Epidemiology Etiologic Agents

As previously mentioned, there are two major categories of pneumonias: those that are considered community-acquired and those considered hospital-, ventilator- or healthcare-associated. Because the epidemiology and etiologies can somewhat differ, these two major categories are discussed separately. Because of the many potential etiologic agents, pneumonia in the immunocompromised patient is addressed separately in this chapter.

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 to 3 million cases of community-acquired pneumonia occur annually and roughly one fifth of these require hospitalization; 45,000 deaths occur in the United States each year.2 The etiology of acute pneumonias is strongly dependent on age. More than 80% of pneumonias in infants and children are caused by viruses, whereas less than 10% to 20% of pneumonias in adults are viral

Children. Community-acquired pneumonia is a common and potentially serious infection that afflicts children. 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.18 Determining the cause of pneumonia is challenging because the lung is rarely sampled directly and sputum can rarely be obtained from children. Among previously healthy patients 2 months to 5 years old, RSV, human meta-pneumovirus, 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. infbm-

zae, 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 to 14 yean of age). Recently, a study confirmed the high prevalence of viral pneumonia in this age group30; the most common viruses, rhinovirus, adenovirus, parainfluenza viruses, influenza virus, and RSV were detected in 45%, 12%, 8%. 7%, and 3% of patients, respectively. Of note, mixed infections were documented in 35% of patients, with the majority of these (81%) being mixed viral-bacterial infections. However, it is not clear what these multiple microbial associations mean.

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 dose contact. Contact with secretions seems to be more important than inhalation of aerosols for becoming infected. After contact with respiratory mucosa, Mycoplasma organisms are able to adhere to and colonize respiratory mucosal cells. Both a protein adherence factor and gliding motility may be virulence determinants. Once situated in their preferred site between the cilia of respiratory mucosal cells, Mycoplasma organisms multiply and somehow destroy ciliary function. Cytotoxins produced by Mycoplasma organisms may account for the cell damage they inflict. Chtarny-daphila pneumoniae (originally called Chlamydia TWAR or Chlamydia pneumoniae) is the third most common agent of lower respiratory tract infection in young adults, after mycoplasmas and influenza viruses; it also affects older individuals.11" Chlamydiae are intracellular pathogens, thus their ability to disrupt cellular function and cause respiratory disease is similar to that of viruses.

Adults. In recent years, the epidemiology and treatment of community-acquired pneumonia has changed.2,21 From 1979 through 1994, the ovmll rates of death due to pneumonia and influenza increased by 59%.21'"Pneumonia is increasing among older patients and those with underlying diseases such as chronic obstructive lung disease and diabetes mellitus. These patients may become infected with various organisms, including newly identified or previously unrecognized pathogens. Factors such as decreased mucodliary function, decreased cough reflex, decreased level of cons-dousness, periodontal disease, and decreased general mobility probably contribute to a greater inddence of pneumonia in older patients. Such patients have been found to be more frequendy colonized with gramnegative bacilli than younger people, perhaps because of poor oral hygiene, decreased saliva, or decreased epithelial ceB turnover.

Although mortality in the outpatient setting remains low (about 1%), mortality rates for community-acquired pneumonia approximate 25% if the patient requires hospitalization.216'17 In addition, the epidemiology and distribution of etiologic agents in patients with severe community-acquired pneumonia who require hospitalization differs somewhat from patients with pneumonia who do not require hospitalization. According to the Infectious Diseases Sodety of America (IDSA), the derision to hospitalize a patient or to treat them as an outpatient is possibly the single most important clinical derision made by physidans during the course of illness;*'15 This dedsion in turn impacts the subsequent site of treatment (home, hospital floor, or hospital intensive care unit), intensity of laboratory evaluation, antibiotic therapy, and cost. Thus, management guidelines for community-acquired pneumonia in adults were developed by the IDSA 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 dasses (classes I through V), and (3) clinical judgment. In general, patients stratified to risk classes IV and V usually require hospitalization. Other guidelines have been set forth that differ from one another.15 Future guidelines are being investigated in a joint effort by the IDSA and the American Thoradc Sodety.

Community-acquired pneumonia in adults is most commonly due to bacterial infections. Regardless of age or coexisting illness, Streptococcus pneumoniae is most prevalent, causing 15% to 80% of all community-acquired bacterial pneumonia. Additional common etiologies for those patients who are not hospitalized and those who are hospitalized are listed in Tables 53-2 and 53-3, respectively.

Pneumonia secondary to aspiration of gastric or oral secretions is common and occurs in the community setting. The most common agents are primarily the oral anaerobes such as black-pigmented Pmotella and Porphyromonas spp., Prevotella oris: P. buccae, P. disims.Bac-teroides gracilis, fusobacteria, and anaerobic and micro-aerophilic streptococd. The anaerobic agents possess many factors, such as extracellular enzymes and capsules that may enhance 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 most to their pathogenidty. Staphylococcus aureus, various Ente-robacteriaceae, and Pseudomonas may also be acquired by aspiration; Haemophilus influenzae, Legionella spp"

Table 53-2 Most Common Etiologies of Community-Acquired Pneumonia in Adults Who Are Not Hospitalized

Age

Coexisting illness

Most Common Etiologies*

sGOyrs

No

M. pneumoniae, respiratory viruses, C. pneumoniae, H. influenzae

>60yrs

Yes

Respiratory viruses, H. influenzae, aerobic gram-negative rods, Staphylococcus aureus

'Streptococcus pneumonias is the most common etiology for atf categories of adult patients with pneumonia.

Table S3-3 Most Common Etiologies of Community-Acquired Pneumonia in Adults Who Are Hospitalized

Acinetobarter, Moraxella catarrhal, Chlamydophila pneumoniaeā€˛ meningococci and other agents may also be implicated.

Adults also may suffer from viral pneumonia caused by influenza, adenovirus, cytomegalovirus, parainfluenza, varicella, rubeola, orRSV, particularly during epidemics. After viral pneumonia, especially influenza, secondary bacterial disease caused by beta-hemolytic streptococci, pneumococq. Staphylococcus aureus, Moraxella catarrhal, Haemophilus influenzae, and Chlamydo-phila pneumoniae is more likely. Other agents that might be considered depending on geographic location and clinical presentation are viruses in the Hantavirus genus, the most common of which is sin nombre virus as well as severe acute respiratory syndrome (SARS) (see Chapter 51).

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 anthrads, Pasteurella multodda, and certain parasitic agents such as Paragonimus wes-termani. Entamoeba histolytica, Ascaris lumbricoides, and

Generally Requiring Intensive Care Unit

Most Common Etiologies* -

No

H. influenzae; polymicrobial, aerobic gram-negative bacilli; Legionella spp.; Staphylococcus aureus; C. pneumoniae; respiratory viruses

Yes

Legionella spp., aerobic gram-negative bacilli, M. pneumoniae, respiratory viruses

'Streptococcus pneumoniae Is the most common etiology for a//categories of adult patients hospitalized with pneumonia.

Strongyloides spp. (the latter may cause fatal disease in hnmunosuppressed patients). A high index of suspicion by the clinician is usually a prerequisite 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 brasi-liertsis, Qmdioides immitis, Ctyptococcus neoformans, and, occasionally, Aspergillusfitmigatus may cause acute pneumonia. Therefore, occupational history and history of exposure to animals are important in suggesting specific potential infectious agents.

Hospital-, Ventilator-, and Healthcare-Associated Pneumonia. Pneumonia is the leading cause of death among patients with nosocomial infections (as high as 50% mortality among patients in intensive care units).28 Some of these pneumonias are secondary to sepsis, and some are related to contaminated inhalation therapy equipment.

Nosocomial pneumonia is a risk for any hospitalized patient, particularly for intubated patients. Organisms associated with these infections can be hospital-specific, but overall the most common include P, aeruginosa, Enterobacter spp., Klebsiella spp., other Bnterobacteria-ceae, S. aureus (with methicillin-resistant strains rapidly emerging), Adnetobacter spp., S. pneumoniae, anaerobes, Legionella, and H. influenzaeP Other agents have been associated with nosocomial outbreaks, including influenza virus. Viruses, such as RSV, adenovirus, and influenza A, are often implicated as causes of nosocomial pneumonia among hospitalized children. 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.1

Aspiration pneumonia with infection caused by gram-negative bacilli or staphylococci is probably the major type of hospital-acquired pneumonia, followed by pneumococcal disease. Legionella has been implicated in a number of hospital outbreaks, but the problem is typically specific to a given institution.

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-intracellulare and M, kamstu 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 usuaUy 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 some breakdown of cell-mediated immunity m Ore host or die 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 secrettons 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 the more common presentation is in children who may also present with gastrointestinal problems and stunted growth. 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 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 such an underlying disease. Microbiologists should always report this unusual morphologic feature if it is encountered. In addition to mucoid Pseudomonas, patients with CF are likely to harbor Staphylococcus aureus, Haemophilus influenzae, and Burkhoideria cepacia complex. RSV, influenza A, nontuber-culous mycobacteria, and Aspergillus are also important pathogens in this population.

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). Symptoms 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 gran ulocytopenia and/or other defects in phagocyuc de fenses cellular andfor 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 53-4) and pneumonia is a frequent clinical manifestation.

Transplant Recipients. For successful organ trans plantation, the recipient's immune system must be suppressed in some fashion. For this reason, these patterns are predisposed to infection. Regardless of the type of organ transplant (heart, renal, bone marrow, hean / lung, liver, pancreas), most infections occur wrthin 4 months following transplantation. Major infections can occur within the first month but are usually associated with infections carried over from the pre-transplant period. Pulmonary infections are of great importance in this patient population, Some of the most common causes of pneumonia include Streptococcus pneumoniae, Haemophilus influenzae, Pneumocysus proved, and cytomegalovirus. Of importance, fungi, such as Cryptocoecus neoformans, Aspergillus spp. Candida spp., and zygomycetes, 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 jimeci pneumonia. Although P- Jinvea 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, m addition to these common pathogens, many other organisms can cause lower respiratory tract infections, including Nocardia spp., Khodococcus equi (a gram-positive, aerobic, pleomorphic organism), and Legionella spp.

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