Pneumonia (inflammation of the lower respiratory tract involving the lung’s airways and supporting structures) is a major cause of illness and death. There are two major categories of pneumonias: those considered community acquired pneumonia (patients are believed to have acquired their infection outside the hospital setting) and those including hospital- or ventilator-associated (patients are believed to have acquired their infection within the hospital setting, usually at least 2 days following admission) or health care–associated pneumonia (affects only patients hospitalized in an acute care hospital for 2 or more days within 90 days of infection from a long-term care facility, or patients who have received recent intra venous antibiotic therapy, chemotherapy, or wound care within 30 days of the current infection, or who have attended a hospital or hemolysis clinic). Nevertheless, once a microorganism has successfully invaded the lung, disease can follow affecting the alveolar spaces and their supporting structure, the interstitium, and the terminal bronchioles.

Pathogenesis

 Organisms can cause infection of the lung by four possible routes: by upper airway colonization or infection that subsequently extends into the lung, by aspiration of organisms (thereby avoiding the upper airway defenses), by inhalation of airborne droplets containing the organ ism, or by seeding of the lung via the blood from a distant site of infection. Viruses cause primary infections of the respiratory tract, as well as inhibit host defenses that, in turn, can lead to a secondary bacterial infection. For example, viruses may destroy respiratory epithelium and disrupt normal ciliary activity. Presumably, the growth of viruses in host cells disrupts the function of the latter and encourages the influx of nonspecific immune effector cells exacerbating the damage. Damage to host epithelial tissue by virus infection is known to predispose patients to secondary bacterial infection.

Aspiration of oropharyngeal contents is important in the pathogenesis of many types of pneumonia. Aspiration may occur during a loss of consciousness such as during anesthesia or a seizure, or after alcohol or drug abuse, but other individuals, particularly geriatric patients, may also develop aspiration pneumonia. Neurologic disease or esophageal pathology and periodontal disease or gingivitis are other important risk factors. Aided by gravity and often by loss of some host nonspecific protective mechanisms, organisms reach lung tissue, where they multiply and attract host inflammatory cells. Other mechanisms include inhalation of aerosolized material and hematogenous seeding. The buildup of cell debris and fluid contributes to the loss of lung function and thus to the pathology.

Furthermore, regarding the pathogenesis of hospital associated, health care–associated, and ventilator associated pneumonias, health care devices, the environment, and the transfer between the patient and staff or other patients can serve as sources of pathogens causing pneumonia. The primary routes for bacterial entry into the lower respiratory tract are by aspiration of oropharyngeal organisms or leakage of secretions containing bacteria around an endotracheal tube. For these reasons, intubation and mechanical ventilation significantly increase the risk of pneumonia (6- to 21-fold). In addition, bacterial and viral biofilm in the endotracheal tube with subsequent spread to distal airways may be important in the pathogenesis of ventilator-associated pneumonia.

Clinical Manifestations

The symptoms suggestive of pneumonia include fever, chills, chest pain, and cough. In the past, pneumonias were classified into two major groups: (1) typical or acute pneumonias (e.g., Streptococcus pneumoniae) and (2) atypical pneumonias, based on whether the cough was productive or nonproductive of mucoid sputum. However, analysis of symptoms of pneumonia caused by the atypical pneumonia pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae) has revealed no significant differences from those symptoms of patients with typical bacterial pneumonias. Because of this overlap in symptoms, it is important to consider all possible etiologies associated with the patient’s clinical presentation.

Some patients with pneumonia exhibit no signs or symptoms related to their respiratory tract (i.e., some only have fever). Therefore, physical examination of the patient, chest radiograph findings, patient history, and clinical laboratory findings are important. In addition to respiratory symptoms, 10% to 30% of patients with pneumonia complain of headache, nausea, vomiting, abdominal pain, diarrhea, and myalgias.

Epidemiology/Etiologic Agents

As previously mentioned, there are two major categories of pneumonias: those considered community-acquired pneumonias and hospital-, ventilator-, or health care associated pneumonias. Because the epidemiology and etiologies can differ, these two categories are discussed separately. Pneumonia in the immunocompromised patient is addressed separately in this chapter. Emerging viral infections associated with severe acute respiratory syndrome (SARS) and influenza outbreaks (H1N1) are typically associated with upper respiratory infections but may lead to serious lower respiratory infections in the young, elderly, or immunocompromised patient.

Community-Acquired Pneumonia. In the United States, pneumonia is the sixth leading cause of death and the number one cause of death from infectious diseases. It is estimated that as many as 2 million to 3 million cases of community-acquired pneumonia occur annually, and roughly one fifth of these require hospitalization; 45,000 pneumonia-related deaths occur in the United States each year. The etiology of acute pneumonias is strongly dependent on age. More than 80% of pneumonias in infants and children are caused by viruses, compared to less than 10% to 20% of pneumonias in adults.

Children. Community-acquired pneumonia in children is a common and potentially serious infection. The annual incidence of pneumonia in children younger than 5 years of age is 34 to 40 cases per 1000 in Europe and North America. Determining the cause of pneumonia is challenging because the lungs are rarely sampled directly and sputum is difficult to obtain from children. Among previously healthy patients 2 months to 5 years old, RSV, human metapneumovirus, parainfluenza, influenza, and adenoviruses are the most common etiologic agents of lower respiratory tract disease. Children suffer less commonly from bacterial pneumonia, usually caused by H. influenzae, S. pneumoniae, or S. aureus. Neonates may acquire lower respiratory tract infections with C. trachomatis or P. jiroveci (which likely indicates an immature immune system or an underlying immune defect).

M. pneumoniae and C. pneumoniae are the most common causes of bacterial pneumonia in school-age children (5-14 years of age). The four most common causes of community-acquired viral pneumonia in children include influenza, RSV, parainfluenza, and adenovirus. The agents associated with nosocomial outbreaks in children include the influenza virus, RSV, and adenovirus. Mixed viral and bacterial infections have been documented in 35% of patients, with the majority of these (81%) being mixed viral-bacterial infections. In addition, the time of onset of hospital- or ventilator-associated pneumonia is an important epidemiologic variable and risk factor: early-onset pneumonia (defined as occurring within the first 4 days of hospitalization), usually carries a better prognosis, being more likely to be caused by antibiotic sensitive bacteria, whereas late-onset pneumonia (5 days or more) is more likely to be caused by multidrug-resistant organisms and is associated with increased patient morbidity and mortality.

Young Adults. The most common etiologic agent of lower respiratory tract infection among adults younger than 30 years of age is Mycoplasma pneumoniae, which is transmitted via close contact. Contact with secretions seems to be more important than inhalation of aerosols for transmission and infection. After contact with respiratory mucosa, Mycoplasma are able to adhere to and colonize respiratory mucosal cells. Both a protein adherence factor and gliding motility determine virulence. Mycoplasma attach to the cilia of respiratory mucosal cells; once there, they multiply and destroy ciliary function. Attachment and cytotoxins produced by the organisms induce cell damage. Chlamydia pneumoniae is the third most common agent of lower respiratory tract infection in young adults, following mycoplasmas and influenza viruses; it also affects older individuals. Chlamydia spp., intracellular pathogens capable of disrupting cellular function and causing respiratory disease, are similar to viral pathogens.

The epidemiology and treatment of community acquired and hospital-acquired pneumonia have changed dramatically as a result of improvements in diagnostics, antimicrobial therapy, and supportive care modalities. The changes in the organization of health care has made the distinction between community-acquired and hospital-acquired pneumonia less clear. However, pneumonia still remains an important cause of morbidity and mortality in elderly patients. The American Thoracic Society and the Infectious Disease Society of America guidelines have suggested that patients who have been hospitalized in the last 90 days, reside in a nursing home or long-term care facility, or have had a recent intravenous antibiotic therapy or hemodialysis, be classified as a patient with health care-associated pneumonia (HCAP). Patients with health care-associated pneumonia have a higher incidence of cardiopulmonary and neurodegenerative dis eases, cancer, chronic kidney disease, chronic obstructive pulmonary disease, and immunosuppression than elderly patients with community-acquired pneumonia. Both populations become infested with various organisms. The organisms most frequently responsible for community-acquired pneumonia include S. pneumoniae, H. influenzae, M. pneumoniae, C. pneumoniae, M. catarrhalis, and Legionella spp. Factors that contribute to the onset include decreased mucociliary function, decreased cough reflex, decreased level of consciousness, periodontal disease, and decreased general mobility. Health care-associated patients have been found to be more frequently colonized with gram-negative bacilli and other multidrug resistant pathogens, perhaps because of poor oral hygiene, decreased saliva, or decreased epithelial cell turnover. The microorganisms associated with these infections, in addition to those previously mentioned, may include methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, a variety of Enterobacteriaceae, Acinetobacter spp., anaerobic bacteria, carbapenamase-resistant Klebsiella pneumonia, and extended spectrum beta-lactamase resistant Enterobacteriaceae (ESBLS). According to the Infectious Diseases Society of America (IDSA), the decision to hospitalize a patient or to treat him or her as an outpatient is possibly the single most important clinical decision made by physicians during the course of illness. This decision in turn impacts the subsequent site of treatment (home, hospital, or intensive care unit), intensity of laboratory evaluation, antibiotic therapy, and cost. Thus, the IDSA has developed management guidelines for community-acquired pneumonia in adults based on a three-step process: (1) assessment of preexisting conditions that might compromise safety of home care, (2) quantification of short-term mortality (referred to as the pneumonia port severity index [PSI] and based on a prediction rule derived from more than 14,000 patients) with subsequent assignment of patients to five risk classes (classes I through V), and (3) clinical judgment usually require hospitalization. The PSI, however, is not useful for patients in nursing homes or other health care facilities. It is therefore essential to properly assess the severity of the disease in both cases of community-acquired and health care associated pneumonia in elderly patients that clearly includes the three major management guidelines as outlined by the IDSA.

Pneumonia secondary to aspiration of gastric or oral sections is common and occurs in the community setting.

Pneumonia secondary to aspiration of gastric or oral secretions is common and occurs in the community setting. The most common agents include the oral anaerobes such as black-pigmented Prevotella and Porphyromonas spp., Prevotellaoris, P. buccae, P. disiens, Bacteroides gracilis, fusobacteria, and anaerobic or microaerophilic streptococci. The anaerobic agents possess many factors, such as extracellular enzymes and capsules enhancing their ability to produce disease. It is their presence, however, in an abnormal site within the host producing lowered oxidation-reduction potential secondary to tissue damage that contributes to their pathogenicity. Staphylococcus aureus, various Enterobacteriaceae, and Pseudomonas may also be acquired by aspiration; Haemophilus influenzae, Legionella spp., Acinetobacter, Moraxella catarrhalis, Chlamydia pneumoniae, meningococci, and other agents may also be implicated. Pnuemonia is the leading cause of death among patients with nosocomial infections (hospital- ventilator- and health care-associated) (as high as 50%) mortality among patients in intensive care units. Some of these pneumonias are secondary to sepsis, and some are related to contaminated inhalation therapy equipment, particularly for intubated patients. Hospitalized patients or long-term care patients may experience asymptomatic colonization of the upper airway and result in aspiration of microorganisms into the lower respiratory tract. In addition to those organisms previously listed, these patients are more prone to infections with the multi-drug resistant strains of bacteria (ESBLS and MRSA) including Providencia stuartii, Morganella morganii, E. coli, Proteus mirabilis, K. pneumoniae, Enterobacter spp., and Staphylococcus aureus.

Adults (Viral pneumonia). Adults may suffer from an estimated 100 million cases annually of community-acquired viral pneumonia cased by influenza, adenovirus, enteroviruses (coxsackieviruses and rhinoviruses), coronaviruses, human metapneumovirus, parainfluenza, varicella, rubeola or RSV, particularly during epidemics. Influenza associated viral pneumonia poses an increased risk for pregnant women of approximately 4-9 times greater than the general public, with the greatest risk associated with the third trimester. RSV is considered the third most common cause of community-acquired pneumoniae with 78% of the deaths occurring in patients over the age of 65. Similarly to RSV, human metapneumovirus has been associated with outbreaks in long-term care facilities. Following viral pneumonia, secondary bacterial disease caused by beta-hemolytic streptococci, S. aureus, M. catarrhalis, H. influenzae, and Chlamydia pneumoniae. Other agents may be considered depending on the geographic location and clinical presentation are viruses in the Hantavirus group, the most common of which is sin nombre virus as well as severe acute respiratory syndrome (SARS.

Of these agents, influenza virus, RSV and adenovirus have been implicated in nosocomial outbreaks. The time of onset of hospital- or ventilator-associated pneumonia is an important epidemiologic variable and risk factor; early onset pneumonia (defined as occurring within the first 4 days of hospitalization.

Adults (Fungal pneumonia). Unusual causes of acute lower respiratory tract infection in adults include Actinomyces and Nocardia spp. Other agents may rarely be recovered from sputum and include the agents of plague, tularemia, melioidosis (Burkholderia pseudomallei), Brucella, Salmonella, Coxiella burnetii (Q fever), Bacillus anthracis, Pasteurella multocida, and certain parasitic agents such as Paragonimus westermani, Entamoeba histolytica, Ascaris lumbricoides, and Strongyloides spp. (the latter may cause fatal disease in immunosuppressed patients). A high index of suspicion by the clinician is usually a pre requisite to a diagnosis of parasitic pneumonia in the United States. Psittacosis should be ruled out as a cause of acute lower respiratory tract infection in patients who have had recent contact with birds. Among the fungal etiologies, Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Coccidioides immitis, Cryptococcus neoformans, and, occasionally, Aspergillus fumigatus may cause acute pneumonia. Therefore, occupational history and history of exposure to animals are important in suggesting specific potential infectious agents.

Chronic Lower Respiratory Tract Infections. Mycobacterium tuberculosis is the most likely etiologic agent of chronic lower respiratory tract infection, but fungal infection and anaerobic pleuropulmonary infection may also run a subacute or chronic course. Mycobacteria other than M. tuberculosis may also cause such disease, particularly M. avium complex and M. kansasii. Although possible causes of acute, community-acquired lower respiratory tract infections, fungi and parasites are more commonly isolated from patients with chronic disease. Actinomyces and Nocardia may also be associated with gradual onset of symptoms. Actinomyces is usually associated with an infection of the pleura or chest wall, and Nocardia may be isolated along with an infection caused by M. tuberculosis. The pathogenesis of many of the infections caused by agents of chronic lower respiratory tract disease is characterized by the requirement for breakdown of cell mediated immunity in the host or the ability of these agents to avoid being destroyed by host cell-mediated immune mechanisms. This may be caused by an effect on macrophages, the ability to mask foreign antigens, sheer size, or some other factor, allowing microbes to grow within host tissues without eliciting an overwhelming local immune reaction.

Cystic fibrosis (CF) is a genetic disorder that leads to persistent bacterial infection in the lung, causing airway wall damage and chronic obstructive lung disease. Eventually, a combination of airway secretions and damage leads to poor gas exchange in the lungs, cardiac malfunction, and subsequent death. Patients with CF may present as young adults with chronic respiratory tract disease or, more commonly, as children with gastrointestinal problems and stunted growth. Staphylococcus aureus is the most prevalent opportunistic bacterial pathogen infecting 55% of children 0–9 years of age with CF, with Pseudomonas aeruginosa the most prevalent (81%) in older children. A very mucoid Pseudomonas, characterized by production of copious amounts of extracellular capsular polysaccharide, can be isolated from the sputum of almost all patients with CF who are older than 18 years of age, becoming more prevalent with increasing age after 5 years. Even if CF has not been diagnosed, isolation of a mucoid Pseudomonas aeruginosa from sputum should alert the clinician to the possibility of underlying disease. Microbiologists should always report this unusual morphologic feature. In addition to mucoid Pseudomonas and Staphylococcus aureus, important pathogens in patients with CF are likely to harbor Haemophilus influenzae, Streptococcus pneumoniae, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Ralsotnia spp. Cupriavidus spp., Pandoraea spp., Escherichia coli, strains of Burkholderia cepacia complex, fast growing mycobacteria, RSV, influenza and fungi including Aspergillu, Scedosporium spp., and Exophiala dermatidis. In addition, due to the viscous mucous plugs associated with CF, several anaerobic organisms have been detected in the lungs of CF patients including Prevotella, Bifidobacterium, Veillonella, Peptostreptococcus and Fusobacterium. Using advanced diagnostic molecular methods, additional organisms have also been identified in chronic polymicrobial CF infections including viridans streptococci, Streptococcus constellatus, Streptococcus intermedius and Streptococcus anginosus.

Lung abscess is usually a complication of acute or chronic pneumonia. In these circumstances, organisms infecting the lung cause localized destruction of the lung parenchyma (functional elements of the lung). Symp toms associated with lung abscess are similar to those of acute and chronic pneumonia, except symptoms fail to resolve with treatment.

Immunocompromised Patients. Patients with Neoplasms. Patients with cancer are at high risk to become infected because of either granulocytopenia or other defects in phagocytic defenses, cellular or humoral immune dysfunction, damage to mucosal surfaces and the skin, and various medical procedures such as blood product transfusion. In these patients, the nature of the malignancy often determines the etiology (Table 1) and pneumonia is a frequent clinical manifestation.

Table1. Examples of Infectious Agents Frequently  Associated with Certain Malignancies

Transplant Recipients. For successful organ transplantation, the recipient’s immune system must be suppressed. As a result, these patients are predisposed to infection. Regardless of the type of organ transplant (heart, renal, bone marrow, heart/lung, liver, pancreas), most infections occur within 4 months following trans plantation. Major infections can occur within the first month but are usually associated with infections carried over from the pretransplant period. Pulmonary infections are of great importance in this patient population. Some of the most common causes of pneumonia include S. aureus Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis jiroveci, and cytomegalovirus. In addition, other organisms such as Cryptococcus neoformans, Aspergillus spp., Candida spp., Nocardia sp. and over, can cause life-threatening pulmonary infection.

HIV-Infected Patients. Patients who are infected with human immunodeficiency virus (HIV) are at high risk for developing pneumonia. As discussed in the previous chapter, opportunistic infections as a result of severe immunodeficiency are a major cause of illness and death among these patients. In the United States, the most common opportunistic infection among patients with acquired immunodeficiency syndrome is Pneumocystis jiroveci pneumonia. Although P. jiroveci remains a major pulmonary pathogen, other organisms must be considered in this patient population, including Mycobacterium tuberculosis and Mycobacterium avium complex, as well as common bacterial pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. In addition to these common pathogens, many other organisms can cause lower respiratory tract infections, including Nocardia spp., Rhodococcus equi (a gram-positive, aerobic, pleomorphic organism), and Legionella spp.

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Pathogenesis of the respiratory tract: Host Factors

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Definition of Sepsis

Types of Bloodstream Infections

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Alzheimer’s Disease

Human Prion Diseases

Diabetes treatments

Preeclampsia and Eclampsia

Gestational Diabetes