Lower Respiratory Tract Infections
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General Goal: To know the major cause of these clinical syndromes and how they are transmitted.

Specific Educational Objectives: The student should be able to:

1. describe the differences between the various syndromes. Know the most common causes of the various clinical syndromes and what persons are more likely to get these infections.

2. describe any peculiar signs or symptoms and identify etiological agent that causes them (bulging fissure, currant jelly sputum, pneumatoceles). 

Reading: Mosby's Color Atlas and Text of Infectious Diseases by Christopher P. Conlon and David R. Snydman. pp. 67-76.

Lecture: Dr. Neal R. Chamberlain

References: 

Since a large number of organisms can produce pneumonia, a physician can often arrive at a more rapid microbiological diagnosis if the pathogens are grouped as causes of one of several, relatively distinct syndromes.

The following syndromes we will discuss are as follows:

A. Typical Pneumonia Syndrome:

The signs and symptoms of this particular syndrome are also seen in other syndromes (some infections of the immunocompromised host, and in the aspiration-prone patient, pneumonias of the newborn and infant). This is because the other syndromes also include bacteria that elicit respiratory symptoms, sudden onset, and purulent sputum. However, the circumstances and immune status of the patient tend to increase the chances of acquiring a different set of bacterial pathogens.

1. Etiology and epidemiology

Community Acquired
Typical pneumonia is usually acquired by bronchogenic spread of the pathogen. The organism may also manifest itself as a suprainfection in patients previously infected by an upper or lower respiratory viral infection. There is no age-specific predisposition, however the incidence of infection increases with advancing age. Most patients are adults above the fifth decade and who have some underlying chronic obstructive pulmonary disease (COPD), cardiovascular or other chronic disease.

Streptococcus pneumoniae is a bacterial pathogen that affects children and adults worldwide. It is a leading cause of illness in young children and causes illness and death among the elderly and persons who have certain underlying medical conditions. Pneumococcal infection causes an estimated 40,000 deaths annually in the United States. Approximately half of these deaths potentially could be prevented through the use of vaccine. Despite appropriate antimicrobial therapy and intensive medical care, the overall case-fatality rate for pneumococcal bacteremia is 15%-20% among adults. The organism colonizes the upper respiratory tract and can cause the following types of illnesses: a) disseminated invasive infections, including bacteremia and meningitis; b) pneumonia and other lower respiratory tract infections; and c) upper respiratory tract infections, including otitis media and sinusitis. Each year in the United States, pneumococcal disease accounts for an estimated 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7 million cases of otitis media.

In adults, 60%-87% of pneumococcal bacteremia is associated with pneumonia. Severe pneumococcal infections result from dissemination of bacteria to the bloodstream and the central nervous system. In the United States, the risk for acquiring bacteremia is lower among white persons than among persons in other racial/ethnic groups (i.e., blacks, Alaskan Natives, and American Indians). Black adults have a threefold to fivefold higher overall incidence of bacteremia (49-58 cases per 100,000 population) than whites (5-8). Rates of invasive pneumococcal disease are exceptionally high among Alaskan Natives and American Indians. At least 500,000 cases of pneumococcal pneumonia are estimated to occur annually in the United States; S. pneumoniae accounts for approximately 25%-35% of cases of community-acquired bacterial pneumonia in persons who require hospitalization. Concomitant bacteremia occurs in approximately 10%-25% of adult patients who have pneumococcal pneumonia

H. influenzae and K. pneumoniae are more commonly seen in patients with COPD, alcoholics, and the elderly.

S. aureus infections are most common in IV drug users, the elderly, in people with a recent influenza virus infection, and in individuals with cystic fibrosis.

P. aeruginosa is also often seen as a cause of pneumonia in patients with cystic fibrosis and those with severely compromised respiratory defenses. Patients on respirators are more likely to develop pneumonia due to P. aeruginosa.

S. pyogenes pneumonia is less common today due to the use of antibiotics to treat upper respiratory tract infections.

N. meningitidis is occasionally seen in epidemics in military recruits. Y. pestis infections are due to environmental exposure to an infected rat population. B. pseudomallei infections are due to exposure with contaminated soil in Southeast Asia.

2. Clinical, Radiologic, and Laboratory Features

If necrosis of the lung occurs, cavities in the lung develop resulting in cavernous or amphoric breathing directly over the cavitary lesion. Pneumonias in the lower lobe regions may cause pain referral to the abdominal region due to diaphragmatic inflammation. Classic radiologic features in advance cases reveal a dense lobar consolidation. The consolidations may involve one or more lobes and be either unilateral or bilateral. A pleural effusion may be present. The most useful laboratory maneuver for the initial diagnosis of typical pneumonia is a gram stain examination of the sputum. Usually the patient will produce copious amounts of purulent or mucopurulent sputum.

Exceptions: patients who are severely dehydrated, patients with obstructive lesions, and patients too weak to mount an effective cough. The odor of the sputum should be noted since anaerobic bacterial infections often times produces a foul smelling sputum.

Microscopic examination of the sputum should reveal numerous PMNs, occasional alveolar macrophages, and many bacteria. Large numbers of squamous epithelial cells suggests contamination with saliva and as a result cannot be used for diagnostic evaluation.

Other samples that should be taken include a blood sample used to culture for bacteria and culture of pleural effusions if present. White blood counts of the blood sample reveal a leukocytosis with a predominance of early forms of PMNs (bands).

3. Diagnosis

Bacterial Pathogens  Susceptibility  Clinical Features  Associated Sites of Infection  Sputum Gram Stain 
S pneumoniae  Children< 2, adults over 65, Splenectomy, Chronic lymphatic leukemia, Multiple myeloma, Sickle cell anemia, Postinfluenza, COPD, smokers  Rusty sputum Single shaking chill  Bacteremia 25-50% Pleural effusions Arthritis Meningitis Endocarditis Sinusitis  Encapsulated lancet-shaped Gram-positive diplococci or short chains Quellung reaction positive
H. influenzae Young children < 2, COPD, Alcohol abusers, Postinfluenza  Pleural effusion common Bacteremia  Otitis Sinusitis Meningitis Epiglottis Facial infection  Small Gram-negative pleomorphic encapsulated bacillus (Group B) Occasionally disease caused by nontypable strains
S. aureus Metastatic infection in parenteral drug abusers or patients with infected intravenous catheters, Postinfluenza, Cystic fibrosis, In hospital aspiration Pleuritic chest pain Multiple thin walled abscesses ("pneumatoceles") Cardiac murmurs  Endocarditis Cerebritis Metastatic abscesses Skin furuncles  Gram-positive cocci in clusters 
S. pyogenes Postinfluenza, COPD Pleural effusion or empyema (up to 90%) Bacteremia 12%  Tonsillitis Mediastinitis Gram-positive cocci in chains Quellung reaction negative
K pneumoniae Alcohol abusers, COPD, Neonates Nosocomial  "Currant jelly" sputum Bulging fissure Lung necrosis  Large Gram-negative rod with capsule
P. aeruginosa Neutropenic, Intubated respiratory therapy, ICU-Burn unit, Cystic fibrosis Green sputum Fulminant course Necrotizing with multiple small and large abscesses Skin lesions (ecthyma gangrenosum) Gram-negative rod (encapsulated in patients with cystic fibrosis) Enteric bacilli Same as P. aeruginosa Variable -- Gram-negative rod
Enteric bacilli  Same as P. aeruginosa Variable -- Gram-negative rod

B. Atypical Pneumonia Syndrome:
These infections can involve Mycoplasma, Chlamydia, Rickettsia, other bacteria, viruses, or fungi. Determining the causative agent requires knowing what the common causes of atypical pneumonia are, as well as knowing the epidemiology, clinical picture, radiologic findings, and laboratory findings. This will provide the presumptive diagnosis. The definitive diagnosis usually requires retrospective serologic tests.

The most common pathogen of this group is Mycoplasma pneumoniae. It ranks second only to S. pneumoniae among all pneumonias due to infectious diseases. The other relatively common cases of atypical pneumonia are Chlamydia pneumoniae, the Influenza viruses and Legionella sp.. M. pneumoniae is now known to be the cause of pneumonia in 20% to 25% of all age groups and to persist in certain persons for weeks to months, resulting in prolonged reduced pulmonary clearance and airway hyperresponsiveness. C. pneumoniae causes approximately 10% of community-acquired pneumonia. The other agents are uncommon in adults or are due to exposure of the host to an unusual source of infection.

Comparative Epidemiologic Features of the Atypical Pneumonias:
Atypical pneumonias Incubation period (days)  Seasonality  Patient Age Exposure to Infected Animal or Sources  Person to person Transmissions  Underlying Chronic Diseases 
Mycoplasma pneumonia  14-21 Year round Adolescents and young adults - +  -
Legionnaire's disease  2-10 Year round (summer peak) Adult Cooling towers, condensers, excavation sites -  + 
Psittacosis  7-14  Year round Adult Psittacine birds, pigeons, turkeys, pet shops, zoos -  - 
Q fever  14-28 Year round Adult  Cattle, sheep, goats, contaminated milk, birthing various livestock -  - 
Tularemia 1-14 Year round  Adult  Rabbits, ticks  -  - 
Anthrax  1-5 Year round Adult  Goat hair/skin, wool, bonemeal fertilizer -  - 
Viral pneumonia  1-3 Winter  All +  +
Histoplasmosis  3-21 Year round All  Chickens, bats, river valleys - -
Coccidioidomycosis  7-28 Year round All  California, Southwest USA - -
2. Clinical, Radiologic, and Laboratory Features

Symptoms of atypical pneumonia include fever, nonproductive cough, and prominent constitutional signs (severe headache, malaise, myalgias) onset is usually more insidious. Physical examinations at most disclose rales and rhonchi. Signs of pulmonary consolidation are rarely present. The radiographic findings usually appear as interstitial patchy bronchopneumonic infiltrates.

There is a lot of overlap in the manifestations of atypical pneumonia however the following table indicates some distinctive features that can aid in differentiation.
Atypical Pneumonias  Clinical Features  Radiographic Features Laboratory Features
Mycoplasma pneumonia Upper respiratory tract symptoms, Bullous myringitis, Hemolytic anemia, Myocarditis, Meningoencephalitis  Occasional pleural effusion  Cold hemagglutinins
Legionnaire's disease  Relative bradycardia, Abdominal pain, Vomiting and diarrhea, Hematuria, Mental confusion  Occasional pleural effusion Abnormal liver and renal function tests Increased CPK
Psittacosis  Relative bradycardia Epistaxis Horder's spots Splenomegaly -- Normal or low leukocyte count
Q fever  Relative bradycardia, Tender hepatomegaly, Endocarditis -- Abnormal liver function tests
Tularemia  Substernal chest pain, Relative bradycardiaBilateral hilar adenopathy common Bilateral hilar adenopathy common, Occasional bloody pleural effusion Normal or low leukocyte count
Anthrax Precordial discomfort, Hemorrhagic meningitis  Mediastinal adenopathy common, Occasional pleural effusion --
Viral pneumonia Upper respiratory tract symptoms -- --
Histoplasmosis  Erythema nodosum, Substernal discomfort  Bilateral hilar adenopathy common tuberculate macroconidia in vitro) 

yeast form in tissue
Coccidioidomycosis Chest pain, Erythema nodosum Bilateral hilar adenopathy common, Occasional pleural effusion Arthroconidia in vitro 

Spherule in tissue
3. Diagnosis

Direct isolation of the organism is not usually performed due to the hazardous nature of some organisms (F. tularensis) and due to the specialized culture techniques needed to allow growth of the organism. Microscopic examination of the sputum is not performed unless a Legionella sp. infection is suspected. This organism is stained with Dieterle silver stain and direct fluorescent antibody staining. A test for Legionella antigen in the urine is available and can be useful. Legionella can now be routinely cultured and this may also aid the physician in determining a definitive diagnosis. An indirect Fluorescent Antibody test to detect antibodies to Mycoplasma pneumoniae is very useful.

Serologies for the various causes of atypical pneumonia include:

  1. Mycoplasma pneumoniae= complement fixation test, IgM by latex agglutination or ELISA, cold agglutinins
  2. Legionella pneumophila= rapid microagglutination test, test for Legionella antigen in the urine.
  3. Chlamydia spp.= microimmunofluorescence, ELISA
  4. Coxiella burnetii= complement fixation test.
Skin testing for histoplasmosis and coccidioidomycosis is performed only if a previous skin test was negative. Frequently, a definitive diagnosis of an atypical pneumonia is made retrospectively, through employment of serologic tests. A four fold or greater rise in titer between the acute and convalescent sera is confirmatory of an acute infection. However, this is too little too late for treating the patient. A combination of the clinical, epidemiologic, radiographic, and laboratory features can specify a certain etiology so that empiric treatment can begin.

Send comments and email to Dr. Neal R. Chamberlain,  nchamberlain@kcom.edu
Revised 8/2/02
©2002 Neal R. Chamberlain, Ph.D., All rights reserved.