AUTHOR INFORMATION

Section 1 of 10

Authored by Santos Cantu, Jr, MD, Consulting Staff, Department of Pediatrics, Christus Santa Rosa Children's Hospital

Edited by 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, Program Director, Department of Emergency Medicine, Maricopa Medical Center; Assistant Professor, Department of Surgery, University of Arizona; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Robert E O'Connor, MD, MPH, Director of Education and Research, Department of Emergency Medicine, Christiana Care Health System; Professor of Emergency Medicine, Thomas Jefferson University

Author's Email:	Santos Cantu, Jr, MD
Editor's Email:	Joseph A Salomone III, MD

eMedicine Journal, February 26 2006, VOLUME 7, Number 2

INTRODUCTION

Section 2 of 10

Background: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, and the disease usually is of gradual onset. In 1938, Reimann probably described the first cases of mycoplasmal pneumonia. Reimann coined the term "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; this discovery later led to the work of Eaton who is credited with discovering, in 1944, a specific agent (at the time he thought it was a virus) as the principal cause of primary atypical pneumonia.

Pathophysiology: The responsible organism, M pneumoniae, is a pleomorphic organism that lacks a cell wall. The prolonged paroxysmal cough seen in this disease is thought to be due to the inhibition of ciliary movement, since the organism has a filamentous end that allows it to slip between cilia within the respiratory epithelium.

The organism has 2 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.

More recently, much of the pathogenicity of M pneumoniae has been attributed to the activation of inflammatory mediators, including cytokines. In fact, one study noted decreased concentrations of M pneumoniae in the lung of a mouse model after the use of inhaled corticosteroids.

Frequency:

• In the US: Infections with M pneumoniae result in pneumonia in only 3% of cases; 20% of infections are asymptomatic, while 77% involve the upper respiratory tract. Although mycoplasmal pneumonia can occur at any time of the year, outbreaks tend to occur in the fall. The incubation period 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.

Mortality/Morbidity: In almost all patients, the pneumonia resolves without any serious complications.

Sex: The incidence is higher in males than females.

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 4 years.

CLINICAL

Section 3 of 10

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

• Worsening dry cough

• Headache

• Chilliness, 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

• Mild pharyngeal erythema with minimal or no cervical adenopathy but no exudate

• Normal findings with early infection but rhonchi, rales, and/or wheezes several days later

• Various exanthems including Stevens-Johnson syndrome

Causes:

• The causative agent is M pneumoniae, which belongs to the class Mollicutes, the smallest known free-living microorganisms.

• M pneumoniae is difficult to culture and requires 7-21 days to grow; culturing is successful in only 40-90% of cases.

• 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.

DIFFERENTIALS

Section 4 of 10

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)

WORKUP

Section 5 of 10

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, except in excluding other pathogens.

• Elevated erythrocyte sedimentation rates may be present.

Imaging Studies:

• Radiographic findings are variable, but 4 distinct patterns have been described frequently in mycoplasmal pneumonia.

• 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.

• Nodular infiltration may resemble that associated with other diseases with granulomatous pathology, such as tuberculosis, mycoses, and sarcoidosis.

• Hilar adenopathy sometimes is mistaken for malignancy.

• Pleural effusions can be seen rarely on lateral decubitus films.

• High-resolution CT scans have been shown in small series to be more sensitive than chest radiography in demonstrating lung disease.

Other Tests:

• 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. 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.

• A radiolabeled DNA probe detects M pneumoniae ribosomal RNA in respiratory secretions with 90% sensitivity.

TREATMENT

Section 6 of 10

Emergency Department Care: In general, mycoplasmal pneumonia is a diagnosis that does not need emergency treatment. However, various pulmonary and extrapulmonary complications may occur and may require emergent attention.

MEDICATION

Section 7 of 10

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 Name	Erythromycin (EES, Erythrocin, E-mycin) -- Inhibits 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 Dose	500 mg PO qid for 7-10 d
Pediatric Dose	7.5-12.5 mg/kg/dose PO qid for 7-10 d
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution 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 Name	Azithromycin (Zithromax) -- One of the newer macrolides; very effective against M pneumoniae. Perhaps the most common agent used to treat M pneumoniae given its ease of administration.
Adult Dose	Day 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
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May 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
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Site 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 Name	Clarithromycin (Biaxin) -- Reversibly 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 Dose	250 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
Contraindications	Documented hypersensitivity; coadministration of pimozide
Interactions	Toxicity 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
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration 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 Name	Tetracycline (Sumycin) -- Treats susceptible bacterial infections of both gram-positive and gram-negative organisms, as well as infections caused by Mycoplasma, Chlamydia, 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 Dose	500 mg PO bid for 1-4 wk
Pediatric Dose	<8 years: Not recommended >8 years: 10-20 mg/lb (25-50 mg/kg) PO divided bid/qid
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Do 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
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider determining drug serum levels in prolonged therapy; tetracycline use during tooth development (last half of gestation through age 8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines

FOLLOW-UP

Section 8 of 10

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 tetracycline prophylaxis should be used in households in which patients with underlying conditions may be predisposed to severe mycoplasmal infection (eg, 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: pericarditis, arthritis, Stevens-Johnson syndrome, hemolytic anemia, thrombocytopenia, CNS infections, Guillain-Barré syndrome, peripheral neuropathy, other neurologic manifestations, and ocular complications. Recently, an association has been proposed between M pneumoniae infection and Tourette syndrome, but this association has not been extensively studied.

Prognosis:

• With proper treatment, a full recovery is expected.

TEST QUESTIONS

Section 9 of 10

CME Question 1: A 16-year-old male adolescent comes to the ED with a 2-week history of dry cough and shortness of breath. The ED physician suspects infection with Mycoplasma pneumoniae infection. Which of the following other historical findings is least likely to be present in this patient?

A: Sore throat
B: Fever
C: Malaise
D: Joint symptoms
E: Headache

The correct answer is D: Infection with Mycoplasma pneumoniae can cause a myriad of symptoms including fever, malaise, dry cough, headache, sore throat, and chills. Joint symptoms can occur but are not as frequent as the other symptoms.

CME Question 2: A 16-year-old male adolescent comes to the ED with a 2-week history of dry cough and shortness of breath. The ED physician suspects Mycoplasma pneumoniae infection. Which of the following physical findings is the ED physician likely to discover?

A: Generally ill appearance
B: Clear oropharynx
C: Bullous myringitis
D: Petechial rash
E: Cervical lymphadenopathy

The correct answer is C: Patients with mycoplasmal pneumonia are likely to have abnormal lung findings, although rales, rhonchi, and/or wheezing may not be heard with early infection. The patient has had symptoms for 2 weeks and, thus, is likely to have positive lung findings on auscultation. Patients with mycoplasmal pneumonia are not ill appearing and are likely to have a mildly erythematous oropharynx without cervical lymphadenopathy. Bullous myringitis is a finding that occasionally can be noted on examination. A rash can be seen in the occasional patient with mycoplasmal pneumonia, but it is not petechial.

Pearl Question 1 (T/F): The ratio of males to females who become infected with Mycoplasma pneumoniae is 2:1.

The correct answer is False: The sex distribution is equal in this illness.

Pearl Question 2 (T/F): Persons aged 4-20 years are those most commonly affected with pneumonia secondary to Mycoplasma pneumoniae infection.

The correct answer is True: Pneumonia from Mycoplasma pneumoniae infection is most common in persons aged 4-20 years. Illness does occur in younger and older patients, but it occurs more commonly in the first 2 decades of life.

Pearl Question 3 (T/F): The antimicrobial of choice in treatment of mycoplasmal pneumonia is a macrolide.

The correct answer is True: Macrolides (erythromycin, azithromycin, or clarithromycin) are the drug of choice for the treatment of Mycoplasma pneumoniae infections.

Pearl Question 4 (T/F): Common radiographic findings in patients with mycoplasmal pneumonia include platelike atelectasis, nodular infiltration, and hilar adenopathy.

The correct answer is True: On radiographs, bronchopneumonia from mycoplasmal pneumonia often is seen as platelike atelectasis, nodular infiltration, and hilar adenopathy. Bronchopneumonia often involves a single lower lobe. Lobar consolidation is rare.

BIBLIOGRAPHY

Section 10 of 10

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• Reimann HA: An acute infection of the respiratory tract with atypical pneumonia: a disease entity probably caused by a filtrable virus. JAMA 1938; 111: 2377-2384.
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