para>Uncommonly isolated as a single agent in elderly patients
Pediatric Considerations
Unusual in infants and children <5 years; (pneumonia <5 years is more commonly viral)
Increased incidence of asthma exacerbation in older children
All infants 3 to 6 months with suspected bacterial pneumonia should be hospitalized.
EPIDEMIOLOGY
Incidence
- Estimated 1 million cases per year in the United States
- Responsible for 20% of community-acquired pneumonia (CAP) requiring hospitalizations annually
- Infection occurs most frequently in fall/winter seasons but may develop year round.
Prevalence
- Predominant sex: male = female
- Predominant age group affected: 5 to 20 years
- May occur at any age
- Rare in children <5 years of age
- Responsible for 15 " 20% of all cases of CAP yearly
- Most common cause of pneumonia in school children and young adults who do not have a chronic underlying condition
ETIOLOGY AND PATHOPHYSIOLOGY
- M. pneumoniae is a short-rod mucosal pathogen, which lacks a cell wall and thus not visible on Gram stain.
- Can grow under both aerobic and anaerobic conditions
- Highly contagious, M. pneumoniae is transmitted by contact and aerosols.
- Pathogenicity linked to its filamentous tips, which adhere selectively to respiratory epithelial cell membrane proteins with production of H2O2 and superoxide radicals, damaging cilia
- Many pathogenic features of infection are believed to be immune-mediated, not directly induced.
- Decreased ciliary movement produces prolonged paroxysmal, hacking cough.
ALERT
Macrolide-resistant M. pneumoniae has emerged in cases of adult CAP and pediatric pneumonias in Asia, France, Italy, Israel, and the United States.
Infection by M. pneumoniae has come to be recognized as a worldwide cause of CAP.
M. pneumonia infection may worsen asthma symptoms as well as cause wheezing in children without asthma.
RISK FACTORS
- Immunocompromised state (e.g., HIV, transplant recipients, chemotherapy)
- Smoking
- Close community living (e.g., military bases, prisons, hospitals, fraternity houses, schools, household contacts)
GENERAL PREVENTION
Consider droplet isolation of active cases.
COMMONLY ASSOCIATED CONDITIONS
- Asthma exacerbations as a result of proinflammatory cytokine release
- Chronic obstructive pulmonary disease
DIAGNOSIS
HISTORY
- Infection may be asymptomatic.
- Gradual onset of headache, malaise, low-grade fevers, chills
- Symptoms of upper respiratory infection then occur, including incessant, nonproductive, worsening cough (which may become mildly productive late in the disease); rhinorrhea, pharyngitis, and sinusitis (1)[A]
- Pneumonia may occur with associated pleural effusion; however, dyspnea is rare.
- The presence of pleuritic chest pain warrants a higher suspicion of M. pneumoniae. (1)[A]
- Extrapulmonary findings may develop in 5 " 10% of patients, including arthralgias, skin rashes, cervical adenopathy, hemolysis, congestive heart failure (CHF), and cardiac conduction abnormalities.
- Neurologic symptoms develop more commonly in children and may include encephalitis, aseptic meningitis, cranial nerve palsies, cerebellar ataxia, ascending paralysis, and coma (2)[C].
- Persistent cough is common during convalescence; other sequelae are rare.
PHYSICAL EXAM
- Patients generally appear nontoxic.
- Hacking/pertussis-like cough may be present along with fever and lassitude.
- Normal lung findings with early infection, but rhonchi, rales, and/or wheezes may develop several days later. (1)[A]
- Mild pharyngeal injection without exudates
- Minimal/no cervical adenopathy
- Erythematous tympanic membranes or bullous myringitis in patients >2 years of age is an uncommon but unique sign.
- Some patients may develop a pleural friction rub.
- Various exanthems, including erythema multiforme and Stevens-Johnson syndrome
DIFFERENTIAL DIAGNOSIS
- Viral/bacterial/fungal pneumonia
- Tuberculosis
- Other atypical pneumonias, including Chlamydia pneumoniae, Chlamydophila psittaci, Coxiella burnetii (Q fever), Francisella tularensis (tularemia), Pneumocystis jiroveci, Legionella pneumophila
DIAGNOSTIC TESTS & INTERPRETATION
- Microbial diagnosis is uncommon in outpatients as empiric treatment usually successful.
- PCR is the diagnostic test of choice, when available.
- No clinical or radiographical findings can differentiate between M. pneumoniae and other atypical pneumonia pathogens (Chlamydia/Legionella).
Initial Tests (lab, imaging)
- WBC count may be normal or elevated.
- Hemolytic anemia has been described but is rare.
- Elevated erythrocyte sedimentation rate (ESR) may be present but is nonspecific.
- When available, polymerase chain reaction (PCR) for M. pneumoniae DNA in respiratory secretions, CSF, and tissue samples may be the most sensitive and specific
- CXR shows reticulonodular pattern with patchy areas of lower lobe consolidation, although this is not specific. Small pleural effusion may be present in 10 " 15% cases.
Follow-Up Tests & Special Considerations
- Sputum Gram stains are not helpful because M. pneumoniae lacks a cell wall and cannot be stained.
- M. pneumoniae is difficult to culture and requires 7 to 21 days to grow; culturing is successful in 40 " 90% of cases but does not provide information to guide treatment, thus infrequently performed.
- Complement fixation serologic assay shows 4-fold rise in IgM antibody titer at 2 to 4 weeks after symptom onset; this is an older technique.
- Positive cold agglutinins (titer of ≥1:128 or rising 4-fold) in 50% of infections but can take 1 to 2 weeks to develop; not sensitive/specific; not routinely recommended
- CT of chest may show a combination of patchy tree-in-bud opacities with segmental ground glass opacities.
TREATMENT
GENERAL MEASURES
- Avoid sick contacts.
- Treatment is usually empiric and must be comprehensive to cover all likely pathogens in the context of the clinical setting.
- Calculation of pneumonia severity score (CAP score: www.mdcalc.com/psi-port-score-pneumonia-severity-index-adult-cap) may be helpful in determining inpatient versus outpatient treatment.
ALERT
There is insufficient evidence regarding the efficacy of antibiotics in pediatric patients infected with M. pneumoniae. However, some studies show benefit to treating with a macrolide and amoxicillin to cover M. pneumoniae in addition to other likely agents causing CAP (3,4)[A].
Pregnancy Considerations
Azithromycin: pregnancy Category B (preferred treatment)
Clarithromycin, levofloxacin, and moxifloxacin: pregnancy Category C
Doxycycline: pregnancy Category D
MEDICATION
First Line
- Azithromycin
- <3 months of age: not established
- >3 months of age: day 1, 10 mg/kg PO 1 (not to exceed 500 mg); days 2 to 5: 5 mg/kg PO daily (not to exceed 250 mg/day)
- Adults: 500 mg PO 1 followed by 250 mg PO daily 4 days (5)[A]
- Clarithromycin
- Children <6 months of age: not established
- Patients >6 months of age: 15 mg/kg/day PO divided q12h for 10 to 14 days
- Adults: 250 to 500 mg PO BID for 10 to 14 days
- Erythromycin
- Children: 20 to 50 mg/kg/day (base) PO divided q6 " 8h for 10 to 14 days
- Adults: 500 mg (base) PO q6h 10 to 14 days (5)[A],( 6)[B]
- Doxycycline
- Children <8 years of age: not recommended
- Children >8 years of age ( ≤45 kg): 2 to 4 mg/kg/day up to 200 mg/day PO divided BID for 10 to 14 days
- Children >8 years of age ( ≥ 45 kg): Refer to adult dosing.
- Adults: 100 mg PO BID 7 to 14 days (5)[A],( 6)[B]
- Useful in macrolide-resistant strains of M. pneumoniae.
Second Line
- Levofloxacin
- Children <18 years of age: not recommended
- Adults: 500 mg PO daily 7 to10 days (5)[A]
- Moxifloxacin
- Children <18 years of age: not recommended
- Adults: 400 mg/day PO for 7 to 10 days
- Levofloxacin and moxifloxacin show good activity against M. pneumoniae. Consider use with comorbid conditions and other pneumonia pathogens; also useful if macrolide resistance is suspected.
ADDITIONAL THERAPIES
- Albuterol inhaler: 2 puffs q4 " 6h as needed for wheezing
- Dexamethasone may downregulate cytokine release. (7)[B]
- Acetaminophen/ibuprofen as needed for fever
- Up to 10.9% of hospitalized patients may require mechanical ventilation.
- Plasmapheresis in cases of severe hemolytic anemia.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- CAP score risk class IV/V
- Advanced age with comorbidities
- Complicating neoplastic disease
- Significant cerebrovascular, cardiac, renal, liver, or GI symptoms
- Altered mental status
- Inability to maintain oxygen saturation
- Tachycardia/tachypnea
- Hypotension
- Neurologic symptoms
- Signs of Stevens-Johnson syndrome
- Significant hemolysis (autoimmune hemolytic anemia, cold agglutinin disease)
Discharge Criteria
- Change from IV to PO antibiotic may be made when:
- Respiratory distress and hypoxia have resolved.
- Patients are tolerating oral hydration.
- No significant complications are present.
- Generally, no need for 24-hour observation on PO antibiotics prior to discharge.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Clearing of condition on CXR should be documented in patients >50 years of age. (4)[A]
- In smokers, document a clear CXR in 6 to 8 weeks.
- Worsening symptoms/development of rash or meningeal/neurologic signs should prompt immediate presentation to medical attention.
- Antibiotic prophylaxis for exposed contacts is not routinely recommended.
- For household contacts who may be predisposed to severe mycoplasmal infection, macrolide or doxycycline prophylaxis should be used.
DIET
- No special diet considerations
- Ensure adequate hydration.
PATIENT EDUCATION
- Smoking cessation
- Contact and droplet precautions
- Adequate handwashing techniques
PROGNOSIS
- Symptoms usually resolve in 2 weeks.
- Some constitutional symptoms may persist for several weeks.
- With correct therapy, even most severe cases can expect complete recovery.
COMPLICATIONS
- All complications are rare, except reactive airway disease, hemolytic anemia, and erythema multiforme.
- Reactive airway disease may persist indefinitely and can cause acute chest syndrome in patients with sickle cell anemia.
- Meningoencephalitis
- Aseptic meningitis
- Peripheral neuropathy
- Transverse myelitis/acute transverse myelitis
- Cerebellar ataxia
- Acute disseminated encephalomyelitis
- Guillain-Barre syndrome
- Encephalitis (especially in children)
- Polyneuritis/polyarthritis
- Stevens-Johnson syndrome
- Pericarditis/myocarditis
- Respiratory distress syndrome
- Cerebral ataxia
- Thromboembolic phenomena
- Pleural effusion
- Nephritis
- Occasional deaths occur primarily among the elderly and persons with sickle cell disease.
REFERENCES
11 Wang K, Gill P, Perera R, et al. Clinical symptoms and signs for the diagnosis of Mycoplasma pneumoniae in children and adolescents with community-acquired pneumonia. Cochrane Database Syst Rev. 2012;(10):CD009175.22 Meyer Sauteur PM, Jacobs BC, Spuesens EB, et al. Antibody responses to Mycoplasma pneumoniae: role in pathogenesis and diagnosis of encephalitis. PLoS Pathog. 2014;10(6):e1003983.33 Mulholland S, Gavranich JB, Gillies MB, et al. Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children. Cochrane Database Syst Rev. 2012;(9):CD004875.44 Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25 " e76.55 Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; (44 Suppl 2):S27 " S72.66 Spindler C, Str ₯lin K, Eriksson L, et al. Swedish guidelines on the management of community-acquired pneumonia in immunocompetent adults " Swedish Society of Infectious Diseases 2012. Scand J Infect Dis. 2012;44(12):885 " 902.77 Remmelts HHE, Meijvis SCA, Biesma DH, et al. Dexamethasone downregulates the systemic cytokine response in patients with community-acquired pneumonia. Clin Vaccine Immunol. 2012;19(9):1532 " 1538.
ADDITIONAL READING
- Atkinson TP, Balish MF, Waites KB. Epidemiology, clinical manifestations, pathogenesis and laboratory detection of Mycoplasma pneumoniae infections. FEMS Microbiol Rev. 2008;32(6):956 " 973.
- Carbonara S, Monno L, Longo B, et al. Community-acquired pneumonia. Curr Opin Pulm Med. 2009;15(3):261 " 273.
- Chien S, Wells TG, Blumer JL, et al. Levofloxacin pharmacokinetics in children. J Clin Pharmacol. 2005;45(2):153 " 160.
- Eliakim-Raz N, Robenshtok E, Shefet D, et al. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev. 2012;(9):CD004418.
- Kashyap S, Sarkar M. Mycoplasma pneumonia: clinical features and management. Lung India. 2010;27(2):75 " 85.
- Torres A, Blasi F, Peetermans WE, et al. The aetiology and antibiotic management of community-acquired pneumonia in adults in Europe: a literature review. Eur J Clin Microbiol Infect Dis. 2014;33(7):1065 " 1079.
CODES
ICD10
J15.7 Pneumonia due to Mycoplasma pneumoniae
ICD9
483.0 Pneumonia due to mycoplasma pneumoniae
SNOMED
46970008 Pneumonia due to Mycoplasma pneumoniae (disorder)
CLINICAL PEARLS
- Most common atypical respiratory pathogens include M. pneumoniae, C. pneumoniae, and L. pneumophila.
- Atypical pneumonia is typically a clinical diagnosis; if labs are indicated, PCR is the mainstay of diagnosis with serology if PCR is not available.
- Watch closely for complicating symptoms that could indicate worsening disease.
- Atypical pneumonia with M. pneumoniae is typically self-limiting, difficult to identify, and usually responds to empiric treatment.
- Outbreaks of M. pneumoniae can be seen in close communities of young people.
- Onset of infection is typically have a gradual onset of symptoms, normal WBC, and less respiratory distress.