eMedicine Specialties > Pulmonology > Infectious Lung Diseases
Chlamydial Pneumonias
Updated: Oct 15, 2008
Introduction
Background
Three chlamydial organisms are pathogenic to humans: Chlamydophila (formerly Chlamydia) pneumoniae, Chlamydophila (formerly 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, because almost any bird 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 susceptible host cells. The organism subsequently produces cytoplasmic inclusions in the infected cells. The cells release the matured inclusions to infect adjacent cells.
The mode of transmission is different between 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.[1 ]Birds known to cause ornithosis include cockatiels, parrots, parakeets, macaws, 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 10-20% of community-acquired pneumonia cases among adults.[2 ]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 1988-1998, 813 cases of psittacosis in humans were reported to the US Centers for Disease Control and Prevention (CDC).[3 ]Approximately 70% of the psittacosis cases with a known source of infection resulted from exposure to pet birds. 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/or nasopharyngitis that in some cases develops into neonatal pneumonitis.
Mortality/Morbidity
- C psittaci: 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.
- C pneumoniae: The mortality rate from C pneumoniae infection was 9.8% in one meta-analysis.[4 ]Secondary infection, such as pneumococcal bacteremia, or the presence of severe underlying disease is associated with increased mortality.[5 ]A Canadian study reported a mortality rate of 4.9% with C pneumoniae pneumonia, which is similar to the rate for bacteremic pneumococcal pneumonia (5.4%) and the overall cohort of community-acquired pneumonia (9.4%).[6 ]
- C trachomatis: Most infants with C trachomatis 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.[7 ]Adult cases have been reported in immunocompromised hosts.[8 ]
Clinical
History
- C psittaci
- Exposure to birds, especially sick ones, is a clue to the diagnosis in a patient with pneumonia and splenomegaly. Pet shop employees and poultry industry workers are also 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 of 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 (rhinitis, laryngitis, pharyngitis, sinusitis) in 1-4 weeks.
- Most persons with C pneumoniae infections are asymptomatic, and most have relatively mild respiratory illnesses.
- 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 (fever without elevated pulse), which is also seen in Q fever, typhoid fever, and Legionnaires’ disease[9 ]; somnolence; splenomegaly; and an erythematous, blanching, maculopapular rash (eg, Horder spots) in the presence of pneumonia suggest ornithosis. Rose spots look very similar to Horder spots and are observed in persons with typhoid fever.
- 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 (rare), splinter hemorrhages, superficial venous thromboses, acrocyanosis, and erythema nodosum, may be 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, can cause chlamydial pneumonia.
Differential Diagnoses
| Influenza | Psittacosis |
| Legionnaires Disease | Q Fever |
| Mycoplasma Infections | Tuberculosis |
| Pneumonia, Bacterial | Tularemia |
| Pneumonia, Fungal | |
| Pneumonia, Viral |
Other Problems to Be Considered
C trachomatis infant pneumonia
Respiratory syncytial virus infection
Bordetella pertussis infection
Infection with other respiratory viruses
Workup
Laboratory Studies
- C psittaci
- Single serum titers are insensitive and nonspecific. Confirmation with paired acute and convalescent sera is advised.
- According to CDC case definitions,[3 ]a confirmed case involves (1) isolation of the organism by culture or (2) compatible clinical illness with a 4-fold rise in complement-fixing (CF) or microimmunofluorescence (MIF) antibodies against C psittaci (to a reciprocal titer of 32 or greater by paired sera at least 2 wk apart) or detection of immunoglobulin M (IgM) titer of 16 or greater against C psittaci by MIF . Serologic tests are preferred because culture is difficult and hazardous.
- 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 by MIF or CF after the onset of symptoms. The CDC accepts human specimens for the diagnosis of C psittaci infection (404-639-3563).[10 ]
- A CF test can cross-react with C pneumoniae and C trachomatis. MIF and polymerase chain reaction assays can be used to distinguish C psittaci infection from infection with other chlamydial species.
- A third serum sample may be necessary to confirm the diagnosis because antibiotic treatment can delay or diminish the antibody response. All serologic tests should be performed simultaneously at the same laboratory.
- C pneumoniae
- The commonly used serologic criteria are an IgM titer exceeding 1:16 or a 4-fold increase in the immunoglobulin G (IgG) titer by MIF.[11 ](Note: A CF test cross-reacts with C psittaci.) However, serologic testing is poorly standardized and studies have shown poor reproducibility.[12,13,14 ] In addition, the presence of a single elevated IgG titer may not be reliable because elderly patients can have persistently elevated IgG titers due to 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.
- 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 remains experimental.
- Cell culture with oropharyngeal swabs is probably the best test, but it requires specialized culture techniques. It is performed only 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 levels 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, and 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.[8 ]
Other Tests
- C pneumoniae: The white blood cell count is usually not elevated in C pneumoniae infection. Alkaline phosphate levels may be elevated.
- 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
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
- Clinicians must treat empirically because rapid testing is not readily available and antibiotic therapy is usually completed before the results of serology testing become available.
- Doxycycline is the treatment of choice except in children younger than 9 years and in 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 for C pneumoniae pneumonia by the US Food and Drug Administration. 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 been reported. It is contraindicated in patients with myasthenia gravis.
- Fluoroquinolones, including levofloxacin (500 mg PO/IV qd for 10-14 d or 750 mg PO/IV qd for 5 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 marketed 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/or 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/or 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/or sexually transmitted disease specialists.
Medication
The goals of pharmacotherapy are to eradicate infection, reduce morbidity, and prevent complications.
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.[15 ]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.
Tetracycline (Sumycin)
Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections.
Dosing
Adult
500 mg PO qid
Pediatric
<8 years: Not recommended
>8 years: 20-40 mg/kg/d PO divided q6h
Interactions
Bioavailability of oral dose decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants; concurrent use with methoxyflurane may cause severe renal impairment and, possibly, death
Contraindications
Documented hypersensitivity; severe hepatic dysfunction; renal failure
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Doxycycline (Vibramycin)
Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Treatment of choice for C pneumoniae infection.
Dosing
Adult
100 mg PO/IV bid for 10-14 d
Pediatric
<8 years: Not recommended
>8 years: 4.4 mg/kg/d PO/IV divided bid; not to exceed 200 mg/d on day 1 or 2.2 mg/kg/d PO/IV qd/bid; not to exceed 100 mg/d
Interactions
Bioavailability of oral dose decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; however, absorption not markedly influenced by simultaneous ingestion of food or milk; can increase hypoprothrombinemic effects of anticoagulants; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Contraindications
Documented hypersensitivity; severe hepatic dysfunction; myasthenia gravis
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; esophageal ulcerations
Erythromycin (E.E.S., E-Mycin, Ery-Tabs)
Considered bacteriostatic, but may be bactericidal in high concentrations against low inoculum of bacteria. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half the total daily dose may be taken q12h. For more severe infections, double the dose.
Dosing
Adult
500 mg PO/IV q6h; may be intolerable at higher doses
Pediatric
<4 months: 20-40 mg/kg/d PO divided q6h
>4 months: 30-50 mg/kg/d PO divided q6h or 50 mg/kg/d IV divided q6h; avoid IM use
Interactions
Coadministration may increase toxicity of protease inhibitors, theophylline, digoxin, carbamazepine, methylprednisolone, disopyramide, ergotamine, terfenadine, astemizole, triazolam, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis; monitor phenytoin and hexobarbital levels
Contraindications
Documented hypersensitivity; hepatic impairment; coadministration with terfenadine (recalled from US market) or astemizole (recalled from US market)
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur; transient deafness may occur with high doses
Clarithromycin (Biaxin)
Semisynthetic macrolide antibiotic. Treats mild-to-moderate infections. May be bacteriostatic or bacteriocidal, depending on concentration used.
Dosing
Adult
500 mg PO bid or 1 g PO qd (Biaxin XL) for 7-14 d; dose should be halved or dosing interval doubled in patients with severe renal impairment (CrCl <30 mL/min)
Pediatric
<6 months: Not established
>6 months: 7.5 mg/kg PO bid for 10 d; not to exceed 1000 mg/d
Interactions
Decreased zidovudine levels; may increase sildenafil (Viagra) levels; toxicity increases with coadministration of fluconazole, astemizole (recalled from US market), and pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants (carefully monitor PT during therapy), cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; cardiac arrhythmia may occur with coadministration of cisapride; arrhythmia and increase in QTc intervals occur with disopyramide
Contraindications
Documented hypersensitivity; coadministration of pimozide
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer 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; adverse effects include diarrhea, nausea, abnormal taste, dyspepsia, abdominal discomfort, and headache in adults; diarrhea, vomiting, abdominal pain, rash, and headache are more common pediatric adverse effects
Postmarketing experience and rare adverse effects include Stevens-Johnson syndrome, glossitis, stomatitis, oral moniliasis, reversible hearing loss, alterations in sense of smell, behavioral changes, confusional states, depersonalization, hallucinations, insomnia, nightmares, tinnitus, vertigo, hepatocellular and/or cholestatic hepatitis with or without jaundice, hepatic failure, and ventricular arrhythmia (including ventricular tachycardia and torsades de pointes in individuals with prolonged QTc intervals)
Azithromycin (Zithromax)
Derived from erythromycin. Treats mild-to-moderate microbial infections.
Dosing
Adult
Day 1: 500 mg PO
Days 2-5: 250 mg PO qd
Community-acquired pneumonia: 500 mg PO/IV qd for 7-10 d
Pediatric
<6 months: Not established
Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
<16 years: IV use not established
Interactions
May increase toxicity of theophylline, ergots, warfarin, and digoxin; increases effect and decreases excretion of triazolam; elevated levels of carbamazepine, hexobarbital, and phenytoin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Contraindications
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzyme levels and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients
Adverse effects include diarrhea, nausea, and abdominal pain; rare adverse effects include chest pain, dyspepsia, constipation, anorexia, flatulence, pseudomembranous colitis, gastritis, headache (otitis media dosage), reversible hearing loss, hyperkinesia, dizziness, agitation, nervousness, insomnia, fever, fatigue, malaise, erythema multiforme, pruritus, urticaria, and conjunctivitis
Telithromycin (Ketek)
First antibiotic in a new class called ketolides. Blocks protein synthesis by binding to 50S ribosomal subunit (23S rRNA at domain II and V). Resistance and cross-resistance have not been observed.
Dosing
Adult
800 mg PO qd for 7-10 d
Pediatric
<13 years: Not established
Interactions
Many drug interactions; HMG-CoA reductase inhibitors (eg, simvastatin, atorvastatin, lovastatin) should be avoided because of increased myopathy risk when coadministered; withhold HMG-CoA reductase inhibitors for duration of therapy; CYP3A4 inhibitor and substrate; coadministration with other CYP3A4 inhibitors (eg, itraconazole, ketoconazole) decreases elimination and increases C max and AUC; CYP3A4 inducers (eg, rifampin) decrease C max and AUC by 79% and 86%, respectively; increases C max and AUC of other CYP3A4 substrates (eg, cisapride, pimozide, simvastatin, lovastatin, atorvastatin, midazolam, triazolam); increases digoxin and theophylline serum levels; decreases sotalol C max and AUC secondary to decreased absorption; caution with other drugs that increase QTc interval (eg, quinidine, procainamide, dofetilide)
Contraindications
Documented hypersensitivity; coadministration with cisapride, pimozide, quinidine, procainamide, dofetilide, rifampin, or ergot alkaloids; myasthenia gravis (black box warning); history of hepatitis and/or jaundice with use of macrolides
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in severe renal impairment (data limited); consider diagnosis of pseudomembranous colitis if diarrhea occurs following antibiotic treatment; may prolong QTc interval, caution with heart conduction abnormalities; common adverse effects include diarrhea and nausea (7-10%); may rarely cause visual disturbances or increased liver enzyme levels; acute hepatic failure and severe liver injury (in some cases fatal) have been reported—if clinical hepatitis or liver enzyme level elevations combined with other systemic symptoms occur, permanently discontinue
Levofloxacin (Levaquin)
Second-generation quinolone. Acts by interfering with DNA gyrase in bacterial cells.
Dosing
Adult
500 mg PO/IV qd for 7-14 days or 750 mg PO/IV qd for 5 d
Pediatric
Not recommended
Interactions
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose in renal function impairment; tendon rupture can occur (black box warning), especially in older patients with the concurrent use of steroids; discontinue if a patient experiences pain or tendon rupture
Moxifloxacin (Avelox)
Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.
Dosing
Adult
400 mg PO qd for 7–14 d
Pediatric
Not recommended
Interactions
Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS-stimulating effect; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Contraindications
Documented hypersensitivity; pediatric patients, unless benefits outweigh risks (as in cystic fibrosis)
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; prolonged QT interval on ECG and ventricular arrhythmias may occur
Tendon rupture can occur (black box warning), especially in older patients with the concurrent use of steroids; discontinue if a patient experiences pain or tendon rupture
Follow-up
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 60%.[2 ]
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.[16 ]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 an 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 otitis, erythema nodosum, exacerbations of asthma, endocarditis, Guillain-Barré syndrome, and encephalitis.
- 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.[17 ]
- 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 clinical course may be 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
Medicolegal Pitfalls
- C psittaci
- Failure to consider the diagnosis in patients with community-acquired pneumonia, especially those with bird exposure or fever of unknown origin, who are not responding to treatment
- Failure to report cases to an appropriate health authority
- Failure to investigate the possible source of infection
- Failure to ask a veterinarian 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 an appropriate antibiotic
- C trachomatis - Failure to evaluate mothers of infected infants and their sexual partners and treat them 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: Infection with C pneumoniae or C psittaci can be fatal, especially in elderly patients with an underlying disease.
References
Crosse BA. Psittacosis: a clinical review. J Infect. Nov 1990;21(3):251-9. [Medline].
Ewig S, Torres A. Is Chlamydia pneumoniae an important pathogen in patients with community-acquired pneumonia?. Eur Respir J. May 2003;21(5):741-2. [Medline]. [Full Text].
Centers for Disease Control and Prevention. Compendium of measures to control Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis), 2000. MMWR Recomm Rep. Jul 14 2000;49:3-17. [Medline]. [Full Text].
Fine MJ, Smith MA, Carson CA, Mutha SS, Sankey SS, Weissfeld LA, et al. Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis. JAMA. Jan 10 1996;275(2):134-41. [Medline].
File TM Jr, Tan JS, Plouffe JF. The role of atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in respiratory infection. Infect Dis Clin North Am. Sep 1998;12(3):569-92, vii. [Medline].
Marrie TJ, Peeling RW, Reid T, De Carolis E. Chlamydia species as a cause of community-acquired pneumonia in Canada. Eur Respir J. May 2003;21(5):779-84. [Medline]. [Full Text].
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].
Edelman RR, Hann LE, Simon M. Chlamydia trachomatis pneumonia in adults: radiographic appearance. Radiology. Aug 1984;152(2):279-82. [Medline].
Cunha BA. The atypical pneumonias: clinical diagnosis and importance. Clin Microbiol Infect. May 2006;12 Suppl 3:12-24. [Medline].
Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance. MMWR Recomm Rep. May 2 1997;46:1-55. [Medline].
Dowell SF, Peeling RW, Boman J, Carlone GM, Fields BS, Guarner J, et al. Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada). Clin Infect Dis. Aug 15 2001;33(4):492-503. [Medline]. [Full Text].
Kumar S, Hammerschlag MR. Acute respiratory infection due to Chlamydia pneumoniae: current status of diagnostic methods. Clin Infect Dis. Feb 15 2007;44(4):568-76. [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].
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. March 2007;44:Suppl 2:S27-72. [Medline]. [Full Text].
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].
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].
Andersen P. Pathogenesis of lower respiratory tract infections due to Chlamydia, Mycoplasma, Legionella and viruses. Thorax. Apr 1998;53(4):302-7. [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].
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].
Keywords
chlamydial pneumonia, psittacosis , ornithosis, Chlamydophila pneumoniae, Chlamydia pneumoniae, C pneumoniae, Chlamydophila psittaci, Chlamydia psittaci, C psittaci, Chlamydophila trachomatis, Chlamydia trachomatis, C trachomatis, Chlamydophila pneumoniae pneumonia, Chlamydophila trachomatis pneumonia, Taiwan acute respiratory pneumonia, TWAR pneumonia, parrot fever, avian chlamydiosis
Contributor Information and Disclosures
Author
Yuji Oba, MD, FCCP, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care, and Environmental Medicine, University of Missouri Health Care
Yuji Oba, MD, FCCP is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Nothing to disclose.
Coauthor(s)
Vamsi P Guntur, MD, MSc, Assistant Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Environmental Medicine, University of Missouri
Vamsi P Guntur, MD, MSc is a member of the following medical societies: American Association for Cancer Research, American College of Chest Physicians, American College of Physicians, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.
Medical Editor
Helen M Hollingsworth, MD, Director, Adult Asthma and Allergy Services, Associate Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, Boston Medical Center
Helen M Hollingsworth, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American Thoracic Society, and Massachusetts Medical Society
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Om Prakash Sharma, MD, FRCP, FCCP, DTM&H, Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine
Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine
Disclosure: Keck School of Medicine, USC None None
CME Editor
Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
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Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
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