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Author: Michael J Bono, MD, FACEP, Professor of Emergency Medicine, Associate Director of Emergency Medicine Residency Program, Department of Emergency Medicine, Eastern Virginia Medical School

Michael J Bono is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American Heart Association, Medical Society of Virginia, and Society for Academic Emergency Medicine

Editors: Joseph A Salomone, III, MD, Associate Professor, Department of Emergency Medicine, Truman Medical Center, University of Missouri at Kansas City School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Paul Blackburn, DO, FACOEP, FACEP, Program Director, Department of Emergency Medicine, Maricopa Medical Center; Assistant Professor, Department of Surgery, University of Arizona; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System

Author and Editor Disclosure

Synonyms and related keywords: mycoplasma pneumonia, mycoplasmal pneumonia, Mycoplasma pneumoniae, M pneumoniae, CAP, community-acquired pneumonia, atypical pneumonia, sore chest, tracheal tenderness, dry cough, bullous myringitis, pharyngeal erythema, scratchy sore throat



Background

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, and, usually, the disease has a prolonged, gradual onset. M pneumoniae was first isolated in cattle with pleuropneumonia in 1898. In 1938, Reimann described the first cases of mycoplasmal pneumonia in man. Reimann coined the term "primary atypical pneumonia" after observing 7 patients in Philadelphia with marked constitutional symptoms, upper and lower respiratory tract symptoms, and a protracted course with gradual resolution. Peterson discovered the phenomenon of cold agglutinin in 1943, and high titers of cold agglutinins in patients with this type of pneumonia were discovered accidentally. In 1944, Eaton was credited with discovering a specific agent, coined Eaton's agent, as the principal cause of primary atypical pneumonia. First thought to be a virus, Eaton's agent was proved to be a Mycoplasma species in 1961.

For more information, see Medscape's Pneumonia Resource Center.

For a CME/CE activity, see CME/CE - Macrolides Improve Outcomes Among Elderly With Bacteremic Pneumonia.

Pathophysiology

The responsible organism, M pneumoniae, is a pleomorphic organism that, unlike bacteria, lacks a cell wall, and unlike viruses do not need a host cell for replication. The prolonged paroxysmal cough seen in this disease is thought to be due to the inhibition of ciliary movement. The organism has a remarkable gliding motility and specialized filamentous tips end that allows it to burrow between cilia within the respiratory epithelium, eventually causing sloughing of the respiratory epithelial cells.

The organism has two properties that seem to correlate well with its pathogenicity in humans. The first is a selective affinity for respiratory epithelial cells, and the second is the ability to produce hydrogen peroxide, which is thought to be responsible for much of the initial cell disruption in the respiratory tract and for damage to erythrocyte membranes.

The pathogenicity of M pneumoniae has been linked to the activation of inflammatory mediators, including cytokines.

Frequency

United States

M pneumoniae is now recognized as one of the most common causes of community-acquired pneumonia in otherwise healthy patients younger than 40 years, with the highest rate in 5- to 20-year olds. M pneumoniae causes upper and lower respiratory illness in all age groups, particularly in temperate climates, and in summer, may cause up to 50% of all pneumonias.

Mycoplasmal pneumonia can occur at any time of the year, but large outbreaks tend to occur in the late summer and fall. The incubation period tends to be smoldering and averages 3 weeks, in contrast to that of influenza and other viral pneumonias, which generally is a few days. Epidemics of mycoplasmal pneumonia tend to occur every 4-8 years in the general population and tend to be more frequent within closed populations, such as in military and prison populations. Although M pneumoniae is a common cause of pneumonia, only 5-10% of infected patients actually develop pneumonia.

Mortality/Morbidity

In almost all patients, the pneumonia resolves without any serious complications. M pneumoniae can cause severe pneumonia in children and has recently been associated with acute chest syndrome in patients with sickle cell anemia.   

Race

No racial predilections exist in mycoplasmal diseases.

Sex

No difference in disease frequency exists between males and females, but illnesses are somewhat more severe in males.  

Age

Mycoplasmal pneumonia is common in all age groups; however, it is most common in the first 2 decades of life and is rare in children younger than 5 years.



History

Mycoplasmal pneumonia is a disease of gradual and insidious onset of several days to weeks. The patient's history may include the following:

  • Fever
  • Malaise
  • Persistent, slowly worsening dry cough; absence of cough makes the diagnosis of M pneumoniae unlikely
  • Headache
  • Chills, not rigors
  • Scratchy sore throat
  • Sore chest and tracheal tenderness (result of the protracted cough)
  • Pleuritic chest pain (rare)

Physical

Most cases of pneumonia due to M pneumoniae resolve after several weeks, although a dry cough can be present for as long as a month; some patients can have a protracted illness lasting as long as 6 weeks. Other findings may also include the following:

  • A nontoxic general appearance
  • Erythematous tympanic membranes or bullous myringitis in patients older than age 2 years, an uncommon but unique sign
  • Mild pharyngeal injection with minimal or no cervical adenopathy, but no exudate
  • Normal lung findings with early infection but rhonchi, rales, and/or wheezes several days later
  • Various exanthems including erythema multiforme and Stevens-Johnson syndrome

Causes

  • The causative agent is M pneumoniae, a bacterium lacking a cell wall, which belongs to the class Mollicutes, the smallest known free-living microorganisms.
  • Because the organism can be excreted from the respiratory tract for several weeks after the acute infection, isolation of the organism may not indicate acute infection.



Pediatrics, Pneumonia
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Empyema and Abscess
Pneumonia, Immunocompromised
Pneumonia, Viral

Other Problems to be Considered

Chlamydia pneumoniae
Legionella pneumophila
Chlamydia psittaci
Chlamydia trachomatis
Coxiella burnetii (Q fever)



Lab Studies

  • The WBC count generally is not helpful, since results may be normal or elevated. Hemolytic anemia has been described, but it is rare.
  • Sputum Gram stains and cultures usually are not helpful, since M pneumoniae lacks a cell wall and cannot be stained. 
  • Elevated erythrocyte sedimentation rates may be present but are nonspecific.

Imaging Studies

  • Radiographic findings are variable, but abnormalities are usually more striking than the findings on physical examination. 
    • Bronchopneumonia often involves a single lower lobe. Lobar consolidation is rare.
    • Platelike atelectasis is noted as thin, flat areas of collapsed lung and often is seen on a lateral image of the chest.
    • Reticulonodular or interstitial infiltrates, primarily in the lower lobes, may resemble other diseases with granulomatous pathology, such as tuberculosis, mycoses, and sarcoidosis. 
    • Hilar adenopathy sometimes is mistaken for malignancy.
    • Pleural effusions develop in fewer than 20% of patients; when present, they can be seen on lateral decubitus films.
  • High-resolution CT scans of the chest are more sensitive than chest radiography in elucidating lung disease.

Other Tests

  • M pneumoniae is difficult to culture and requires 7-21 days to grow; culturing is successful in only 40-90% of cases and does not provide information to guide patient management.
  • Serology tests that demonstrate a 4-fold or greater increase or decrease in paired sera titers or a single titer greater than or equal to 1:32
    • Serum cold agglutination is a nonspecific test for M pneumoniae, but findings are positive in 50-70% of patients after 7-10 days of infection. Cold agglutinin tests can be obtained from diagnostic laboratories. A negative result does not exclude infection, and this test may be affected by cross-reactions with other pathogens, such as adenovirus, Epstein-Barr, and measles viruses. A quick bedside test can be performed by partially filling a purple-top tube with blood and placing it in ice; a positive finding is one in which "grains of sand" appear on the glass portion of the tube.
    • Other serological tests include complement fixation, enzyme-linked immunoassay, and indirect hemagglutination. All of these have acceptable sensitivity and specificity.
  • Polymerase chain reaction
    • Polymerase chain reaction (PCR) has been shown to accurately diagnose atypical pneumonia and has been used for epidemiologic studies, but it is currently not used in most clinical settings. Real-time PCR is a promising test that allows detection of M pneumoniae DNA in all phases of infection, including early periods when the serum may be negative for antibody.
    • A radiolabeled DNA probe detects M pneumoniae ribosomal RNA in respiratory secretions with 90% sensitivity.
    • Eosinophil cationic protein (ECP) has been studied in M pneumoniae infection and asthma and may show some promise. ECP measures damage to the respiratory epithelium.



Emergency Department Care

Mycoplasmal pneumonia should be considered as a possible etiology in any emergency department patient presenting with 3 weeks of a steadily progressive cough. Patients are usually not critically ill, but seek relief from the persistent, worsening cough. Occasionally, various pulmonary and extrapulmonary complications may occur and may require emergent attention.



Several antimicrobials are effective in reducing the length of illness due to mycoplasmal pneumonia.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. In the treatment of mycoplasmal pneumonia, antimicrobials against M pneumoniae are bacteriostatic, not bactericidal.

Drug NameErythromycin (EES, Erythrocin, E-mycin)
DescriptionInhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes and causing RNA-dependent protein synthesis to arrest; for treatment of staphylococcal and streptococcal infections.
Adult Dose500 mg PO qid for 7-10 d
Pediatric Dose7.5-12.5 mg/kg/dose PO qid for 7-10 d
ContraindicationsDocumented hypersensitivity; hepatic impairment
InteractionsCoadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCaution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug NameAzithromycin (Zithromax)
DescriptionVery effective against M pneumoniae. Perhaps the most common agent used to treat M pneumoniae given its ease of administration.
Adult DoseDay 1: 500 mg PO
Days 2-5: 250 mg/d PO
Pediatric Dose<6 months: Not established
>6 months: day 1: 10 mg/kg PO once; not to exceed 500 mg/d; days 2-5: 5 mg/kg/d PO; not to exceed 250 mg/d
ContraindicationsDocumented hypersensitivity; hepatic impairment; do not administer with pimozide
InteractionsMay increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsSite reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Drug NameClarithromycin (Biaxin)
DescriptionReversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating the dissociation of peptidyl tRNA from ribosomes; result is bacterial growth inhibition.
Adult Dose500 mg PO bid for 7-14 d
Pediatric Dose<6 months: Not established
>6 months: 7.5 mg/kg/dose PO bid for 10 d
ContraindicationsDocumented hypersensitivity; coadministration of pimozide
InteractionsToxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG CoA-reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCoadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Drug NameDoxycycline (Vibramycin)
DescriptionTreats susceptible bacterial infections of both gram-positive and gram-negative organisms, as well as infections caused by Mycoplasma, Chlamydophilia, and Rickettsia organisms; inhibits bacterial protein synthesis by binding with the 30S subunit and possibly the 50S ribosomal subunit of susceptible bacteria; as effective as erythromycin and other macrolides in the treatment of M pneumoniae infection.
Adult Dose100 mg PO bid for 1-4 wk
Pediatric Dose<8 years: Not recommended
>8 years: 2-4 mg/kg/d up to 200 mg/d PO divided bid
ContraindicationsDocumented hypersensitivity; severe hepatic dysfunction
InteractionsDo not give with dairy products or with any divalent cations (eg, Fe++, Ca++, Mg++); can increase hypoprothrombinemic effects of anticoagulants (monitor PT in patients taking both medications); coadministration can decrease the pharmacologic effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsPhotosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider determining drug serum levels in prolonged therapy; doxycycline use during tooth development (last half of gestation through age 8 y) can cause permanent discoloration of teeth; fluids should be liberally consumed to reduce the risk of esophageal irritation and ulceration



Further Inpatient Care

  • If patients with pneumonia due to M pneumoniae require admission, use of standard and droplet precautions are recommended for the duration of the illness.

Further Outpatient Care

  • Antibiotic prophylaxis for exposed contacts is not routinely recommended. However, macrolide or doxycycline prophylaxis should be used in households in which patients with underlying conditions may be predisposed to severe mycoplasmal infection, such as those with sickle cell disease or antibody deficiencies.

Complications

  • Lobar consolidation
  • Abscess
  • Bronchiolitis obliterans
  • Necrotizing pneumonitis
  • Acute respiratory distress syndrome
  • Respiratory failure
  • Extremely rare extrapulmonary complications include the following: myocarditis, pericarditis, conduction abnormalities, encephalitis, Guillain-Barré syndrome, peripheral neuropathy, transverse myelitis, hemolytic anemia, coagulopathies, erythema multiforme, macular exanthems, vesicular exanthems, erythema nodosum, and urticaria.

Prognosis

  • With proper treatment, a full recovery is expected.



The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Santos Cantu Jr, MD, to the development and writing of this article.



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Pneumonia, Mycoplasma excerpt

Article Last Updated: Aug 5, 2008