LOWER RESPIRATORY TRACT INFECTIONS.

OVERVIEW

Lower respiratory tract infections cause disease in the alveolar sacs, and the resulting infections are called pneumonia. This section of the handout will discuss the various types of pneumonia (i.e., typical, interstitial, chronic, and fungal pneumonia) and the agents that cause them.

PNEUMONIA

Pneumonia is an infection of the alveoli or the walls of the alveolar sacs. Diagnosis of pneumonia is relatively straightforward; however, since so many microorganisms can cause pneumonia, determining the cause of a patient’s pneumonia can be very difficult.

Etiology

Many microorganisms can cause pneumonia, but most cases are caused by bacteria. The most likely causes of pneumonia depend on various clinical and epidemiological factors. These factors include how the patient acquired the pneumonia (e.g., inhalation, aspiration), where the patient acquired the pneumonia [e.g., community-acquired pneumonia (CAP), health care-associated pneumonia (HCAP)], the age of the patient, the type of pneumonia the patient manifests (e.g., typical versus atypical (interstitial) pneumonia) and the immune status of the patient (i.e., immunocompromised versus immunocompetent). The clinical and epidemiologic factors mentioned above are used to determine the most likely causes of each individual case of pneumonia and have a significant affect on the antimicrobial agents used to empirically treat patients with pneumonia.

The emergence of multi-drug resistant (MDR) bacteria (e.g., methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter, and MDR Enterobacteriaceae) has made the treatment of pneumonia more challenging. MDR bacterial pneumonias are more likely to occur in a health care setting (e.g., hospital, ICU, nursing home). This increase in MDR bacterial pneumonias has resulted in a revised classification of pneumonia. Currently, there are two categories of pneumonia; community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). HCAP contains two subcategories; hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). The etiological agents and the chances of them being a MDR differ depending on the category of pneumonia and the risk factors a patient has. This also has a significant affect on the antimicrobial agents used to treat these patients.

* Standard bacteria refer to the bacteria that commonly cause community-acquired pneumonias. † Respiratory    viruses include influenza A and B viruses, parainfluenza viruses, adenoviruses, and respiratory syncytial virus.

Manifestations

Many patients who are diagnosed with pneumonia mention having previous flu-like symptoms or an upper respiratory tract infection. A patient with pneumonia will frequently continue to have symptoms of upper respiratory tract infection and develop respiratory symptoms that are indicative of a lower respiratory tract infection—cough, dyspnea, sputum production, and tachycardia. Pneumonia is even more likely to be the diagnosis if the patient also has a fever and auscultatory findings that may include abnormal breath sounds, dullness to percussion, wheezes, and crackles (rales). One exception regarding fever is a neonate who diagnosed with afebrile Chlamydia trachomatis pneumonia.

Pneumonias can be classified based on how rapid the pneumonia manifests. Acute onset pneumonias develop within 24–48 hours and are common in patients with typical pneumonia. The patient’s only complaint may be an upper respiratory infection but  manifestations of typical pneumonia rapidly develop—high fever, shaking chills, dyspnea, tachycardia, productive cough with purulent sputum production, toxic facies, and consolidations in the lungs as seen on chest radiographs (Table LRI-8).

Interstitial (Atypical)  pneumonia (interstitial pneumonia) has a subacute onset; it may take several days to 1 week before the patient develops signs and symptoms of pneumonia—low-grade fever, chills, paroxysmal cough with mucoid sputum or no sputum production, well-appearing facies, and infiltrates in the lungs as seen on chest radiographs (Table LRI-8).

Chronic pneumonias can take several weeks to 1 month for symptoms to fully develop. Patients usually present with a history of night sweats, low-grade fever, significant weight loss, productive cough with purulent sputum production, and dyspnea; coin lesions (Ghon focus) in the lungs may be seen on chest radiographs if the patient has M. tuberculosis pneumonia.

Symptoms of aspiration pneumonia are similar to other acute onset pneumonias, except patients experience recurrent chills rather than a shaking chill, and consolidations in the dependent lung segments are seen on chest radiographs. About one half of patients with aspiration pneumonia will produce foul-smelling sputum.

Symptoms of HCAP are like those mentioned above; fever, leukocytosis, increase in respiratory secretions, pulmonary consolidations on physical examination, along with a new or changing radiographic infiltrate or consolidation. Other signs and symptoms may include tachycardia, tachypnea, worsening oxygenation, and increased minute ventilation (Tidal volume x Respiratory rate = minute ventilation; normal 5-8 L/minute).

Radiograph interpretation in a patient with VAP may be difficult in that they may have abnormal chest radiographs even before the pneumonia begins.

Some causes of pneumonia that result in unique signs and symptoms

Epidemiology

Pathogenesis

The microbiota of the lower respiratory tract rarely, if ever, cause pneumonia. Usually, a patient with pneumonia has inhaled or aspirated a pathogenic organism or a new bacterial strain of an organism already dwelling in the lungs. The two most common means of acquiring a lower respiratory tract infection is by inhalation and aspiration. Pathogenic organisms and different strains of bacteria in the microbiota of the lung that enter the alveoli are eliminated by alveolar macrophages. Alveolar macrophages are the most important means of eliminating organisms that get in the alveoli after escaping the defense mechanisms in the upper respiratory tract and the respiratory airways. PMN’s are important in elimination of organisms after an infection and pneumonia has begun.

Once a microorganism enters the alveoli, it can be opsonized by IgG in the fluid lining the alveoli and then be ingested by the macrophage via their Fc receptors.

Many bacteria that cause pneumonia can initially survive in the alveoli due to the following defense mechanisms.

If the organisms survive in the alveoli, microbial growth can cause tissue injury, which stimulates the host to mount an inflammatory response. Tissue injury can occur due to exotoxins produced by a bacterium, cell lysis caused by a virus, or death of alveolar macrophages and dumping of their lysosomal contents in the alveoli due to growth of an organism in the phagocyte. Vascular permeability increases, and PMNs arrive at the area with many of the serum components, attempting to contain and eliminate the organisms. While the microorganisms are damaging the alveoli, other alveolar macrophages are being recruited to the area of inflammation. Lymphoid tissue associated with the lungs (mediastinal lymph nodes) becomes enlarged following activation of the B and T lymphocytes. Chest radiographs may show evidence of mediastinal lymph node enlargement in the patient with pneumonia.

The accumulation of microorganisms, immune cells, and serum components can cause the alveoli to fill and spread to other alveoli that are in close proximity. This inflammatory response is described as an opacity or a consolidation seen on a chest radiograph, and is often seen in patients with pneumonia caused by S pneumoniae—this type of pneumonia is called typical or lobar pneumonia. The inflammatory response to the infection and the microorganisms produce factors that allow the microorganisms to leave the lung and exert systemic effects such as fever. Examples of microbial factors that can have systemic effects include endotoxin from gram-negative bacteria resulting in fever and septic shock, and cell wall components of gram-positive bacteria that can lead to fever and septic shock.

Organisms such as M pneumoniae and the influenza virus initially do not cause a large amount of fluid to accumulate in the alveoli. However, following infection with these organisms, inflammation of the interstitial spaces (walls of the alveoli) occurs, resulting in interstitial or atypical pneumonia. Chest radiographs of patients with this type of pneumonia show fine granular diffuse infiltrates.

Other organisms such as Staphylococcus aureus, gram-negative rod-shaped bacteria, and anaerobic bacteria produce abscesses or microabscesses. In these infections the immune system can wall off the organisms and produce localized abscesses or microabscesses that usually show well-defined circular lesions with necrotic translucent centers on chest radiographs.

VAP- The endotracheal tube bypasses most of the host defenses that prevent aspiration of organisms into the lungs. In critically ill patients the oropharyngeal flora is replaced by pathogenic bacteria. Factors important in causing this change in the oropharyngeal flora are: antibiotic selection pressure, cross-infection from other infected/colonized patients, contaminated equipment, and malnutrition. Due to factors yet to be identified in around one third of patients that are mechanically ventilated the lower respiratory tract defenses are overwhelmed and allow pathogenic bacteria to infect the lungs. In severely ill patients that are mechanically ventilated it appears that they go through a period of immunosuppression after admission to the ICU. Recent studies suggest that hyperglycemia maybe be one factor causing this immunosuppression. Keeping the patients’ blood sugar close to normal with exogenous insulin may be beneficial. More frequent transfusions with leukocyte-depleted RBC’s may also positively affect the immune response of patients on a mechanical ventilator.

Diagnosis

Patients with CAP and HCAP

Patients with pneumonia may present with chest discomfort, cough (productive or nonproductive paroxysmal cough), rigors (patients with typical pneumonia) or chills (patients with interstitial pneumonia), shortness of breath, and fever. Physical examination may reveal increases in respiratory rate and heart rate and dullness to percussion over affected regions of the lungs and rales.

Chest radiographs showing new consolidations or infiltrates are definitive in helping to establish a diagnosis of pneumonia. When alveolar sacs fill with inflammatory cells and fluid, the chest radiograph will show consolidated well-defined densities that are unilateral (inhalation or aspiration pneumonia), bilateral (hematogenous spread to lungs), localized, or uniform. When a chest radiograph shows inflammation and thickening of the alveolar septa that surround the alveoli, rather than a filling of the alveolar sacs with inflammatory material, the diagnosis is more likely to be an atypical (interstitial) pneumonia.

Some organisms form abscesses in the lung (e.g., Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobic organisms) and in such cases, a chest radiograph is useful in revealing abscess formation. If present, certain classic radiologic patterns may be of diagnostic value; for example,

To identify the specific pathogen that is causing the pneumonia, clinical and epidemiologic data must be considered to limit the number of possible causes of the pneumonia (see Tables LRI-1 through LRI-7, and TablesLRI-8 and LRI-9).

Gram stain and appearance (Table LRI-10) of sputum from a patient with suspected pneumonia can be helpful in presumptive determination of the cause of the pneumonia. Some pathogens Gram stain poorly or don’t Gram stain, and if pneumonia is caused by one of the suspected pathogens, Dieterle silver stain (Legionella sp.), acid fast stain (Mycobacteria), or Gomori methenamine silver stain (fungi and Pneumocystis) should be ordered.

Additional laboratory tests that can aid in establishing a definitive diagnosis

Patient with VAP

Diagnosis of these patients can be difficult because:

There is still much debate concerning how to determine if a mechanically ventilated patient has VAP. There are now two approaches: the quantitative culture approach and the clinical approach.

Quantitative culture approach tries to discriminate between bacterial colonization and true bacterial infection by determining the bacterial burden. The respiratory tree can be sampled at various points; endotracheal aspirates and bronchoscopy. A quantitative endotracheal aspirate would be positive for bacterial colonization if the colony forming units (CFU) were less than 106 CFU/ml. If greater than 106 CFU/ml then the patient would have a VAP. If a bronchoscope was used to get a protected brush specimen to sample further down in the lungs then a CFU less than 103 CFU/ml would indicate the patient is only colonized. However, if the CFU from the protect brush specimen were greater than 103 CFU/ml then the patient has VAP. One important point to remember is that these samples should be obtained BEFORE antibiotic therapy has begun. If not false negative samples are more likely. The cultures can then also be used to identify the pathogen and determine its sensitivity to antimicrobial agents.

Clinical approach uses a Clinical Pulmonary Infection Score (CPIS) to determine if a patient is more likely to have VAP. The clinical criteria used are weighted and added together to produce a final score. A maximum score is 12 when the tracheal aspirate data arrives. A score of 6 or greater indicates the patient has VAP. Clinical criteria used are fever, leukocytosis, oxygenation, chest radiograph, and tracheal aspirates. It is not important for you to memorize this scoring procedure for the exam!

Some medical facilities utilize both approaches for diagnosis of VAP. The clinical approach is used to quickly determine if a protected brush specimen should be used to do quantitative cultures.

Treatment and Prevention

Except for patients with CAP admitted to the ICU no data exists to show that treatment directed to a specific pathogen is statistically superior to empirical therapy. Therefore, most CAP patients are treated empirically (see below for CAP and HCAP). Because most cases of pneumonias are caused by bacteria, treatment usually involves antibiotic therapy. In about one half of pneumonia patients, the etiologic agent can be determined and if the agent is known, more definitive therapy can be initiated.

CAP

HCAP (includes HAP and VAP)

*Risk factors include: hospitalization for ≥48 hours, hospitalization for ≥2 days in the prior 3 months, residence in an extended-care or nursing home facility, antibiotic therapy in preceding 3 months, chronic dialysis, home infusion therapy, home wound care, or family member with MDR infection.

There are two vaccines that can be given to adults to help prevent pneumonia. The S pneumoniae vaccine contains 23 capsular types of the bacterial capsule and is used in persons older than age 65. The influenza vaccine should be given yearly to all persons older than age 65 to help prevent viral pneumonia or secondary bacterial pneumonia that may occur following infection with the influenza virus. Chemoprophylaxis to prevent influenza infections is helpful in preventing secondary bacterial pneumonia.

The conjugated S pneumoniae 13-valent conjugate vaccine is important in preventing infection with this organism in young children. The conjugated H influenzae type b (Hib) vaccine prevents childhood infections with H influenzae. Respiratory syncytial virus infections can be prevented in premature infants, neutropenic infants, or in infants with various comorbidities with a periodic injection of respiratory syncytial virus immune globulin or humanized mouse monoclonal antibody (palivizumab). Annual immunization of children with the influenza vaccine prevents influenza infections in vaccinated children and appears to prevent spread of the virus to close contacts that may be at high risk for adverse outcomes following this viral infection.