in the respiratory tract. The P1 adhesin and other accessory proteins mediate attachment, followed by induction of ciliostasis, local inflammation that consists primarily of perivascular and peribronchial infiltration of mononuclear leukocytes, and tissue destruction that may be mediated by liberation of peroxides. The organism also has the ability to exist intracellularly.¹ Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma.²

Spread of infection throughout households is common, although person-to-person transmission is slower than for many other common bacterial respiratory tract infections; close contact appears necessary. Generally, the incubation period is 2-3 weeks. The organism may persist in the respiratory tract for several months, and sometimes for years in patients who are immunosuppressed, after initial infection.³

For additional information on pneumonia, see Medscape's Pneumonia Resource Center.

Frequency

United States

Researchers estimate that more than 2 million cases of M pneumoniae infections occur annually. M pneumoniae causes approximately 20% of community-acquired pneumonias that require hospitalization and probably an even greater proportion of those that do not require hospitalization. M pneumoniae may exist endemically in large urban areas. Epidemics occur every 3-7 years, with the incidence varying considerably from year to year. Disease tends to not be seasonal, except for a slight increase in late summer and early fall.¹

International

M pneumoniae infections occur both endemically and in cyclic epidemics in Japan and several European countries, similar to what occurs in the United States. Less information is available for tropical or polar countries; however, based on seroprevalence studies, the disease also occurs in these regions, suggesting that climate and geography are not important determinants in the epidemiology of M pneumoniae infections.¹

Mortality/Morbidity

• As the term walking pneumonia implies, the great majority of M pneumoniae respiratory tract infections are mild and self-limited, although administration of antimicrobials hastens clinical resolution. Hospitalization is sometimes necessary, but recovery is almost always complete and without sequelae. Recent studies have indicated that M pneumoniae is second only to Streptococcus pneumoniae as a cause of bacterial pneumonia that requires hospitalization in elderly adults.⁴ Subclinical infections may occur in 20% of adults infected with M pneumoniae, suggesting that some degree of immunity may contribute to the failure of clinical symptoms in some instances.
• Recent evidence suggests that M pneumoniae disease is sometimes much more severe than appreciated, even in otherwise healthy children and adults.² Severe disease is more common in persons with underlying disease or immunosuppression. Children with sickle cell disease and functional asplenia may be at greater risk for severe respiratory tract disease due to M pneumoniae. While reports describe fatal cases of mycoplasmal pneumonia, the overall mortality rate is extremely low, probably less than 0.1%.

Race

• No racial predilection is apparent.

Sex

• Available studies indicate no sexual predilection for M pneumoniae disease.

Age

• M pneumoniae has long been associated with pneumonias in children aged 5-9 years, adolescents, and young adults. Infection is particularly common among college students and military recruits who are likely to live together in close proximity. M pneumoniae may be the most common agent causing bacterial pneumonia in such populations.
• In recent years, M pneumoniae infection has been common in persons older than 65 years, accounting for as much as 15% of community-acquired pneumonia cases in persons in this age group.
• The common misconception that M pneumoniae disease is rare among very young populations and among older adults has led to physician failure to consider the organism in the differential diagnoses of respiratory tract infections in persons in these age groups. Physicians should always consider M pneumoniae as a cause of pneumonia in persons of all ages, including children younger than 5 years. Although M pneumoniae disease in infants is somewhat uncommon, when it is present, it can be severe.⁵

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Typical symptoms can develop and persist over weeks to months and include flulike manifestations.

• Symptoms
• • Generalized aches and pains
  • Fever (usually £102°F)
  • Cough - Usually nonproductive
  • Sore throat (nonexudative pharyngitis)
  • Headache/myalgias
  • Chills but not rigors
  • Nasal congestion with coryza
  • Earache
  • General malaise
• In very young children, upper respiratory tract manifestations may predominate, whereas in older children and adults, lower respiratory tract symptoms are more likely.

Physical

Physical findings can be quite variable. Patients typically do not appear toxic or severely ill, but some abnormalities may be apparent in a significant proportion of cases.

• Physical findings
• • Oropharyngeal inflammation
  • Cervical adenopathy - Usually absent
  • Erythematous tympanic membranes
  • Conjunctivitis
  • Maculopapular or urticarial rash
• Chest auscultation in patients with pneumonia may demonstrate localized rhonchi and scattered moist rales, generally involving multiple lobes of the lung and sometimes accompanied by wheezes, with no signs of consolidation, egophony, or bronchial breathing.
• In many persons, chest auscultative and percussive abnormalities are minimal to absent.
• Extrapulmonary manifestations may occur in a minority of persons (see Complications).²

Causes

This is a bacterial infection caused by M pneumoniae.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

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

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab 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.⁵
• 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.⁶
  • 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 the polymerase chain reaction; however, only limited information describing the application of this methodology in a clinical setting is available, and no assays of this type are commercially available. Some reference laboratories offer these types of tests for patient care purposes using reagents developed internally.
  • 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 polymerase chain reaction 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 the polymerase chain reaction 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.¹

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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Ambulatory care versus hospitalization
• • The choice of outpatient management versus hospitalization for persons with community-acquired pneumonia depends on the clinical syndrome and not the organism, largely because the microbiologic diagnosis is often unavailable when the physician must make these decisions.
  • Professional organizations of physicians and managed care organizations have developed management algorithms that include decision trees for diagnostic studies and management, including specifications of antimicrobial agents to be used. These guidelines vary somewhat, but, in general, the decision to hospitalize a patient depends on an assessment of the following:
  • • The person's ability to tolerate and comply with oral medication
    • Whether the patient appears hypoxic or toxic to the extent that the physician suspects a bacteremic pneumonia
    • Whether the person is immunosuppressed
  • Relatively few patients with M pneumoniae pneumonia require hospitalization based on these criteria.
• Antimicrobials
• • Experts formerly believed that mycoplasmal respiratory tract infections were entirely self-limited and that antimicrobial treatment was not indicated.
  • Appropriate antimicrobial therapy shortens the symptomatic period and hastens radiological resolution of pneumonia and recovery, even though patients may shed organisms for several weeks.
  • When treating community-acquired pneumonia, physicians usually must provide empiric coverage for several different bacterial agents that may be responsible because the microbiologic diagnosis is seldom available at the initiation of treatment. Fortunately, many of the drugs of choice for treating M pneumoniae provide broad-spectrum coverage for other organisms.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

M pneumoniae remains predictably susceptible to macrolides and tetracyclines; therefore, in vitro susceptibility testing to guide therapy is not indicated.

Oral erythromycin has long been the DOC for mycoplasmal respiratory tract infections. Tetracycline and its analogues are also active. Clindamycin is effective in vitro, but limited reports suggest it may not be active in vivo and thus is not considered a first-line treatment. Several of the newer fluoroquinolones exhibit bactericidal antimycoplasmal activity but are generally less potent in vitro than macrolides against M pneumoniae. Their advantage lies in the fact that they are active against all classes of bacteria that produce clinically similar respiratory tract infections, including macrolide-resistant Streptococcus pneumoniae. As would be predicted by the lack of a cell wall, none of the beta-lactams is effective in vitro or in vivo against M pneumoniae, and neither are the sulfonamides or trimethoprim.¹

Mycoplasma species are slow-growing organisms that have the capacity to reside intracellularly; thus, respiratory tract infections are expected to respond better to longer treatment courses than might be offered for other types of infections. Although physicians typically prescribe most treatment regimens (ie, both oral and parenteral) for 7-10 days, a 14- to 21-day course of oral therapy with most agents is also appropriate. A 5-day course of oral azithromycin is approved for the treatment of community-acquired M pneumoniae pneumonia. Clinical data indicate that this duration of treatment is of comparable efficacy to a 10-day course of erythromycin. Other newer drugs including telithromycin and various fluoroquinolones have been approved for the treatment of mycoplasmal respiratory infections with shorter courses because of their favorable pharmacokinetics.

In addition to the administration of antimicrobials for the management of M pneumoniae infections, other measures (eg, cough suppressants, antipyretics, analgesics) should be administered as needed to relieve headaches and other systemic symptoms. Because extrapulmonary manifestations are often diagnosed late in the course of disease, the benefit of early treatment is unknown.

Clinically significant acquired resistance to antimicrobials in M pneumoniae is believed to be uncommon, but no organized surveillance occurs in North America. Recent emergence of macrolide resistance in Japan that was associated with a greater morbidity in persons with mycoplasmal pneumonias is worrisome and serves as a reminder to clinicians to monitor patient outcomes and to consider using alternative antimicrobial agents if an initial treatment is unsuccessful.⁷

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• With appropriate treatment, uncomplicated episodes of M pneumoniae infection can be expected to resolve clinically within 7-10 days after onset.
• Additional laboratory tests or radiographs are not usually necessary unless the illness does not respond to therapy, which would raise questions about the accuracy of the microbiological diagnosis.
• The presence of extrapulmonary manifestations may warrant further workup and follow-up, depending on their nature and severity.
• Improvement of pneumonia on chest radiographs may lag behind clinical improvement.

Deterrence/Prevention

• Antimicrobial prophylaxis
• • As with other bacterial infections, researchers have studied the value of antimicrobial prophylaxis for those in contact with persons with M pneumoniae infection.
  • Klausner et al (1998) reported that the administration of oral azithromycin plus standard epidemic control measures significantly reduced secondary attack rates following an outbreak of M pneumoniae pneumonia in a long-term care facility for mentally and developmentally disabled persons.⁸
  • Previous studies using tetracyclines also demonstrated the efficacy of chemoprophylaxis in reducing transmission of M pneumoniae pneumonia.
• Vaccines
• • Researchers have studied vaccines for many years, but they have not produced a vaccine for general use.
  • The fact that natural infection does not confer complete protective immunity against future infections makes this approach less promising.
• Because of the endemicity of infection with M pneumoniae in susceptible populations, isolating patients is seldom practical and generally is not recommended.

Complications

• Extrapulmonary complications
• • Extrapulmonary complications may occur simultaneously with the onset of respiratory manifestations or as long as several days later. These complications may predominate to the extent that physicians may overlook a primary respiratory tract infection. Less than 10% of cases of M pneumoniae infections are associated with nonrespiratory illnesses, with the exception of various skin rashes, nausea, vomiting, and diarrhea, which may occur more often.⁶
  • When extrapulmonary manifestations occur, however, they clearly can complicate the diagnosis and the recovery; they also make hospitalization more likely. Thus, a careful history and physical examination are essential, and follow-up is indicated.
  • Researchers believe that an autoimmune response plays a role in some extrapulmonary complications, but, because M pneumoniae has been isolated directly from cerebrospinal, pericardial, and synovial fluids and from other extrapulmonary sites, always consider direct invasion by this organism.
  • Extrapulmonary manifestations may include the following:
  • • Meningoencephalitis
    • Ascending (ie, Guillain-Barré) paralysis
    • Transverse myelitis
    • Myopericarditis
    • Cardiac arrhythmia
    • Raynaud phenomenon
    • Hemolytic anemia
    • Disseminated intravascular coagulation
    • Renal failure
    • Arthritis
    • Erythema multiforme (ie, Stevens-Johnson syndrome)
    • Erythema nodosum
    • Urticaria
    • Ulcerative stomatitis
    • Nausea
    • Vomiting
    • Diarrhea

Prognosis

• Most persons who are free of underlying conditions that may adversely affect the outcome of a respiratory tract infection can expect an excellent prognosis and a full return of pulmonary function.
• For the minority of patients who have severe disease, diminished lung function may persist for weeks to months.
• For the few persons who experience disseminated extrapulmonary symptoms, particularly neurologic manifestations, recovery can require weeks to months. While most recover fully and uneventfully, some persons with neurologic manifestations may experience long-term paralysis and reports describe cases of permanent neurologic deficits.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• No medicolegal pitfalls are described.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev. Oct 2004;17(4):697-728, table of contents. [Medline].
2. Talkington DF, Waites KB, Schwartz S, Besser RE. Emerging from obscurity: Understanding pulmonary and extrapulmonary syndromes, pathogenesis, and epidemiology of human Mycoplasma pneumoniae infections. In: Scheld WM, Craig WA, Hughes JM, eds. Emerging infections. Vol 5. Washington, DC: ASM Press; 2001:57-84.
3. Foy HM. Infections caused by Mycoplasma pneumoniae and possible carrier state in different populations of patients. Clin Infect Dis. Aug 1993;17 Suppl 1:S37-46. [Medline].
4. Marston BJ, Plouffe JF, File TM Jr, et al. Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group. Arch Intern Med. Aug 11-25 1997;157(15):1709-18. [Medline].
5. Waites KB. New concepts of Mycoplasma pneumoniae infections in children. Pediatr Pulmonol. Oct 2003;36(4):267-78. [Medline].
6. Talkington DF, Shott S, Fallon MT, Schwartz SB, Thacker WL. Analysis of eight commercial enzyme immunoassay tests for detection of antibodies to Mycoplasma pneumoniae in human serum. Clin Diagn Lab Immunol. Sep 2004;11(5):862-7. [Medline].
7. Suzuki S, Yamazaki T, Narita M, et al. Clinical evaluation of macrolide-resistant Mycoplasma pneumoniae. Antimicrob Agents Chemother. Feb 2006;50(2):709-12. [Medline].
8. Klausner JD, Passaro D, Rosenberg J, et al. Enhanced control of an outbreak of Mycoplasma pneumoniae pneumonia with azithromycin prophylaxis. J Infect Dis. Jan 1998;177(1):161-6. [Medline].
9. Cunha BA. Liver involvement with Mycoplasma pneumoniae community-acquired pneumonia. J Clin Microbiol. Jul/2003;41(7):3456-7. [Medline].
10. Cunha BA. The Atypical Pneumonias: Clinical Diagnosis and Importance. Clin Microbiol Infect. May/2006;12 Suppl 3:12-24. [Medline].
11. Parchuri S, Cunha BA. Mycoplasma pneumoniae community-acquired pneumonia: Diagnostic usefulness of the agglutination-dissociation test. Infect Dis Pract. 2006;30:550-1.
12. Cunha BA. Pneumonia Essentials. 2^nd ed. Royal Oak, MI: Physicians Press; 2008.
13. Waites KB, Rikihisa Y, Taylor-Robinson D. Mycoplasma and Ureaplasma. In: Murray PR, Baron EJ, eds. Manual of Clinical Microbiology. 8^th ed. Washington, DC: ASM Press; 2003:972-90.

Article Last Updated: Mar 26, 2008