Pediatric Mycoplasma Infections 

Updated: Apr 17, 2018
Author: Archana Chatterjee, MD, PhD; Chief Editor: Russell W Steele, MD 


Practice Essentials

Mycoplasmal organisms are the smallest known free-living life forms. They are nearly ubiquitous in both the plant and animal kingdoms as colonizers and pathogens. They are prokaryotes but lack a cell wall. However, they have a unique cell membrane that contains sterols, which are not present in either bacteria or viruses. Mycoplasma organisms are small (150-250 nm) and have deformable membranes. The name Mycoplasma refers to the plasticity of the bacterial forms resembling fungal elements.

When they were first discovered, mycoplasmal organisms were believed to be viruses because they pass through filters that retain bacteria. However, unlike viruses, they are able to grow in cell-free media and contain both RNA and DNA. Mycoplasma species have also been mistakenly believed to be L-forms of bacteria, which also lack cell walls. Unlike mycoplasmal organisms, L-form bacteria do not have sterols in the cell membranes, and they can revert to their walled parental forms. The following summary is modified from Baum's "Introduction to Mycoplasma Diseases" in Principles and Practice of Infectious Diseases (see the image below).[1]

General characteristics of Mycoplasma species. General characteristics of Mycoplasma species.

The general characteristics of Mycoplasma species include the following:

  • Prokaryotic

  • Size of 150-250 nm

  • Lack of a cell wall

  • Sterol-containing cell membrane

  • Fastidious growth requirements

  • Fried-egg or mulberry colonies on agar

Mycoplasma species differ from viruses in the following ways:

  • They grow on cell-free media in vitro.

  • They contain both RNA and DNA.

  • They have both intracellular and extracellular parasitism in vivo.

Mycoplasma species differ from bacteria (including L-forms) in the following ways:

  • They have sterols in the cell membrane.

  • They share no DNA homology with known bacteria.

  • They have low guanine levels plus cytosine content.

  • Their genome has a low molecular weight.

  • They exhibit no reversion to walled forms.


Mycoplasma organisms cause infection primarily as extracellular parasites, attaching to the surface of ciliated and nonciliated epithelial cells of the respiratory and genital tracts. A unique group of membrane proteins allow this adherence.[2] The attachment site, or receptor, is a complex carbohydrate structurally akin to antigen I of RBCs. The antibody response to this receptor results in production of the anti-I antibody or cold agglutinin, which acts as an autoantibody. Following attachment, mycoplasmal organisms may cause direct cytotoxic damage to epithelial cells because of hydrogen peroxide generation or cytolysis via an inflammatory response mediated by mononuclear cells or antigen-antibody reactions.

Mycoplasma pneumoniae is one of the few Mycoplasma species that causes human disease.[3] Most M. pneumoniae –associated illnesses are confined to the respiratory tract; however, M. pneumoniae respiratory infections are also associated with various extrapulmonary manifestations.[4, 5, 6, 7, 8, 9] The pathogenesis of extrapulmonary complications is unknown but is thought to be an immunomediated mechanism.[10] Systemic spread of the bacterium is rare. Genital mycoplasmal organisms are associated with numerous genitourinary tract and reproductive diseases but also can cause infections at other sites.[1]

Genital mycoplasmal organisms (eg, Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma genitalium, Ureaplasma species) are sexually transmitted. Colonization rates for M. hominis and Ureaplasma species are 20-50% and 40-50%, respectively. These organisms are associated with numerous genitourinary tract and reproductive diseases and have been implicated in preterm labor and bacteremia in very preterm newborn infants.[11, 12, 13, 14]

Mycoplasmal organisms commonly contaminate tissue cultures, in which they act as intracellular parasites and alter both cellular and viral molecular events. They are difficult to eliminate, and they raise questions regarding the validity of molecular biology results from tissue-culture experiments.[1]



United States

The disease is distributed worldwide without regard to season.[3] Atypical organisms such as M. pneumoniae are implicated in as many as 40% of cases of community-acquired pneumonia.[15, 16] In the United States, at least 1 case of mycoplasmal pneumonia per 1000 persons is estimated to occur each year, or more than 2 million cases annually. The rates are rising in the central United States.[17] The incidence may be much higher because most mild-to-moderate cases are treated empirically.


One study focused on the epidemiological and clinical features of an M. pneumoniae outbreak in a kindergarten class in Beijing, China.[18] The report determined that the outbreak was caused by poor ventilation in a temporary classroom.


Most M. pneumoniae infections lead to clinically apparent disease involving the upper respiratory tract; the symptoms include pharyngitis, cough, headache, chills, and myalgias.[1] In 5-10% of patients (with the rate depending on age), the infection progresses to tracheobronchitis or pneumonia and is usually self-limited. Pleural effusion (usually small) occurs in 5-20% of patients.[1] M. pneumoniae has been strongly implicated in the pathogenesis of asthma, leading to acute and chronic wheezing in some individuals.[19, 20, 21, 22, 23]

Precedent M. pneumoniae respiratory infections have also been implicated in patients who present with extrapulmonary illness. The most common sites of extrapulmonary manifestations are dermatologic (25%) and CNS (1-10%), although cardiac, musculoskeletal, hematologic, and GI symptoms have also been reported.[6, 8, 9]

Children with compromised immunity, including those with humoral immunodeficiencies, are more likely to experience complications.[3, 10] In individuals with sickle cell anemia, mycoplasmal infection may be severe, with acute chest syndrome reported.[24] Unusually severe M. pneumoniae infection has also been reported in children with Down syndrome, especially those with congenital heart disease.[1]


Patients with sickle cell disease or related hemoglobinopathies are at increased risk for severe M. pneumoniae infections and may develop large pleural effusions and marked respiratory distress.[24] Those who develop extremely high cold agglutinin titers may experience digital necrosis.[1] Because sickle cell disease and other related hemoglobinopathies are most common among blacks, severe complications of mycoplasmal infections also occur most frequently in this group of patients.

Genital Mycoplasma species have been isolated more frequently from black men and women than from white men and women.[25] Ureaplasma species are found 4 times more often than M. hominis.


No effect is observed according to sex of the patient on the frequency or severity of M. pneumoniae infections. Colonization with Ureaplasma organisms and M. hominis primarily occurs as a result of sexual contact. Both have been found more often in women than in men and more often in infant girls than in infant boys.[10]


Children younger than 3 years primarily develop upper respiratory infection.[26] M. pneumoniae infection is uncommon in the first year of life; however in neonates, it may cause severe respiratory disease and extrapulmonary illness.[1] M. pneumoniae infection is common in school-aged children and adolescents, with the highest rate of infection in individuals aged 5-9 years, in whom the tendency is to develop bronchitis and pneumonia.[1] An outbreak in 2009 in Japan in 2 schools was attributed to the close contact of students.[27]

Colonization of infants by genital Mycoplasma species usually occurs during passage through an infected birth canal, and genital mycoplasmal organisms have been isolated from the upper respiratory tract in 15% of infants.[1] Colonization usually does not persist beyond 2 years.[10]

A population-based cross-sectional study that included 37 preschool and 55 school-age children who tested positive for M. pneumoniae reported that compared to school-age children, preschool children infected with M. pneumoniae had significantly higher risk (60% vs 42%) of severe disease (severe pneumonia).[28]




Symptoms of Mycoplasma pneumoniae infection are often nonspecific. The onset is usually insidious, with fever, malaise, headache, and cough. Cough is a hallmark of M. pneumoniae infection.[4, 12, 15, 16] The frequency and severity of cough may increase over the few days after onset and may become debilitating. In patients in whom the infection progresses to lower respiratory tract disease, the original symptoms persist, with a worsening and relatively nonproductive cough. On occasion, white or blood-flecked sputum and parasternal chest pain may be present as a result of muscle strain. Otitis media and sinusitis are uncommon. Postinfectious bronchitis may persist for weeks. M. pneumoniae infection may complicate asthma and exacerbate chronic obstructive pulmonary disease,[29] and acute asthma may be the first manifestation ofinfection.[19, 20, 21, 22, 23, 30, 31, 32]

Infection by genital mycoplasmal organisms may have diverse manifestations, including burning micturition (nongonococcal urethritis); prostatic pain, fever, and chills (suggestive of pyelonephritis); vaginal discharge; symptoms of pelvic inflammatory disease; postpartum fever; and postabortal fever.[1, 33, 34, 35, 36, 37, 38, 39] Neonates may present with symptoms of cough, meningitis, or brain abscess.[40, 41]


Patients with M. pneumoniae infection usually do not appear ill, and the illness often has been termed "walking pneumonia".[1, 3, 4, 15, 16] The pharynx may be erythematous without cervical adenopathy. Bullous myringitis is a classic but rare complication. Examination of the chest and lungs may yield little abnormality. A hallmark of M. pneumoniae infection is the disparity between physical findings (relatively few) and radiographic evidence of pneumonia.[42] Wheezing can occur, especially in patients with asthma.[21, 22, 23, 43] Rarely, fulminant pneumonia with respiratory failure can occur.[19, 20, 21, 22, 23]

Physical findings of genital Mycoplasma infection vary depending on the type of infection.[44, 45] Neonates, especially premature infants, may present with wheezing, retractions, and respiratory failure or signs of meningitis/brain abscess (eg, seizures, lethargy, neurologic deficits).[14, 40, 41]

Extrapulmonary manifestations of M. pneumoniae infection may or may not involve respiratory symptoms and include the following:

  • Dermatologic manifestations (most common)[4, 5, 6, 8, 46, 47, 48, 49, 50, 51, 52]

    • Erythematous macular and/or morbilliform rash

    • Papulovesicular exanthem

    • Erythema multiforme

    • Stevens-Johnson syndrome (with or without the classic skin lesions)

    • Erythema nodosum

    • Mucositis

  • Urticarial manifestations - Raynaud phenomenon

  • Cardiac manifestations

    • Arrhythmia and/or ECG abnormalities (conduction defects)

    • Congestive failure

    • Pericarditis

    • Myocarditis

    • Endocarditis

  • Neurologic/psychiatric manifestations[5, 7, 9, 53, 54]

    • Encephalitis and meningoencephalitis

    • Transverse myelitis

    • Aseptic meningitis

    • Peripheral neuropathies and radiculopathies

    • Brainstem dysfunction

    • Dysfunction of the pyramidal or extrapyramidal tract

    • Cerebellar dysfunction

    • Cerebral infarction

    • Guillain-Barré syndrome

  • Musculoskeletal manifestations[55, 56, 57]

    • Polyarthralgias

    • Acute arthritis (monoarticular or migratory)

    • Digital necrosis

  • Hematologic manifestations

    • Immune hemolytic anemia[53, 58, 59, 60]

    • Pancytopenia

    • Splenic infarct

    • Hemophilia-like illness


M. pneumoniae causes infections leading to clinically apparent disease involving the upper respiratory tract. In 5-10% of patients, depending on age, the infection progresses to tracheobronchitis or pneumonia. M. hominis causes genital mycoplasmal infections, which may result in diverse manifestations.



Differential Diagnoses



Laboratory Studies

Diagnostic tests for M. pneumoniae are most useful in hospitalized children who may be at risk for fulminant pulmonary disease and complications of extrapulmonary illness. Otherwise, clinical and epidemiologic data can guide the care of the ambulatory patient.

  • Tests for M. pneumoniae[61]

    • Bacterial culture is of little practical value because of fastidious growth requirements and slow growth.

    • Serologic diagnosis has been the mainstay of laboratory testing.

      • The cold agglutinin test may be performed at the bedside or in the laboratory. Serum from spun patient blood is combined with type O erythrocytes and incubated at 4°C for several minutes. The degree of agglutination is noted at this temperature and again after rewarming to 37°C to confirm resolution of the agglutination. The serum is diluted serially, and the test is repeated. The highest dilution resulting in agglutination at 4°C is reported as the cold agglutinin titer. The sensitivity of this test is 50-90%, and the specificity is approximately 75%.[1, 10]

      • Paired acute and convalescent sera are best for complement-fixation serology. A positive result requires a more than 4-fold rise in titer between acute and convalescent sera and more than 1:32 titer in a single serum specimen (86-90% sensitive and 87-94% specific). The test is not helpful in guiding diagnostic and therapeutic decisions because elevations in antibody titer may take as long as 3-4 weeks after the onset of disease. Additionally, the antibody response can be diminished or absent in immunosuppressed hosts and infants.[1, 10]

      • Enzyme-linked immunoassay is used to detect immunoglobulin M (IgM) and immunoglobulin G (IgG) directed against M. pneumoniae. Specificity is greater than 99%, and sensitivity is 98% when both findings are obtained. The IgM result may be negative early (at 7-10 d) and may not be helpful in guiding initial therapy.[62]

    • Direct antigen detection in sputum specimens is performed using antigen-capture indirect enzyme immunoassay. Relatively high specificity and sensitivity (91%) are achieved.

    • Detection of nucleotide sequences with a commercially available kit is based on radioiodine-labeled DNA complementary to M. pneumoniae ribosomal RNA. Sensitivity and specificity were 89% in 1 study.

    • Seminested polymerase chain reaction (PCR) assay using 16S ribosomal DNA (rDNA) as a target and real-time PCR assays targeting the gene for P1 adhesion protein are available.[63, 64, 65] They do not rely on an immunologic response; therefore, relatively early detection is possible. Both techniques have high sensitivity and high specificity. Real-time PCR assays have the advantage of speed and the ability to analyze numerous samples.

  • Tests for genital mycoplasmal organisms

    • These organisms are usually detected by means of cultures in special media (beef-heart infusion broth with fresh yeast extract and horse serum), followed by subcultures on agar media. Ureaplasma species usually grow within 1-2 days, and M. hominis grows within 1 week, but Mycoplasma genitalium may require 1-2 months to grow.

    • Antibody studies, organ cultures, and animal inoculation have all been used, but they have little practical application in routine diagnostic laboratories. PCR techniques using clinical specimens from the upper genital tract obtained during laparoscopy may be of value in the future.

Imaging Studies

Chest radiographs demonstrate characteristic features of M. pneumoniae infection: bilateral pulmonary involvement, multifocal or diffuse disease, and reticular infiltrates.[42] In rare cases, pleural effusions may be superimposed on parenchymal disease; however, one study reported a 23% incidence rate.[42] Late in the course, pleural effusions may be the only remaining feature. Hilar lymphadenopathy can be present in 7-22% of pediatric patients.

High-resolution CT may reveal the lobular distribution, centrilobular involvement, and interstitial abnormalities in M pneumoniae pneumonia better than chest radiography.[13] However, high-resolution CT is more expensive, and radiation exposure is increased. High-resolution CT is usually not indicated in the routine workup of all patients.


Because most infections tend to be mild, few diagnostic procedures need to be performed. In severe lower respiratory infection caused by M. pneumoniae, bronchoalveolar lavage with appropriate testing of the lavage fluid may be needed; antigen detection, PCR, and culturing are used.[61, 62, 63, 64, 65] In the presence of neurological disease of unknown etiology, investigating Mycoplasma serologically and using cerebrospinal fluid (CSF) analysis is prudent.[53]

Histologic Findings

The histopathology of M. pneumoniae infection is limited to the ciliated respiratory epithelium extending from the trachea to the respiratory bronchiole. The airways are surrounded by mononuclear cell infiltrates. Intraluminal infiltrates may include polymorphonuclear cells and mononuclear cells.[3]



Medical Care

Antimicrobial therapy is not necessary for mycoplasmal infection of the upper respiratory tract.

An increase in macrolide-resistant M pneumoniae (MRMP) has been reported.[66, 67] This resistant form can be associated with prolonged severe respiratory infection in children.[68] Although pneumonia is self-limiting and is not life threatening in most patients, treatment with appropriate antimicrobials may shorten the duration of illness and perhaps reduce spread to contacts.

Using genotypic and phenotypic methods, Zheng et al detected high-level MRMP in 13.2% of 91 M pneumoniae–positive specimens from 6 United States locations. Macrolides should remain the drugs of choice in children with M pneumoniae respiratory infections, but with the emergence of high-level MRMP in all 6 centers throughout a broad geographic area in the United States, clinicians should be vigilant for macrolide treatment failures.[69]

Management of genitourinary diseases in which Mycoplasma species may play a role depends on recognizing the clinical syndromes for which antimicrobial therapy may be appropriate. Consider using antimicrobials that are active against mycoplasmal organisms in nongonococcal urethritis and pelvic inflammatory disease. Extrapulmonary complications are likely to be associated with an autoimmune response; thus, immunosuppressive therapy using steroids and intravenous immunoglobulin may be helpful.[53, 70]


Surgical Care

Surgical treatment is typically not needed.


Although consultations are usually not needed, in severe cases, admission to the ICU and consultation with critical care specialists, pulmonologists, and infectious disease physicians may be warranted. In patients who present with extrapulmonary manifestations, consult appropriate subspecialists.


Activity is as tolerated by the patient.



Medication Summary

As a result of the lack of a cell wall, beta-lactams are ineffective; neither is the combined therapy of trimethoprim and sulfamethoxazole effective. Aminoglycosides are effective in vitro, but efficacy is unknown in vivo.

Macrolides are the agents of choice. Alternatively, tetracyclines may be used in patients older than 8 years. Fluoroquinolones may be considered if macrolides or tetracyclines are not suitable choices; however, most fluoroquinolones are not approved by the FDA for use in patients younger than 18 years.[2, 3, 10, 71]

Ketolides show effective activity against mycoplasmal organisms. Telithromycin has been shown to be active against M. pneumoniae. It is approved for treatment of community-acquired pneumonia. Because of the risk of hepatotoxicity associated with telithromycin, the US Food and Drug Administration (FDA) removed previously approved indications for sinusitis and acute bacterial exacerbations of chronic bronchitis.

Streptogramins (ie, quinupristin-dalfopristin) are available only as a parenteral formulation; therefore, they are not practical for use in patients with Mycoplasma diseases.


Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Because of reports of macrolide resistance, whenever feasible, guide antibiotic selection using culture sensitivity.[2, 3, 10]

Erythromycin (E.E.S., E-Mycin, Eryc)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer RNA (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine proper dosage.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, arresting RNA-dependent protein synthesis.

Azithromycin (Zithromax)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, arresting RNA-dependent protein synthesis.

Tetracycline (Sumycin)

Treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits.

Doxycycline (Vibramycin)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits of susceptible bacteria.

Levofloxacin (Levaquin)

Of the fluoroquinolones (eg, ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin, grepafloxacin), drug of choice (DOC) to treat community-acquired pneumonia in adults. Use in children and pregnant women restricted because of concern regarding cartilage toxicity, but several clinical trials ongoing, and such use may be indicated in the future.

Telithromycin (Ketec)

First antibiotic in new ketolides class. Combats resistant bacteria by inhibiting protein synthesis necessary for bacterial reproduction, binding 10 times tighter than macrolides at 2 sites on bacterial ribosomes. Blocks protein synthesis by binding to 50S ribosomal subunit (23S rRNA at domains II and V). Binding at domain II retains activity against gram-positive cocci (eg, Streptococcus pneumoniae), eliminating resistance mediated by methylases (erm genes) that alter domain V binding site. May also inhibit the assembly of nascent ribosomal units. Resistance and cross resistance have not been observed.

Active against S pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis; as well as atypical bacteria such as Chlamydia pneumoniae, M. pneumoniae, and Legionella pneumoniae. Indicated to treat mild-to-moderate community-acquired pneumonia, including infections caused by multidrug resistant S pneumoniae).



Further Outpatient Care

Routine follow-up visits are usually not required because the response to therapy is generally excellent.

Further Inpatient Care

Further inpatient care in patients with Mycoplasma infections is usually necessary only if severe pneumonia or extrapulmonary complications occur.

Inpatient & Outpatient Medications

See Medical Care.


Transfer is usually necessary only if severe pneumonia or extrapulmonary complications occur and if appropriate medical facilities for treatment are not available locally.


Early research efforts to develop a vaccine have thus far been disappointing, and no new developments are on the horizon.[3]


Complications are relatively rare. See Extrapulmonary manifestations of M pneumoniae infection.


Prognosis for Mycoplasma infections is usually excellent; however, if complications occur, long-term sequelae may result.

Patient Education

Patient education regarding the common occurrence, relatively mild nature, appropriate therapy, and usually complete recovery from Mycoplasma infection is important.