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Chlamydophila Pneumoniae
Fozia Akhtar Ali, MD
Teny Anna Philip, MD
image BASICS
  • Chlamydophila pneumoniae (formerly known as Chlamydia pneumoniae) is an obligate intracellular gram-negative bacterium causing atypical pneumonia or bronchitis in adolescents and young adults (1).
  • Associated with a more severe, persistent, latent infection in older adults
  • Humans are the only known reservoir.
  • Responsible for 10-20% of community-acquired pneumonia (CAP) among adults, 2nd to mycoplasma in cases of atypical pneumonia (1)
  • Epidemiologic studies suggest 4-year peaks.
  • The incubation period is ˜3 to 4 weeks.
  • Most infected persons are asymptomatic.
  • Typically presents as mild upper respiratory infection (URI). Bronchitis and pneumonia may follow in 1 to 4 weeks.
  • Primary infection more common in ages 7 to 40 years; reinfection pneumonia more common in elderly
  • Serologic evidence of previous infection is found in 50% of adults and 75% of elderly.
  • Male > female (60-90%); possibly due to smoking
  • Outbreaks have occurred among military recruits, university students, and nursing home residents, with incidence highest in elderly.
  • The overall incidence is unknown. Each year, an estimated 2 to 5 million cases of pneumonia (all causes) and 500,000 pneumonia-related hospitalizations occur in the United States (2).
10-20% of CAP cases among adults
  • The elementary body is the infectious form.
    • Rigid cell wall and relative metabolic inactivity allows the orgamism to survive outside of the host cell for a limited time.
  • The elementary body infects the host cell by receptor-mediated endocytosis and becomes a reticulate body (3).
  • Reticulate bodies divide intracellularly, forming intracytoplasmic inclusions that divide and release chlamydial antigens. This elicits a host immune response leading to mucus production in the nasal passages, sinuses, bronchial tree, and alveoli, along with nasopharyngeal and airway inflammation and bronchospasm.
  • After 48 to 72 hours, the reticulate bodies become elementary bodies and are released by cell lysis.
  • Close quarters—classrooms, military barracks, shelters, and nursing homes.
  • All ages at risk, but most common in school-age children. In the United States, 50% of adults have evidence of past infection by age 20. Reinfection throughout life appears to be common (2).
  • Transmission is by respiratory droplets. Hand washing and avoiding exposure to infected persons are key preventive steps.
  • Incidence high among military recruits during basic training; weekly azithromycin prophylaxis reduces case rate.
  • Chronic obstructive pulmonary disease
  • Asthma
  • HIV infection
  • Cystic fibrosis
  • Diabetes mellitus
  • General appearance usually nontoxic
  • Fever
  • Tachypnea
  • Tachycardia
  • Crackles or wheezing
  • Bronchial breath sounds
  • Percussion dullness and egophony less sensitive but more specific for pneumonia
  • Pharyngeal erythema without exudate
  • Other causes of atypical pneumonia, including Mycoplasma pneumoniae and Legionella pneumophila
  • Other bacterial causes of pneumonia, including S. pneumoniae, H. influenzae, Moraxella catarrhalis, and Staphylococcus aureus
  • Respiratory viruses: adenovirus, influenza A, influenza B, parainfluenza virus, and respiratory syncytial virus
  • Endemic fungal pathogens: coccidioidomycosis, histoplasmosis
  • Opportunistic fungal pathogens: Candida species, Aspergillus species, Mucor species, Cryptococcus neoformans
  • Other: psittacosis, Q fever, TB, tularemia
  • Conditions that mimic CAP: acute respiratory disease syndrome, idiopathic pulmonary fibrosis, neoplasm, pulmonary embolus, sarcoidosis, congestive heart failure
Initial Tests (lab, imaging)
  • Microimmunofluorescence (MIF) test is most commonly used (and most practical) initial test.
    • Sensitivity of 50-90% if using paired sera
    • IgM 1:16 or higher
    • IgG 1:512 or higher
    • IgM may not be detectable early in the disease.
  • Culture with oropharyngeal swab is the gold standard diagnostic method (not widely available).
    • Specificity 100%; sensitivity 50-70% (4)
    • Specimen should be kept cool and transported in specific media.
    • Most easily cultured using HL or HEp2 cells (5)
  • PCR from pharyngeal swab or bronchioalveolar lavage specimen (30-95% sensitivity, >95% specificity) (4); during an outbreak, one study showed PCR was less sensitive (68% vs. 79%) but more specific (93% vs. 86%) than MIF IgM (6).
  • White blood count is usually normal.
  • Alkaline phosphatase levels may be elevated.
  • Blood cultures are recommended if patient is toxic and requires ICU admission; otherwise less helpful.
  • Complement fixation for Chlamydia is available but cannot distinguish C. pneumoniae from Chlamydophila psittaci.
  • Chest x-ray (CXR) (7)[A] has no characteristic radiograph findings; CXR most commonly shows a single subsegmental infiltrate in the lower lobes.
  • Pleural effusion seen in 20-25% of cases. ARDS is rare.
  • Histologically, intra-alveolar inflammation with mild interstitial reaction is characteristic of chlamydial pneumonias. Alveolar lining cells contain intracytoplasmic inclusions.

Diagnostic Procedures/Other
Although serology is 95% specific, definitive diagnosis requires a positive culture or PCR testing.
Empiric coverage of atypical pathogens in patients with CAP has shown mortality benefit (8)[A].
First Line
Tetracyclines and macrolides are first choice (2).
  • Doxycycline: 100 mg PO BID for 10 to 14 days (may use IV in inpatient setting) OR
  • Azithromycin: 500 mg on day 1, then 250 mg on days 2 to 5 OR
  • Clarithromycin: 500 mg q12h for 10 to 14 days OR
  • Tetracycline: 500 mg PO QID for 10 to 14 days
    • Tetracyclines not for use during pregnancy or in children <8 years
    • Tetracyclines may cause photosensitivity; sunscreen is recommended.
Second Line
Alternative drugs
  • Levofloxacin: 250 to 500 mg/day (PO or IV) or other respiratory fluoroquinolones have good bioavailability and the convenience of once-daily dosing but are recommended for use only when patients have failed treatment with a 1st-line drug, have had recent antibiotics, significant comorbidities, or have allergies to 1st-line medications.
Pregnancy Considerations
Avoid tetracyclines in pregnant women.
  • Usually outpatient care. Those with severe pneumonia or coexisting illness may require hospitalization.
  • Pneumonia severity index can help predict morbidity and need for hospitalization (7).
Admission Criteria/Initial Stabilization
Infection in debilitated or hospitalized patients can be severe; ventilatory support for respiratory failure
Discharge Criteria
Reversal of respiratory distress, tolerating PO medications, otherwise stable medically, and clinically stable for discharge
Patient Monitoring
  • Monitor patients weekly until well.
  • Follow-up CXR can document resolution.
  • Reinfection is possible.
  • Pneumonia is more likely to be life-threatening in older adults and patients with other underlying pulmonary disease (e.g., asthma, chronic obstructive pulmonary disease [COPD]) or the immune compromise (e.g., diabetes), with an overall 0.5-29% mortality rate.
  • Death usually from secondary infection or underlying comorbidity
1. Blasi F, Tarsia P, Aliberti S. Chlamydophila pneumoniae. Clin Microbiol Infect. 2009;15(1):29-35.
2. Centers for Disease Control and Prevention. Chlamydophila pneumoniae infection. http://www.cdc.gov/pneumonia/atypical/chlamydophila.html. Accessed 2014.
3. Thibodeau KP, Viera AJ. Atypical pathogens and challenges in community-acquired pneumonia. Am Fam Physician. 2004;69(7):1699-1706.
4. Kumar S, Hammerschlag MR. Acute respiratory infection due to Chlamydia pneumoniae: current status of diagnostic methods. Clin Infect Dis. 2007;44(4):568-576.
5. Burillo A, Bouza E. Chlamydophila pneumoniae. Infect Dis Clin North Am. 2010;24(1):61-71.
6. Hvidsten D, Halvorsen DS, Berdal BP, et al. Chlamydophila pneumoniae diagnostics: importance of methodology in relation to timing of sampling. Clin Microbiol Infect. 2009;15(1):42-49.
7. Lutfiyya MN, Henley E, Chang LF, et al. Diagnosis and treatment of community-acquired pneumonia. Am Fam Physician. 2006;73(3):442-450.
8. Shefet D, Robenshtock E, Paul M, et al. Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev. 2005;(2):CD004418.
9. Zhan P, Suo LJ, Qian Q, et al. Chlamydia pneumoniae infection and lung cancer risk: a metaanalysis. Eur J Cancer. 2011;47(5):742-747.
Additional Reading
Conklin L, Adjemian J, Loo J, et al. Investigation of a Chlamydia pneumoniae outbreak in a federal correctional facility in Texas. Clin Infect Dis. 2013; 57(5):639-647.
J16.0 Chlamydial pneumonia
Clinical Pearls
  • Consider C. pneumoniae in well-appearing young patients presenting with CAP.
  • Culture is the gold standard for diagnosis of C. pneumoniae. Serodiagnosis is used for acute infection.
  • Tetracyclines or macrolides are initial drugs of choice.