Atypical bacterial pneumonia

I. What every physician needs to know.

Atypical pneumonia is a term first introduced in the 1930s to denote a community-acquired pneumonia (CAP) that is clinically different from the illness attributable to Streptococcus pneumoniae.

The three organisms most often associated with atypical pneumonia are Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp, with M. pneumoniae thought to be the most common of the three.

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Historically, it was thought that a distinction was able to be made clinically between pneumonia caused by typical and atypical pathogens. The atypical pneumonias were thought to present with a more insidious and gradual onset. Cough was described as non-productive or, if sputum is present, it was more watery than in typical cases. Prominent extra pulmonary symptoms were more likely to be present with atypical bacteria, including headache, myalgias, fatigue, sore throat, rhinorrhea, nausea, vomiting, and diarrhea. More recent studies, however, suggest that these distinguishing criteria are not reliable.

Current CAP guidelines therefore recommend empiric coverage for both typical streptococcal and atypical microorganisms.

II. Diagnostic Confirmation: Are you sure your patient has atypical bacterial pneumonia?

A. History Part I: Pattern Recognition:

Historically atypical pneumonia was distinguished from classical pneumonia by clinical findings, compared below in Table I. The prominent findings of increased extra pulmonary symptoms and the lesser severity of pulmonary symptoms have been the overarching clinically differentiating features.

Table I.
Atypical Typical (streptococcal)
Gradual onset Sudden onset
Dry cough Productive cough (purulent, rusty or mucoid sputum)
Dyspnea Dyspnea
Fever Fever
  Pleuritic chest pain, splinting
General malaise General malaise
Pulse/temperature dissociation  
Longer duration of illness Shorter duration of illness

However, while the above clinical characteristics have been useful historically, numerous studies have concluded that the clinical signs of infection due to atypical and typical organisms are indistinguishable, and the above may only be relevant to infections caused by M. pneumoniae or C. pneumoniae.

Legionella infection has clinical features that are more like those of typical bacterial pneumonia (Streptococcus, Klebsiella, and Haemophilus). Infection with Legionella should be considered in patients admitted with CAP who have fevers greater than 104ºF, male patients, those with multilobar infiltrates on chest x-ray, and those with gastrointestinal (watery diarrhea) and neurologic complaints (confusion).

B. History Part 2: Prevalence:

Worldwide, an estimated 20-30% of cases of CAP are thought to be due to atypical organisms, although exact numbers are unknown because of the lack of reliable testing for most of the atypical organisms. In the inpatient setting, for patients not admitted to the intensive care unit (ICU), atypical microorganisms may cause as many as 10-15% of pneumonias.

Legionella spp. may represent 10% of CAP in patients admitted to the ICU. C. pneumoniae and M. pneumoniae infections may be complicated by asthma or chronic obstructive pulmonary disease (COPD). C. pneumoniae primarily affects young adults and is most often treated in outpatient settings, but may be a significant contributor to severe CAP in those older than 65.

Atypical organisms may present as severe CAP in patients with compromised respiratory status, such as human immunodeficiency virus (HIV), cystic fibrosis, acute chest syndrome in sickle cell disease, neutropenia, or leukemia).

C. History Part 3: Competing diagnoses that can mimic atypical bacterial pneumonia.

See Table II for organisms to be considered in the differential diagnosis for atypical pneumonia.

Table II.
Etiology  Frequency – not admitted to ICU Frequency – admitted to ICU
Streptococcus pneumoniae   25 17
Legionella pneumophila 3 10
Mycoplasma pneumoniae  6 NA
Chlamydophila pneumoniae 3 NA

ICU: intensive care unit

NA: not applicable

D. Physical Examination Findings.

In addition to the findings of cough and extrapulmonary symptoms mentioned above, the following are signs that may be found associated with these infections. See Table III.

Table III.
Differential diagnosis   Distinguishing features associated with atypical pneumonia
Streptococcus pneumoniae  Presence of prominent extrapulmonary findings
Chlamydia psittaci – psittacosis  Absence of exposure to birds
Francisella tularensis – tularemia Absence of zoonotic exposure (lagomorphs, deer)
Coxiella burnetii – query fever  Absence of zoonotic exposure (infected parturient livestock)
Mycobacterium tuberculosis – tuberculosis  Absence of risk factors, negative PPD
Histoplasma/Blastomyces – fungal infections  Absence of geographical exposure
Influenza/adenovirus – viral infections    Negative on rapid viral testing

PPD: purified protein derivative

Table IV.
Clinical Signs  Mycoplasma pneumoniae  Chlamydophila pneumoniae   Legionella pneumophila
Shock hypotension  –   –   +
Rash      Erythema multiforme  –   –
Neurologic findings/confusion    –  –   +
Bullous myringitis   + (75%)  –  – 
Non-exudative pharyngitis  +  +   – 
Laryngitis  –   +    –
Hemoptysis      –   –   +
Signs of lobar consolidation    –   –   +
Cardiac disease  Myocarditis/pericarditis, heartblock  –   – 
Splenomegaly    –   –    –
Pulse-temperature dissociation  –   –   +
Table V.
  Mycoplasma pneumoniae  Mycoplasma pneumoniae  Chlamydophila pneumoniae    Chlamydophila pneumoniae     Legionella pneumophila       Legionella pneumophila 
Test Procedure  Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity
Culture   >90  50-90  50-70  ?  80   100
Cold agglutinins  (>1:64)     ?  low  NA  NA  NA  NA
Urinary antigen   NA  NA  NA  NA  70-80  100
Complement fixation     75-80  80-90  0 (higly x-  reactive)   0 (higly x-  reactive)   NA  NA
ELISA   90  93  NA  NA  40-75  90-95

ELISA: enzyme-linked immunosorbent assay

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Currently the only readily-available and clinically-useful diagnostic tool available to confirm the presence of one of the atypical organisms is the Urinary Antigen Test (UAT) for L. pneumophila serogroup 1, which accounts for 70-80% of pneumonias caused by Legionella spp. This UAT need not be ordered in all patients though, and is only recommended for patients presenting with presumed severe CAP.

Polymerase chain reaction (PCR) screening of sputum or nasopharyngeal samples promises to afford more rapid and sensitive screening for atypical microorganisms, but these have not yet been routinely adopted or approved by the United States Food and Drug Administration (FDA).

Routine laboratory testing for complete blood count and comprehensive metabolic testing is rarely diagnostic for atypical organisms. However some abnormalities are more likely to be associated with infection by one organism than another and when present, in association with other findings, may support the presence of a specific pathogen. These tend to be more useful in establishing the presence of Legionella spp. and are summarized below:

Legionella infection

  • Elevated serum lactate dehydrogenase (LDH) (more than 700 U/L)

  • Hyponatremia (sodium [Na] less than 130)

  • Hypophosphatemia

  • Minor increase in aspartate transaminase/alanine transaminase (AST/ALT) (less than 2x normal)

  • Leukocytosis is common

  • Microscopic hematuria may be present

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Chest x-ray (CXR) should be obtained on all patients with suspected pneumonia. Historically it was felt that the CXR associated with atypical pneumonia differed significantly from that associated with typical streptococcal pneumonia. The CXR with atypical pneumonia was described as “streaky” or “patchy” as compared to streptococcal pneumonia, which usually presented with focal or lobar consolidations. In the presence of associated laboratory and physical findings the CXR may be supportive of the presence of a specific atypical microorganism. For example, in the case of Legionella spp. infection, the CXR may demonstrate rapidly progressive asymmetrical infiltrates with worsening pleural effusions. In general, however, the CXR is largely non-specific.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

There is no role for routine serologic testing for these atypical organisms. Blood cultures are not recommended for most patients hospitalized with CAP.

As noted above, Legionella spp. UAT, along with S. pneumoniae UAT, is not indicated in all patients presenting with CAP, rather only those with severe symptoms.

Computed tomography (CT) of the chest is rarely indicated in CAP patients. If done, patients with Legionella spp. will have ground glass opacities in the affected lobes. This is very different from the appearance of infection by Chlamydophila or Mycoplasma.

III. Default Management.

  • Thorough history to identify symptoms consistent with atypical pneumonia and immunocompromised status to establish risk for serious illness and for possible exposures to specific pathogens (e.g., travel, zoonotic exposures).

  • Physical examination consistent with pneumonia. Utilize risk stratification tools such as the PORT score (Pneumonia Outcomes Research Trial) and CURB-65 (confusion, urea, respiratory rate, systolic blood pressure) to guide admission and in-hospital placement decisions.

  • Pulse oximetry screening.

  • Chest radiography. Pleural effusion greater than 5cm on a lateral film should have thoracentesis for diagnostic studies and therapeutic value.

  • Laboratory testing directed at a specific pathogen should only be performed when a specific pathogen is suspected based on epidemiologic or clinical suspicion.

  • Obtain sputum cultures prior to initiation of antibiotic therapy.

  • For patients admitted to the ICU, blood cultures, sputum cultures and urine antigen testing (for Legionella spp. and S. pneumoniae) is recommended. Obtain cultures prior to initiating antibiotic therapy.

  • Initiate antibiotic therapy in the emergency department or as soon as possible thereafter. Treatment for atypical bacterial pneumonia is included in CAP guidelines, which recommend either 1) a ß-lactam antibiotic PLUS a macrolide antibiotic (doxycycline may replace the macrolide) or 2) a respiratory fluoroquinolone (especially in patients with penicillin allergies). Macrolide antibiotics are generally effective against all three of the atypical bacterial pneumonia organisms.

A. Immediate management.

Establish the severity of pneumonia and the need for assisted ventilation.

B. Physical Examination Tips to Guide Management.

Patients admitted to the general medical wards who do not show significant improvement within 48-72 hours and have a worsening pulmonary examination should have a repeat CXR. Progressive disease may be indicative of Legionella spp infection.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

There are no specific laboratory tests indicated to monitor response to antibiotic therapy.

D. Long-term management.

There is no specific long-term management associated with the post-hospital course. A follow-up CXR is not indicated given clinical improvement.

E. Common Pitfalls and Side-Effects of Management

Local resistance patterns to antibiotics for common organisms should be known and used to guide therapy. A patient who is not responding to antibiotic therapy should be reassessed for other uncommon causes of CAP. There is no role for the use of adjunctive steroid therapy.

IV. Management with Co-Morbidities

A. Renal Insufficiency.

No change in standard management.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in standard management.

E. Diabetes or other Endocrine issues

No change in standard management.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management.

I. Gastrointestinal or Nutrition Issues

No change in standard management.

J. Hematologic or Coagulation Issues

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

Consider transfer to ICU if the patient clinically worsens.

B. Anticipated Length of Stay.

Most patients should show clinical improvement within 48-72 hours. Anticipated length of stay of non-ICU patients is 3-5 days.

C. When is the Patient Ready for Discharge.

Patients may be discharged with oral antibiotic therapy when:

  • They are afebrile for greater than 24 hours.

  • They are not hypoxemic on ambient air or are stable on a home regimen of supplemental oxygen.

  • They are able to tolerate oral medications.

  • Blood cultures have been negative for 24-48 hours, if obtained.

D. Arranging for Clinic Follow-up

1. When should clinic follow up be arranged and with whom.

Follow-up within 7 days of discharge is usually recommended to ensure progressive improvement of the clinical examination.

2. What tests should be conducted prior to discharge to enable best clinic first visit.


3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.


E. Placement Considerations.

None indicated. In the rare instance where the patient may be required to complete a recommended course of intravenous antibiotics and a peripherally inserted central catheter (PICC) line is placed, appropriate referral to home health care and case management to facilitate antibiotic administration should be made.

F. Prognosis and Patient Counseling.

None specific to CAP.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

First dose of antibiotic administered in the emergency department.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

None specific.

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