Mycoplasma Infections (Mycoplasma pneumoniae)

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 usually are 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.

M pneumoniae is perhaps best known as the cause of community-acquired walking or atypical pneumonia, but the most frequent clinical syndrome caused by this organism is actually tracheobronchitis or bronchiolitis, often accompanied by upper respiratory tract manifestations. Pneumonia develops in only 5-10% of persons who are infected. Acute pharyngitis may also occur.[1] Recent evidence has also implicated M pneumoniae with prolonged ventilator course and hypoxemia in adults with suspected ventilator-associated pneumonia. However, the presence of other microorganisms in many of these patients makes it difficult to assess the true role of M pneumoniae as a causative pathogen in this setting.[2]

After inhalation of respiratory aerosols, the organism attaches to host epithelial 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 hydrogen peroxide. M pneumoniae has been shown to produce an exotoxin that is also believed to play a major role in the damage to the respiratory epithelium that occurs during acute infection.[3] This toxin, named the community-acquired respiratory disease toxin (CARDS) is an ADP-ribosylating and vacuolating cytotoxin similar to pertussis toxin.[4]

Evidence from animal models of M pneumoniae infection have proven that recombinant CARDS toxin results in significant pulmonary inflammation, release of proinflammatory cytokines, and airway dysfunction.[5] Variation in CARDS toxin production among M pneumoniae strains may be correlated with the range of severity of pulmonary disease observed among patients.[4] The organism also has the ability to exist and possibly replicate intracellularly, which may contribute to chronicity of illness and difficult eradication.[1] Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma.[6] More extensive information on the pathogenesis of mycoplasmal respiratory infections is available in review articles and book chapters.[1, 6, 7]  

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. The mean incubation period is 20-23 days. The organism may persist in the respiratory tract for several months, and sometimes for years in patients who are immunosuppressed, after initial infection.[8]

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 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. Slow spread throughout households is common, with a mean incubation period of 20-23 days. 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. Studies have indicated that M pneumoniae is second only to Streptococcus pneumoniae as a cause of bacterial pneumonia that requires hospitalization in elderly adults.[9] 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.[1]

Recent evidence suggests that M pneumoniae disease is sometimes much more severe than appreciated, even in otherwise healthy children and adults.[6] Severe disease is more common in persons with underlying disease or immunosuppression. Detection of CARDS toxin or antitoxin antibodies in bronchoalveolar lavage fluid obtained from persons with suspected ventilator-associated pneumonias in association with prolonged ventilator course and hypoxemia suggest this organism may be of considerable significance among trauma patients in intensive care units.[2]

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.[10]

Most patients with respiratory infections caused by M.pneumoniae will respond to oral antimicrobial treatment in an outpatient setting. Elderly persons, very young infants, and persons with iimmunodeficiencies may have a harder time recovering and eradicating the organism. In some instances chronic infection can ensue. Additionally, there are some reports of fulminant and ultimately fatal cases of M pneumoniae infection in otherwise healthy persons.

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

Symptoms may include the following:

• 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 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 include the following:

• 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).[1, 6]  

This is a bacterial infection caused by M pneumoniae.

Role in Asthma

M pneumoniae has evolved to create persistent infection and has been associated with development of asthma or atopic disease in persons who appear to have less robust immune responses to respiratory infections. Research in this area has been summarized in a review.[1] Epidemiologic studies have yielded evidence that M pneumoniae infection, diagnosed primarily by serology is associated with the development of asthma. Patients with M pneumoniae infection had a higher risk of developing asthma than matched controls, and this risk was further augmented by comorbidities such as atopic disease.

Studies of acute asthma in hospitalized children or adults revealed an incidence of M pneumoniae ranging from 4.5% to 65%. Other studies have reported a very high prevalence of M pneumoniae in chronic asthma, even in the absence of exacerbation. There have been reports that a course of macrolide antibiotics active against M pneumoniae will shorten the duration of wheezing episodes in children, but it is unclear whether antimicrobial activity of macrolides, anti-inflammatory activity, or a combination is behind the protective effect of this class of medication in asthma and asthma-like diseases. Many children with asthma also receive corticosteroids, which further complicates interpretation of antimicrobial effects on M pneumoniae in reducing severity and/or duration of asthma. Studies using murine animal models suggest that allergic airway inflammation downregulates the host response to M pneumoniae and provides a plausible explanation for reports of increased prevalence of M pneumoniae in chronic asthma as well as a potential role in the pathogenesis and perpetuation of this inflammatory respiratory disease.

Extrapulmonary Manifestations

M pneumoniae is well recognized for producing a broad array of extrapulmonary manifestations that can affect almost every organ in the body. Even though many different extrapulmonary manifestations of M pneumoniae infection have been characterized, they usually are not specific enough to confirm the diagnosis.

Three different mechanisms have been proposed for extrapulmonary complications of M pneumoniae infection. The first is a direct effect of the bacteria that are present at the site of inflammation mediated by cytokine release by the host. The second is through the production of autoimmunity or immune complexes. The third is by the production of vasculitis or thrombosis as a result of cytokines and chemokines such as TNF-α and IL-8 or by immunomodulation through mediators such as complement and fibrin D-dimers.

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.[11, 12]

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.

Patients may have an elevated erythrocyte sedimentation rate (ESR).

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 community-acquired pneumonia, the more likely the cold agglutinins are due to M pneumoniae. No specific abnormalities of hepatic or renal function are likely to occur.[12, 13, 14]

To confirm mycoplasmal respiratory tract infection, culture, molecular-based tests, and/or serological tests are necessary.

Culture

Respiratory tract specimens suitable for culture include throat swabs, sputum, tracheal aspirates, nasal swabs, bronchial lavage fluid, pleural fluid, or lung biopsy tissue, depending on the patient's clinical condition. Other body fluids such as CSF or synovial fluid, and tissues obtained by biopsy, including skin lesions or heart valve tissue also may be cultured as necessary in the presence of extrapulmonary manifestations. 

Mycoplasmal organisms have fastidious growth requirements and often are difficult and slow to grow in vitro. Take care during specimen collection to inoculate into a suitable transport medium (eg, SP4 broth or universal transport medium), 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 or longer in some cases, and the culture is not extremely sensitive for detecting M pneumoniae infection. The culture medium often is unavailable except from specialized reference laboratories. If culture is attempted, alternative procedures including serology and/or molecular-based nucleic acid amplification tests also should be performed.[10]

Serologic testing

Physicians can use serology to confirm M pneumoniae infection even though these tests suffer from significant problems.

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 some researchers purport that single-titer immunoglobulin M (IgM) or immunoglobulin A (IgA) assays reveal current infection, IgM may persist for up to several months in some people, and many adults may not mount a detectable IgM response. Therefore, relying on a single serologic 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

Qualitative, rapid, single-specimen, membrane-based enzyme-linked immunosorbent assays readily adaptable to the primary care physician's office laboratory have been available for several years.[15]

The Remel IgG/IgM Antibody Test System (Thermo-Fisher) measures both IgG and IgM simultaneously.

The Meridian ImmunoCard (Meridian Bioscience, Inc) 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, although erroneous results sometimes are obtained when only single serum samples are analyzed.[15, 16]

Both tests have a moderate complexity classification under the Clinical Laboratory Improvement Amendment (CLIA), allowing many physicians to offer serologic assays for M pneumoniae antibodies as point-of-care tests so that they 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) or other technologies. A variety of gene targets have been described for PCR assays to detect M pneumoniae in clinical specimens. Traditional PCR is gradually being replaced by quantitative real-time PCR assays. Publications indicate that the CARDS toxin gene is more sensitive for M pneumoniae detection than assays targeting the P1 protein or ATPase genes.[17]

Some reference laboratories offer PCR assays that they developed themselves for detection of current mycoplasmal infection. Several molecular-based multiplex PCR tests for detection of M pneumoniae and other viral and bacterial respiratory pathogens are now FDA-approved for use in the United States, and their accuracy in detecting M pneumoniae in nasal swabs has been compared.[18]  These integrated sample-to-answer tests can provide results in about an hour.

A singleplex test that detects only M pneumoniae in throat swabs is the Alethia Mycoplasma Direct Assay (Meridian Bioscience, Inc). This loop-mediated isothermal amplification (LAMP) assay enables detection of M pneumoniae in up to 10 clinical specimens that can be tested simultaneously within one hour without the need for expensive equipment. It has a moderate complexity CLIA classification so it can be offered through physician office laboratories as well as hospital laoratories, making it the closest thing to a point of care test that is currently available for direct detection of M pneumoniae in clinical specimens.[19]  

Carriage of mycoplasmas in the upper respiratory tract for variable periods following prior infection may confound the interpretation of a single positive PCR 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 can be accompanied by serologic 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]

Given the significant limitations of serology, prolonged turnaround time, insensitivity of culture, and the growing availability of rapid diagnosis of mycoplasmal infection in symptomatic patients by molecular-based assays, molecular-based tests are now the preferred method for diagnosis of M pneumoniae infection when available to primary care physicians through a hospital or reference laboratory. The automated multiplex PCR platforms are designed to test nasal swabs and provide their own specimen collection kits and transport systems. 

Some reference laboratories can perform lab-developed PCR assays on non-respiratory specimens obtained to evaluate direct invasion of extrapulmonary sites such as CSF, heart valves, kidney biopsies, skin lesions, and synovial fluids. None of the FDA-cleared commercial PCRs have been validated to test non-respiratory specimens.

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.

The histologal appearance of mycoplasmal pneumonia typically shows a patchy interstitial pneumonia, especially involving the lower lobes of the lungs, with swollen alveolar lining cells, bronchiolar walls thickened by congestion and edema, and an intraluminal exudate of neutrophils, epithelial cells, and proteinaceous debris.

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 often is 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.

Antimicrobial therapy

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 radiologic 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.

M pneumoniae is only one of several bacterial pathogens that cause community-acquired pneumonias (CAP) with overlapping clinical presentations. It is impractical and even impossible to identify a microbiologic etiology in an ambulatory care setting or even a hospital setting when empiric antimicrobial treatment should be begun in a timely manner. Therefore, various professional organizations have published guidelines for diagnosis and management of CAP which are updated at periodic intervals taking into account changes in epidemiology of likely microbial causes and emergence of acquired antimicrobial resistance.

The American Thoracic Society (ATS) has joined with the Infectious Diseases Society of America (IDSA) to publish a guideline for adults, whereas the Pediatric Infectious Diseases Society (PIDSA) has joined with the IDSA to publish guidelines for children. The ATS/IDSA guidelines published in 2019 do not address laboratory testing or specific antimicrobial treatment directed at M pneumoniae, nor do they address the issue of treatment failures due to macrolide resistance. However, these guidlines for CAP, including moderate or severe illness, all incorporate macrolides, doxycycline, and/or fluoroquinolones into their recommendations. These antimicrobial agents should provide adequate coverage for M pneumoniae infections except for some of those that may be due to macrolide-resistance organisms.[20]

The PIDS/IDSA guidelines for CAP in children published in 2011[21]  recommend testing for M pneumoniae if laboratory results can be available within a clinically relevant timeframe. Note that these guidelines were published prior to the widespread availablity of FDA-cleared automated commercial PCRs to detect M pneumoniae. This guideline recommends primary treatment with a macrolide with levofloxacin as a secondary choice, even though they do not specifically address the issue of clinically significant macrolide resistance in M pneumoniae. Over the past several years, there have been reports of successful treatment of children with macrolide-resistant M pneumoniae infections with levlfloxacin, so this recommendation appears to be justified.[1]  

Oral erythromycin or one of the newer macrolides such as azithromycin or clarithromycin have long been the DOC for mycoplasmal respiratory tract infections. Tetracycline and its analogues also are 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. Fluoroquinolones such as levofloxacin or moxifloxacin exhibit bactericidal antimycoplasmal activity but generally are 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 S 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 drugs, including fluoroquinolones, have been approved for the treatment of mycoplasmal respiratory infections with shorter courses because of their favorable pharmacokinetics and tolerability.

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 often are diagnosed late in the course of disease, the benefit of early treatment is unknown.

Since 2000, macrolide-resistant M pneumoniae caused by point mutations in domain V of 23S ribosomal RNA has emerged in Asia and has now been reported in Europe and North America. Surveillance conducted primarily in pediatric populations has documented resistance rates of 46%-93% in Japan, 69%-97% in China, 12.3%-23% in Taiwan, 61.3% in South Korea, 30% in Israel, and 9.8% in France. A nationwide survey of macrolide resistance performed in the United States between 2016 and 2018 revealed a macrolide resistance rate of  7.5% overall.  Prevalence of resistance was significantly higher in the South and East (18.3%) than in the West (2.1%).[22]

Macrolide resistance has also been documented in adults, but to a lesser extent. Selection of resistance during macrolide therapy has been documented in children in France, Italy, and Israel.

While there are no apparent differences in initial presentation to distinguish a patient with macrolide-resistant M pneumoniae, when such infections occur, they often are clinically significant, resulting in prolonged fever, coughing, longer hospital stays, or worsening findings on chest radiographs compared with persons with infections caused by susceptible strains.[23, 24, 25, 26]

The spread of macrolide resistance has led to development of real-time PCR-based assays to detect resistance genes directly in clinical specimens since cultures and conventional susceptibility tests require much longer time and culture may be falsely negative.[24, 25, 26]  None of these tests are FDA-cleared for use in the United States, but macrolide resistance testing is available through specialized reference laboratories using lab-developed PCR assays. In view of the increasing spread of macrolide resistance, clinicians are advised to monitor patient outcomes and to consider using alternative antimicrobial agents (eg, minocycline, doxycycline, fluoroquinolones) if an initial treatment with a macrolide is unsuccessful.[27]

Class Summary

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

Erythromycin (E-Mycin, Ery-Tab, E.E.S.)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl 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. When bid dosing desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Clarithromycin (Biaxin, Biaxin XL)

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

Azithromycin (Zithromax)

Semisynthetic antibiotic belonging to the macrolide subgroup of azalides and is similar in structure to erythromycin. Inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action generally is bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms.

Doxycycline (Vibramycin)

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

Minocycline (Minocin)

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

Levofloxacin (Levaquin)

Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Moxifloxacin (Avelox)

Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

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 usually are not necessary unless the illness fails to respond to therapy, which would raise questions about the accuracy of the microbiologic diagnosis or the possibility of chronic infection, which sometimes occurs.

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.

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.[28]

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.

Isolation

Because of the endemicity of infection with M pneumoniae in susceptible populations, isolating patients is seldom practical and generally is not recommended.

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.[15]  

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 been detected by culture and/or PCR directly from cerebrospinal, pericardial, and synovial fluids and from other extrapulmonary sites, always consider direct invasion by this organism and order appropriate diagnostic testing for confirmation.

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

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.