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.

2. accurately describe how to perform a mantoux test and interpret the results.

3. describe any peculiar signs or symptoms and identify etiological agent that causes them. Know the fungal forms of the dimorphic fungi that can be found in the lung.

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: 

     A. Typical Pneumonia Syndrome
     B. Atypical Pneumonia Syndrome
     C. Chronic Pneumonias
     D. Pneumonias of the Newborn Period and Infancy
     E. Pneumonia in the Aspiration-Prone Patient
     F. Pulmonary Infection in the Immunocompromised Host

C. Chronic Pneumonias:

These pneumonias develop gradually over a period of weeks to months and are caused by numerous microorganisms. Noninfectious as well as infectious processes can result in chronic pneumonia however, we will only be concerned with the infectious causes of chronic pneumonia.

Early diagnosis of chronic pneumonias requires careful attention to certain clinical and epidemiological features (also refer to table below). The most useful epidemiologic characteristics relate to Melioidosis, South American blastomycosis, echinococcosis and paragonimiasis can only be acquired outside of the U.S. and therefore a history that lacks travel to other countries would exclude these agents in our differential diagnosis. Coccidioides (Southwestern U.S.), Histoplasma (major river valleys along Mississippi and Ohio), and Blastomyces (Southeastern U.S.) all have endemic areas within the U.S. Travel to other states on vacation and where a patient resides in the U.S. might also be quite useful. Occupational history, hobbies, and personal habits are helpful. Coccidioidomycosis is associated with people doing any excavation work. Histoplasmosis is often found in bird and bat feces and therefore a problem for spelunkers, barn cleaners, and bridge painters. Sporotrichosis is a occupational hazard for gardeners and vegetable produce handlers. People who eat raw seafood in endemic areas for Paragonimiasis are more likely to acquire this parasitic infection.

Dark-skinned people and pregnant women show an increased tendency to develop disseminated or chronic pulmonary forms of Coccidioides immitis. White-skinned males are more likely to develop chronic cavitary histoplasmosis. Nocardiosis, cryptococcoses and mycobacterial disease are associated with hosts with defects in cell-mediated immunity. Opportunistic fungal infections are also more common in immunocompromised patients (histoplasmosis, blastomycosis, coccidioidomycosis).

1. Clinical, Radiologic, and Laboratory Features

Often times the patient experiences low grade fever, anorexia, significant weight loss, a productive cough, hemoptysis, chest pain and dyspnea (onset very gradual). A putrid odor of the sputum is a sure indication of an anaerobic infection.

Also, certain microorganisms can infect extrapulmonary sites which helps to narrow down the number of possible causative agents.

Disease  Location  Source/ Mode 
of Spread 		 Predisposing Underlying Conditions  Extrapulmonary manifestations  Characteristic Chest X-ray
Actinomycosis Worldwide Normal oral flora/Aspiration None Rib destruction Cutaneous sinuses Mass lesion or dense infiltrate, cavitation, spread to pleura and chest wall
Nocardiosis  Worldwide Soil decaying vegetable 
matter/ Inhalation 		 Defect cell-mediated immunity; 
High dose corticoste- 
roid therapy; Alveolar proteinosis Chronic granulo- matous 
disease of childhood		 Brain abscess Skin and subcutaneous abscess Confluent broncho-
pneumonia; Cavitation Pleural and chest wall involvement 
Melioidosis 
B. pseudomallei		 Between 20° N and 20° S latitudes in S.E. Asia  Soil, stagnant water/Inhalation None  Skin and subcutaneous 
abscess 		 Lymphadenitis, Nodular infiltrates in upper lobes Cavitation
Mixed anaerobic pleuropulmonary disease Worldwide  Normal oral flora/Aspiration  Alcoholism Neurologic disease Esophageal disorder Seizure disorder Recent 
general anesthesia 		 Brain abscess Dependent 
lung segments, single or multiple 
cavities with surrounding infiltrate; frequent air fluid level; frequent 
pleural involvement
Tuberculosis Worldwide  Person-to-person  Alcoholism Silicosis Gastrectomy Defective cell-mediated immunity Diabetes mellitus Corticoste- roid therapy  Meningitis, osteomyelitis Lymphadenitis Infiltration of liver 
and bone marrow Pericarditis Genitourinary involvement 
Addison's disease 		 Multiple thick-walled cavities with surrounding infiltrate in upper lobe, often bilateral 
M. kansasii Worldwide, but especially Texas, Louisiana, Chicago  Unknown  Chronic obstructive pulmonary disease (COPD) Silicosis  Indistinguish- able from tuberculosis; pleural involvement rare 
M. avium-
intracellulare		 S.E. United States  Soil COPD Silicosis Defective cell-mediated immunity  Rare except in immuno- compromised hosts See above
North American blastomycosis 

broad-based budding yeast in tissue

 S.E. and Mid-Atlantic United States; Great Lakes region; Manitoba; Africa  Soil, Domestic animals  None  Skin, bone and genito-urinary tract Fibronodular, interstitial or alveolar infiltrates, often segmental or lobar 
Coccidioidomycosis

Arthroconidia in vitro 

Spherule in tissue

 S.W. United States; parts Central America Soil  Greater tendency to disseminate in dark-skinned people or pregnant females Skin, bone or meninges  Thin-walled, solitary cavities, segmental, alveolar infiltrate with hilar adenopathy
Histoplasmosis

tuberculate macroconidia in vitro

yeast form in tissue

 Ohio and Mississippi valleys; endemic foci in 31 states Soil contaminated with large amount of bird or bat excreta  Extremes of life for disseminated disease; emphysema for chronic cavitary histoplasmosis  Oral mucosal ulcerations, hepato- splenomegaly; infiltration of bone marrow, Addison's disease, mediastinitis Thick-walled, expanding cavities, interstitial or pathy, nodular infiltrates with hilar adenopathy
Disease  Location  Source/ Mode of Spread  Predisposing Underlying Conditions  Extrapulmonary Manifestations  Characteristic Chest X-ray
Crypto- coccosis  Worldwide Soil contam- inated with bird droppings  Defects in 
cell-mediated 
immunity; corticosteroid 
therapy; lympho- proliferative disorders; alcoholism, diabetes mellitus 		 Meninges, skin, occasionally bone  Nodular dense infiltrates in 
lower lobes; cavitation rare 
South 
American blasto- 
mycosis 		 South and Central America Soil  None  Skin, oral 
mucosa, lymph nodes		 Bilateral 
alveolar 
infiltrates in 
lower lobes; 
often interstitial infiltrates 

broad-base budding yeast 
in tissue
Sporo- trichosis  Worldwide  Vegetable matter None  Upper lobe, thin-walled cavities, 
unilateral
Paragon- imiasis  Far East Asia; India; Africa; Central and South America  Consumption of raw or pickled fresh water crustacea  None Rarely abdominal 
or central nervous system 
involvement 		 Cavity often 
with patchy infiltrates, 
pleural effusion 
Echino- coccosis  Greece; Lebanon and other sheep and cattle-raising areas  Ingestion of material contaminated with dog feces None  Hepatic cysts Rounded, 
nodular lesions
Amebiasis  Worldwide, primarily under-developed countries  Fecal-oral contamination Male homosexuals  Intestinal amebiasis Hepatic abscess Infiltrative or cavitary lesion
in right lower 
lobe, often 
with right 
pleural effusion
Laboratory tests will demonstrate only nonspecific abnormalities in most of the cases. Disseminated tuberculosis and histoplasmosis can cause leukopenia or pancytopenia as well as abnormal liver function studies. Eosinophilia associated with chronic pneumonia should suggest one of the parasitic microorganisms.

2. Diagnosis

These are five basic modalities that can aid in diagnosis:

  1. Smears and cultures of sputum.
  2. Smears and cultures from extrapulmonary sites.
  3. Skin testing.
  4. Serologic testing.
  5. Invasive diagnostic methods.
One should begin with an examination of the sputum. A Gram stain, acid fast stain, NaOH wet mount, or 10% KOH wet mount can be helpful depending on the clinical and epidemiological circumstances. Gram stain for stainable bacteria like Burkholderia. An acid fast stain for Mycobacteria. Chest radiographs of Mycobacterial pneumonia can reveal granulomatous lesions called ghon complexes. A modified acid fast stain for Nocardia. KOH wet mounts for fungal infections and a NaOH wet mount for Paragonimus westermanii infections.

Culture of the sputum depends on the sample. Anaerobes like Actinomyces require translaryngeal aspiration and culture in the absence of oxygen. Some of the organisms like Nocardia require 3 to 4 days to grow even though they are aerobes and since sputum cultures are routinely discarded at 48 hours you need to inform the lab that you suspect a nocardiosis. Mycobacterial cultures also require special treatments and placement on special media therefore informing the lab of such infections is essential.

Culture of fungi will vary with the organism. Generally, cryptococcoses is hard to obtain from the lung (only about 50% recovery). Coccidioidomycosis, blastomycosis, and sporotrichosis are usually quite easy to culture (about 70-100% recovery). Culturing of pleural fluid, skin, urine, prostate secretions, may provide material that will yield a positive culture and definitive diagnosis.

Skin testing is of limited value for determining a fungal etiology, however, it is very useful in the diagnosis of tuberculosis. Conversion from a recent negative skin test to a positive test is a strong indication of tuberculosis in adults. The Mantoux test requires 48-72 hours before it is read. The zone of induration is read not the zone of erythema. Click here for proper way to inject and measure the results of the Mantoux test.. Whether a reaction to the Mantoux tuberculin skin test is classified as positive depends on the size of the induration and on the person's risk factors for TB.

An induration of 5 or more millimeters is considered a positive reaction for the following people:

  1. People with HIV infection
  2. Close contacts of people with infectious TB
  3. People with chest x-ray findings suggestive of previous TB disease
  4. People who inject illicit drugs and whose HIV status is unknown
An induration of 10 or more millimeters is considered a positive reaction for the following people:
  1. People born in areas of the world where TB is common (foreign-born persons)
  2. People who inject illicit drugs but who are known to be HIV negative
  3. Low-income groups with poor access to health care
  4. People who live in residential facilities (for example, nursing homes or correctional facilities)
  5. People with medical conditions that appear to increase the risk for TB (not including HIV infection), such as diabetes
  6. Children younger than 4 years old
  7. People in other groups likely to be exposed to TB, as identified by local public health officials
An induration of 15 or more millimeters is considered a positive reaction for people with no risk factors for TB. In most cases, people who have a very small reaction or no reaction probably do not have TB infection. Positive tests in children is highly suggestive of infection. False-positive reactions can be caused by infection with nontuberculous mycobacteria or vaccination with BCG. For more information go to the self study modules available from the CDC; not required for test in ID.

Serology can be very useful in assisting you in diagnosis. There are serologic tests for Nocardia and for melioidosis. Serology is very useful in diagnosis of fungal and parasitic infections. Complement fixation, hemagglutination, and immunodiffusion tests are available to assist in diagnosis of fungal and parasitic chronic pneumonias.

When all else fails invasive methods to obtain samples directly from the lungs can be obtained. These methods include translaryngeal aspiration, open lung biopsy, needle biopsy of the lung, and transbronchial biopsy via fiberoptic bronchoscopy.

3. Treatment

Due to the large diversity of organisms in this group antibiotic treatment should not be instituted until your sure of the cause of the infection.

D. Pneumonias of the Newborn Period and Infancy:

1. Etiology and Epidemiology

The causes of pneumonia occurring in pediatric patients vary according to the age of the patient.

day 0 to 2 weeks

2 weeks to 6 months 6 months to 5 years 5 years and older Children with cystic fibrosis can acquire a fatal necrotizing pneumonia caused by Pseudomonas aeruginosa. Pneumocystis jirovecii can cause pneumonia in debilitated, malnourished, premature infants and in infants with primary immunodeficiency disorders. Children with altered immune defense mechanisms due to immunosuppressive and cytotoxic therapies for malignancy, collagen-vascular disease or organ transplantation may develop pneumonia due to P. carinii, S. aureus, Gram-negative enteric bacilli, Nocardia, Fungi, Cytomegalovirus and herpes simplex viruses. Influenza virus can cause a severe necrotizing bronchiolitis and pneumonia during epidemics. Secondary pneumonia due to S. pneumonia, S. aureus, H. influenza, and S. pyogenes can follow measles, varicella, or influenza virus infections.

Respiratory distress is the most frequent indication for placing the neonate in an intensive care nursery. LRT infections account for the major portion of pulmonary disease during the first 28 days of life and are an important cause of neonatal mortality and morbidity.

Infectious pneumonias in neonates can be placed in three different categories based on time of acquisition and age presentation.

2. Clinical, Radiologic, and Laboratory Features

Many different agents can cause pneumonia in these patients. As a result the clinical, radiologic, and laboratory features are highly variable.

In viral and Chlamydial pneumonic infections the patient experiences apnea, tachypnea, lethargy, and respiratory distress. Little to no sputum is produced. X-rays reveal diffuse, interstitial or patchy infiltrates. Rarely one sees consolidation. In all but Chlamydial pneumonia a fever (103-104° F) is present. The bacterial infections usually are like that presented for people with typical pneumonia syndrome. Please note, clinical, radiologic, and laboratory features in preterm neonates are quite different but will not be covered in this course.

3. Diagnosis

The etiologic agent most likely to cause infection depends on the age of the patient, if the mother acquired a TORCH infection during pregnancy, if the mother's vagina was colonized with a particular organism, the clinical and radiologic features, as well as the presence of infection in other body sites.

4. Prevention
Screen mother's blood for rubella titers. Also screen her blood for syphilis. A good history may indicate if the mother has had genital herpes. If she has then preparations for a C-section at delivery may be necessary. Obtain vaginal/rectal swab samples at 35 to 37 weeks' gestation and culture for Streptococcus agalactiae (leading cause of neonatal sepsis). If positive for Group B strep then treat the mother while still pregnant with antibiotics to eliminate the organism. This will lower Group B strep infections by about 78%.

E. Pneumonia in the Aspiration-Prone Patient

Aspiration is a process in which matter present in the oropharynx is carried through inhalation into the lower tracheobronchial tree. Usually the matter is cleared from the lungs however, if the person is compromised in some fashion or inhales large amounts of matter a pneumonia can result.

Aspiration includes several aspiration syndromes.

1. Epidemiology and Etiology

The following conditions predispose patients to aspiration pneumonia.

Aspiration pneumonia is an endogenous infection. The infection is usually polymicrobial. The microorganisms can vary depending on whether the infection is community-acquired or hospital-acquired.
 
COMMUNITY ACQUIRED HOSPITAL ACQUIRED
Obligate anaerobes
  • Fusobacterium spp.
  • Bacteroides spp.
  • Prevotella spp.
  • Porphyromonas spp.
  • Peptostreptococci spp.
 Obligate anaerobes 
  • Fusobacterium spp.
  • Bacteroides spp.
  • Prevotella spp.
  • Porphyromonas spp.
  • Peptostreptococci spp.
Facultative aerobes 
  • Streptococcus pneumoniae 
Rarely
  • Klebsiella pneumoniae 
  • Staphylococcus aureus 
 Facultative aerobes
  • Staphylococcus aureus
  • Klebsiella pneumoniae
  • Proteus sp.
  • Pseudomonas sp. 
  • Serratia sp.
  • Escherichia coli
Notice the major difference between hospital and community acquired infections is the facultative aerobes.

2. Clinical, Radiographic, and Laboratory Features

Aspiration pneumonia is much like "typical" pneumonia. However, the possibility of necrotizing pneumonia and lung abscess are more likely in aspiration pneumonia. Often times the sputum has a very foul odor that is pathognomonic for anaerobic lung infections.

3. Diagnosis

This syndrome is a lot like "Typical" pneumonia except for recurrent chills, pneumonia in dependent lung segments, and growth of normal flora on routine sputum culture. Some patients (50%) will produce foul smelling sputum. To get a definitive diagnosis translaryngeal aspiration must be performed. However, this is a dangerous procedure and usually the patients are treated empirically on the basis of predicted bacteriology.

F. Pulmonary Infections of the Immunocompromised Patient

These patients are often troubled with respiratory infections which due to their poor immunologic response to invaders are in serious trouble. Unfortunately, many different organisms can cause respiratory disease in these patients. The patients prognosis is often linked to whether they have neutropenia. Patients with neutropenia are often quite rapidly killed by pneumonic infections and require aggressive diagnostic methods (open lung biopsy) and treatments.

Combination antimicrobial therapy is often used to cover the large number of possible organisms causing disease.

1. Epidemiology and Etiology

Most pulmonary infections of the immunocompromised patient are bacterial. The following organisms can cause infections:

Bacteria (most common to least common)

Viruses Protozoa Fungi Fungi seen only in immunocompromised patients:
2. Diagnosis

A very good history and physical exam will help a lot. Knowledge of the most common organism causing pneumonia in a particular circumstance is also important. Acute onset of symptoms usually indicate a bacterial or Aspergillus infection. Subacute onset of symptoms indicate a viral, Pneumocystis, or Nocardial infection. A chronic onset of symptoms suggest infection due to mycobacteria, Nocardia, or fungi. Usually sputum is not produced in sufficient amounts to aid in diagnosis. Blood cultures can be useful and should be obtained. Skin tests are often useless because the person is unable to mount a T cell response. If samples prove useless and the patient is rapidly deteriorating even during empiric antimicrobial treatment then translaryngeal aspirates, open lung biopsy, or percutaneous needle biopsy are necessary to determine the exact etiologic agent.

Note: AIDS patients have a lot of problems with pneumonia and are usually infected with Pneumocystis jiroveciior Mycobacteria.
 

Click on image to get proper orientation of the figure

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.