AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The genus Chlamydia includes 3 species that are pathogenic to humans: Chlamydia pneumoniae, Chlamydia psittaci, and Chlamydia trachomatis. These are small, gram-negative, obligate intracellular organisms. All 3 species can cause pneumonia in humans.

C pneumoniae causes mild pneumonia or bronchitis in adolescents and young adults. Older adults may experience more severe disease and repeated infections.

C psittaci causes psittacosis or ornithosis after exposure to infected birds. Ornithosis is the preferred term, since almost any bird except psittacine birds (eg, parakeets, parrots) can transmit the organism. The clinical spectrum of C psittaci infection ranges from an asymptomatic infection to a fulminant toxic syndrome. Patients with ornithosis most commonly present with pneumonia or fever of unknown origin.

C trachomatis is an important cause of sexually transmitted diseases, including trachoma, pelvic inflammatory disease, and cervicitis. C trachomatis can also cause pneumonia, primarily in infants and young children. Reports document cases of pneumonia due to C trachomatis in immunocompromised adults and laboratory workers.

Pathophysiology

Chlamydiae initiate infection by attaching to the outer membrane of the susceptible host cells. The organism subsequently produces cytoplasmic inclusions in infected cells. The cells release the matured inclusions to infect adjacent cells.

The mode of transmission is different for the 3 species, but all can cause systemic disease by hematogenous spread. Respiratory secretions transmit C pneumoniae from human to human, whereas infected birds transmit C psittaci to humans via the respiratory route through direct contact or aerosolization. Birds known to cause ornithosis include parrots, parakeets, chickens, ducks, turkeys, pigeons, and sparrows, among others.

When pregnant women have a C trachomatis infection of the cervix, the organism is transmitted when the infant passes through the infected birth canal. C trachomatis infection may cause neonatal conjunctivitis, nasopharyngitis, otitis media, and pneumonitis. The tendency to chronic inflammation is typical, and chronic persistent infection may occur if neonatal infections remain untreated.

Frequency

United States

• C pneumoniae: Approximately 50% of young adults and 75% of elderly persons have serological evidence of previous infection. The pathogen is estimated to cause 3-10% of community-acquired pneumonia cases among adults. The estimated number of cases of C pneumoniae pneumonia is 300,000 cases per year. Although C pneumoniae infections occur every year, epidemiological studies suggest a 4-year cycle in the incidence of C pneumoniae pneumonia.
• C psittaci: Cases of ornithosis declined after the introduction of antibiotic-laced bird feed and a quarantine period of 30 days for imported birds. From 1987-1996, 619 cases of psittacosis in humans were reported to the US Centers for Disease Control and Prevention (CDC), which is approximately 50-100 cases per year. Since 1996, fewer than 50 confirmed cases have been reported in the United States each year. The diagnosis of psittacosis can be difficult, and many more cases may occur that are not correctly diagnosed or reported.
• C trachomatis: In infants, an estimated 12,000 cases of pneumonia due to C trachomatis occur each year. Approximately 5-22% of pregnant women are thought to have C trachomatis infection of the cervix, and 30-50% of neonates born to infected mothers show culture evidence of infection. Of infected neonates, 15-25% present with clinical conjunctivitis and nasopharyngitis that in some cases develops into neonatal pneumonitis.

Mortality/Morbidity

• The mortality rate from infection with C psittaci was 20% in the preantibiotic era. The mortality rate is 5% with antibiotic treatment; it is less than 1% with early diagnosis and treatment.
• The mortality rate from C pneumoniae infection was 9% in a meta-analysis. Mixed infection with other bacteria (eg, pneumococci) or the presence of severe underlying disease increased the mortality risk.
• Most patients with C trachomatis infant pneumonia are only moderately ill; if the infection is not treated, respiratory failure and prolonged spells of apnea may occur.

Sex

• C pneumoniae is more common in males (60-90%) than in females; this difference is possibly due to cigarette smoking.

Age

• Anyone exposed to infected birds is at risk for infection with C psittaci.
• The incidence of C pneumoniae pneumonia is highest among elderly persons. Primary infection pneumonia is more common in persons aged 7-40 years, whereas reinfection pneumonia is more common in elderly persons.
• With regard to C trachomatis pneumonia, approximately 11-20% of infants born to infected mothers develop symptomatic pneumonia before age 8 weeks. Adult cases have been reported in immunocompromised hosts.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• C psittaci
• • Exposure to birds, especially sick birds, is a clue to the diagnosis in a patient with pneumonia and splenomegaly. Pet shop employees and poultry industry workers are at risk. Obtain an occupational and avocational history in all patients with community-acquired pneumonia.
  • The incubation period is 5-14 days or longer. Abrupt onset of constitutional symptoms is a common presentation in symptomatic patients.
  • The severity of disease ranges from asymptomatic to severe pneumonia with systemic illness.
  • A nonproductive cough has been observed in 50-80% of patients; however, this symptom is often absent initially. Chest pain is common, but pleuritic pain is rare.
  • Fever is the most common symptom and may reach 103-105°F (39.4-40.5°). Some patients may present with culture-negative endocarditis or fever of unknown origin.
  • Signs of meningitis or encephalitis, including focal neurological deficits and seizures, may develop. Photophobia, epistaxis, tinnitus, deafness, GI symptoms, and arthralgia have been reported in less than half the patients.
• C pneumoniae
• • The incubation period is approximately 3-4 weeks. The onset is usually gradual and may be biphasic. Symptoms of bronchitis or pneumonia follow upper respiratory tract symptoms in 1-4 weeks.
  • Most persons with C pneumoniae infections are asymptomatic, and most have respiratory illnesses that are relatively mild.
  • Sputum is usually scant, but cough is prominent.
  • A history of hoarseness is more common in C pneumoniae infection than in mycoplasmal infection or other pneumonias.
  • Headache occurs in as many as 58% of cases and may be important as a nonclassic pneumonia finding.
  • Patients with C pneumoniae infection are less likely to report fever.
  • Symptoms may be prolonged, with persistent cough and malaise for weeks to months despite appropriate use of antibiotics.
• C trachomatis pneumonia
• • Nasal obstruction and discharge, cough, and tachypnea are present.
  • Infants are usually symptomatic for 3 weeks or more before presentation.

Physical

• C psittaci
• • A pulse-temperature dissociation; somnolence; splenomegaly; and an erythematous, blanching, maculopapular rash (eg, Horder spots) in the presence of pneumonia suggest ornithosis. Rose spots are observed in persons with typhoid fever and look very similar to Horder spots.
  • Auscultatory findings may be sparse and may underestimate the extent of pneumonia.
  • Defervescence is usually slow.
  • Signs of hepatitis, hemolytic anemia, disseminated intravascular coagulation, meningoencephalitis, or reactive arthritis may be observed.
  • Cutaneous manifestations, including Horder spots, splinter hemorrhages, superficial venous thromboses, acrocyanosis, and erythema nodosum, are observed.
• C pneumoniae
• • Fever is more often present in the first few days than in a week or later. Fever is often absent by the time of examination.
  • Pharyngeal erythema without exudate occurs in various atypical pneumonias; however, sinus percussion tenderness is more common with C pneumoniae pneumonia than with other pneumonias.
  • Rhonchi and rales are present even in mild disease.
• C trachomatis pneumonia
• • Most patients are afebrile and only moderately ill.
  • Scattered crackles with good breath sounds are characteristic. Wheezing is usually absent.
  • Conjunctivitis and middle ear abnormality are present in half the infants with pneumonia.

Causes

All 3 human pathogenic species, including C pneumoniae, C psittaci, and C trachomatis, may cause chlamydial pneumonia.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

C trachomatis infant pneumonia
Respiratory syncytial virus infection
Bordetella pertussis infection
Infection with other respiratory viruses

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• C psittaci
• • Single serum titers are insensitive and nonspecific. Confirmation with paired acute and convalescent sera is advised.
  • According to CDC case definitions, a confirmed case involves (1) isolation of the organism by culture, although culture is difficult and hazardous and serologic tests are preferred or (2) compatible clinical illness with a 4-fold rise in complement-fixing (CF) or microimmunofluorescence (MIF) antibodies to a reciprocal titer of 32 or greater by paired sera at least 2 weeks apart or detection of immunoglobulin M (IgM) antibody (>16) against C psittaci by MIF.
  • The CDC defines a probable case as a compatible clinical illness (1) that is epidemiologically linked to a confirmed case or (2) that has a single antibody titer of 32 or greater through MIF or CF after the onset of symptoms.
• C pneumoniae
• • A definite case of C pneumoniae infection occurs with a 4-fold rise in C pneumoniae–specific MIF antibody at 3-4 weeks. (Note: A CF test cross-reacts with C psittaci.)
  • A possible case occurs when C pneumoniae–specific MIF immunoglobulin G (IgG) is greater than or equal to 512 and IgM is greater than or equal to 32.
  • Single elevated IgG titers may not be reliable because elderly patients can have persistently elevated IgG titers because of repeated infections.
  • The absence of detectable antibodies several weeks after the onset of infection does not exclude a diagnosis of acute C pneumoniae pneumonia because the IgM antibody response may take as long as 6 weeks and the IgG antibody response may take as long as 8 weeks to appear in primary infections.
  • The white blood cell count is usually not elevated in C pneumoniae infection. Alkaline phosphate levels may be elevated.
  • In some laboratories, a polymerase chain reaction with pharyngeal swab, bronchoalveolar lavage, sputum, or tissue can be used to seek C pneumoniae–specific DNA. It is the most promising rapid test but is still experimental.
  • Cell culture with oropharyngeal swabs is probably the best test, but it requires specialized culture techniques. It is only performed in research laboratories.
• C trachomatis
• • Clinical findings suggest the diagnosis; the presence of chlamydial inclusions or elementary bodies on Giemsa-stained smears of the conjunctivae or nasopharynx confirms the diagnosis.
  • Testing may show findings of elevated antichlamydial IgM titer. Peripheral eosinophilia and elevated serum immunoglobulin results are characteristic.

Imaging Studies

• Chest radiographs
• • C psittaci: Consolidation in a single lower lobe is the most common finding. However, various findings have been observed, including patchy reticular infiltrates radiating from the hilum, a diffuse ground-glass appearance, or a miliary pattern. Pleural effusions are evident in as many as 50% of cases; however, the effusions are usually small and do not cause symptoms.
  • C pneumoniae: Chest radiographs most commonly show a single subsegmental infiltrate that is mainly located in the lower lobes. Extensive consolidation is rare, although acute respiratory distress syndrome has been reported. No radiographic findings are characteristic. Residual changes can be observed even after 3 months. Pleural effusion occurs in 20-25% of cases.
  • C trachomatis: Chest radiographs show bilateral interstitial infiltrates with hyperinflation.

Other Tests

• C pneumoniae: Rapid confirmation of the diagnosis with polymerase chain reaction testing is possible; however, this technique is not readily available.
• C trachomatis: Screen parents for chlamydia and other sexually transmitted diseases.

Histologic Findings

Intra-alveolar inflammation with a milder degree of interstitial reaction is a characteristic pathologic finding in the lungs. Alveolar-lining cells contain intracytoplasmic inclusions.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• C psittaci
• • Tetracycline or doxycycline is the treatment of choice. Continue treatment for 10-21 days. A longer course to prevent relapse is controversial.
  • Erythromycin is the alternative treatment, but this drug may be less efficacious in severe cases.
• C pneumoniae
• • Doxycycline is the treatment of choice except in children younger than 9 years and pregnant women. Treatment should be continued for at least 10-14 days after defervescence. If symptoms persist, a second course with a different class of antibiotics is usually effective.
  • In outpatient settings, use doxycycline (100 mg PO bid) or tetracycline hydrochloride (500 mg PO qid).
  • In inpatient settings, use doxycycline hyclate (100 mg IV bid).
  • Alternatives include erythromycin (500 mg PO/IV qid) and newer macrolides such as azithromycin (500 mg PO/IV qd for 7-10 d) and clarithromycin (1 g PO qd [Biaxin XL] or 500 mg PO bid for 10 d). Newer macrolides are better tolerated than erythromycin. Shorter courses of the newer macrolides appear to be effective.
  • Telithromycin is the first antibiotic in a new class called ketolides and is approved by the US Food and Drug Administration for C pneumoniae pneumonia. It is more expensive than doxycycline. Telithromycin is a potent inhibitor of CYP3A4 and can cause potentially dangerous increases in serum concentrations of simvastatin, lovastatin, atorvastatin, midazolam, and other drugs. If telithromycin is used, statins should be withheld for the duration of therapy. Hepatotoxicity (some fatal cases) has also been reported.
  • Fluoroquinolones, including levofloxacin (500 mg PO/IV qd for 10-14 d) and moxifloxacin (400 mg PO/IV qd for 10-14 d), also have some activity, although less than that of tetracyclines or macrolides. Gatifloxacin is no longer marked in the United States.
• C trachomatis infant pneumonia
• • Treatment for infant pneumonia mirrors the treatment for conjunctivitis. The efficacy is approximately 80-90%.
  • Treat with erythromycin (50 mg/kg/d PO divided q6h for 10-14 d).
  • Doxycycline is contraindicated in children younger than 9 years.

Surgical Care

Valve replacement may be required for patients with endocarditis.

Consultations

• C psittaci: Patients may require consultation with infectious disease and pulmonary specialists. In most states, physicians are required to report cases of psittacosis to the appropriate health authorities.
• C pneumoniae: Consultations with infectious disease and pulmonary specialists may be required if a patient needs hospitalization or does not respond to therapy.
• C trachomatis: Mothers of infected children may need consultations with ophthalmologists and sexually transmitted disease specialists.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate infection, to reduce morbidity, and to prevent complications.

Drug Category: Antibiotics

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

Tetracyclines and macrolides are the drugs of choice for this indication. Tetracyclines are bacteriostatic in nature; they work by inhibiting protein synthesis. As a class, tetracyclines have similar antimicrobial profiles, and cross-resistance is likely. Macrolides inhibit bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, thus causing cessation of RNA-dependent protein synthesis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• C psittaci: Valve replacement and prolonged antibiotic treatment may be necessary for patients with endocarditis.
• C pneumoniae: Treat mixed infections with other organisms (eg, pneumococci, mycoplasmata, legionellae) when present. The frequency of mixed infection can be as high as 66%.

Further Outpatient Care

• C psittaci: A full recovery usually takes 6-8 weeks, and relapse may occur.
• C pneumoniae: Treatment failure may occur more often with erythromycin. Re-treatment is often successful, especially with tetracyclines. Complete recovery is slow. Cough and malaise may persist for weeks to months despite appropriate treatment.
• C trachomatis: A higher-than-normal incidence of obstructive airway disease or asthma occurs in children who had chlamydial pneumonia before age 6 months.

Transfer

• Severely ill hypoxemic patients require ventilatory support in the ICU.

Deterrence/Prevention

• C psittaci
• • Avoid dust from bird feathers and cage contents. Do not handle sick birds.
  • Imported psittacine birds must be treated for 45 days with a balanced feed containing chlortetracycline with 0.7% calcium.
  • Refer infected birds or suspected sources to veterinarians.
  • Past infection with C psittaci does not confer immunity to the disease.
• C pneumoniae: The incidence of infection among military recruits during basic training is high, and weekly azithromycin prophylaxis was 58% effective in preventing the disease in this setting.
• C trachomatis
• • Evaluate mothers of infected children and their sexual partners, and treat them appropriately.
  • Repeated parental screening may be warranted in high-risk populations.

Complications

• C psittaci: Complications include endocarditis, thrombophlebitis, myocarditis, thyroiditis, pancreatitis, hepatitis, renal failure, disseminated intravascular coagulation, and fetal death in infected pregnant women.
• C pneumoniae
• • Complications include sinusitis, otitis, reactive arthritis, erythema nodosum–type vasculitis, myocarditis, and endocarditis.
  • New-onset asthma has been observed after C pneumoniae infection.
  • While some studies clearly associate C pneumoniae organisms with atheromatous plaques or sarcoidosis, the role of C pneumoniae in the pathogenesis of these syndromes remains to be established. Antibiotic trials for coronary artery disease are not supportive of their role.
• C trachomatis: Complications include neonatal inclusion conjunctivitis, meningoencephalitis, myocarditis, and endocarditis.

Prognosis

• C psittaci infection is usually curable in 7-14 days with early diagnosis and treatment.
• Most cases of infection with C pneumoniae are mild and usually respond to treatment in an outpatient setting. Patients with underlying disease or with concurrent infection (eg, pneumococcal bacteremia) can develop severe illness.
• Most patients with C trachomatis infection are moderately ill and respond to appropriate antibiotics. The course is protracted if untreated.

Patient Education

• C psittaci: Educate patients about transmission of the disease. Suspected birds should be isolated until a veterinarian can examine them.
• C pneumoniae: Educate patients about the possible protracted course of illness and about the need for re-treatment if symptoms recur or worsen.
• C trachomatis: Educate the parents of infected children about sexually transmitted diseases and safe sex. Screening of high-risk populations for asymptomatic infections and partner notification and treatment are also important.
• For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center. Also, see eMedicine's patient education article Chlamydia.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• C psittaci
• • Failure to consider the diagnosis in patients with community-acquired pneumonia or with fever of unknown origin who are not responding to treatment
  • Failure to report cases to the appropriate health authorities
  • Failure to investigate the possible source of the infection
  • Failure to ask veterinarians for evaluation and treatment of birds that are suspected sources of human infection
• C pneumoniae - Failure to consider the diagnosis in patients with bronchitis or community-acquired pneumonia and failure to treat with appropriate antibiotics
• C trachomatis - Failure to evaluate mothers of infected infants and their sexual partners and failure to treat appropriately

Special Concerns

• Pregnancy: Avoid tetracyclines.
• Pediatric patients
• • Avoid tetracyclines in children younger than 9 years.
  • In younger children, C trachomatis infection can be acquired through sexual abuse.
• Geriatric patients: If these patients have an underlying disease, infection with C pneumoniae or C psittaci can be fatal.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Andersen P. Pathogenesis of lower respiratory tract infections due to Chlamydia, Mycoplasma, Legionella and viruses. Thorax. Apr 1998;53(4):302-7. [Medline].
• Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention. MMWR Recomm Rep. May 2 1997;46:1-55. [Medline].
• Centers for Disease Control and Prevention. Compendium of measures to control Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis), 2000. Centers for Disease Control and Prevention. MMWR Recomm Rep. Jul 14 2000;49:3-17. [Medline].
• Crosse BA. Psittacosis: a clinical review. J Infect. Nov 1990;21(3):251-9. [Medline].
• Edelman RR, Hann LE, Simon M. Chlamydia trachomatis pneumonia in adults: radiographic appearance. Radiology. Aug 1984;152(2):279-82. [Medline].
• Grayston JT. Infections caused by Chlamydia pneumoniae strain TWAR. Clin Infect Dis. Nov 1992;15(5):757-61. [Medline].
• Ieven MM, Hoymans VY. Involvement of Chlamydia pneumoniae in atherosclerosis: more evidence for lack of evidence. J Clin Microbiol. Jan 2005;43(1):19-24. [Medline].
• Johnston WB, Eidson M, Smith KA, Stobierski MG. Compendium of chlamydiosis (psittacosis) control, 1999. Psittacosis Compendium Committee, National Association of State Public Health Veterinarians. J Am Vet Med Assoc. Mar 1 1999;214(5):640-6. [Medline].
• Kauppinen M, Saikku P. Pneumonia due to Chlamydia pneumoniae: prevalence, clinical features, diagnosis, and treatment. Clin Infect Dis. Dec 1995;21 Suppl 3:S244-52. [Medline].
• Littman AJ, Jackson LA, White E, Thornquist MD, Gaydos CA, Vaughan TL. Interlaboratory reliability of microimmunofluorescence test for measurement of Chlamydia pneumoniae-specific immunoglobulin A and G antibody titers. Clin Diagn Lab Immunol. May 2004;11(3):615-7. [Medline].
• Massachusetts General Hospital. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1998. Pneumonia and the acute respiratory distress syndrome in a 24-year-old man. N Engl J Med. May 21 1998;338(21):1527-35. [Medline].
• Schneeberger PM, Dorigo-Zetsma JW, van der Zee A, van Bon M, van Opstal JL. Diagnosis of atypical pathogens in patients hospitalized with community-acquired respiratory infection. Scand J Infect Dis. 2004;36(4):269-73. [Medline].
• Telfer BL, Moberley SA, Hort KP, Branley JM, Dwyer DE, Muscatello DJ, et al. Probable psittacosis outbreak linked to wild birds. Emerg Infect Dis. Mar 2005;11(3):391-7. [Medline].
• Thom DH, Grayston JT. Infections with Chlamydia pneumoniae strain TWAR. Clin Chest Med. Jun 1991;12(2):245-56. [Medline].
• Tipple MA, Beem MO, Saxon EM. Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than 6 months of age. Pediatrics. Feb 1979;63(2):192-7. [Medline].

Article Last Updated: Feb 13, 2007