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Health Articles

Tuberculosis

21st June 2007

Tuberculosis

An infectious disease caused by Mycobacterium tuberculosis.
Remarkable progress has been made in the control of tuberculosis (TB) in the USA and other industrialized countries. The mortality rate for TB patients declined from about 200/100,000 population at the turn of the century to about 1.5/100.000 in the 1980s. However, since 1985 this steady downward trend has reversed, and the number of active cases of TB is now increasing in the USA. This increase is attributed largely but not exclusively to the AIDS epidemic. In addition, the number of cases involving multidrug-resistant strains is increasing alarmingly. Persons > 65 yr account for 25% lo 30% of newly diagnosed TB cases. The reasons are threefold: (1) Many older persons became infected when the prevalence of TB was substantially higher, (2) The loss of cell-mediated immunity that accompanies aging favors reactivation of dormant foci. (3) Prolonged conlacl with a large number of susceptible hosts, as occurs in chronic-care facilities, favors person-to-person spread.
Pathogenesis
Tuberculosis infection is acquired by inhaling droplet nuclei containing microorganisms aerosolized from untreated persons. The risk of transmission is remarkably lower once treatment has begun, even when sputum cultures continue to yield the microbe. Also, the duration of contact is important. Under ordinary circumstances, sustained exposure for at least 2 mo is required to achieve the inoculum necessary for transmission.
The inhaled organisms are deposited in the alveoli, most commonly in the lower lobes, which arc the best-ventilaled portions of the lung. There the organisms replicate slowly, about once every 24 h. They gain access to lymphatic channels, involving Ihe regional lymph nodes in the chest, and then pass through the thoracic duct to the bloodstream, where widespread hematogenous dissemination may occur.
With the initial infection, known as primary TB, the patient may have a bronchopneumonia, usually involving the lower lobes and often the regional lymph nodes, or a unilateral pleural effusion. More frequently, Ihe patient remains asymptomatic and the infection is detected later by a positive skin test, sometimes associated with x-ray changes that usually consist of a solitary nodule or a nodule accompanied by hilar adenopathy (Ghon complex). The nodule is often calcified, which helps distinguish it from carcinoma.
Patients with positive skin tests generally harbor viable organisms within macrophages, and they can retain a balanced host-parasite relationship for decades. Most TB cases in elderly patients involve reactivation of dormant organisms and are referred lo as reactivation TB. Reactivation TB tends to occur at sites with relatively high oxygen concentrations, presumably because the organism is an obligate aerobe. A typical site is the lung’s upper lobe, where ventilation-pcrfusion ratios provide high oxygen concentrations. Even so. elderly people (especially those in nursing homes) often express TB as a pneumonitis in the lungs’ lower and middle portions.
Reactivation usually occurs when immune defenses, primarily cell-mediated immunity, are compromised (sec Ch. 84). Cell-mediated immunity appears to be the most important factor in a balanced host-parasite relationship, and immunity is often compromised as the thymus atrophies with aging. By the fifth decade, a person has minimal thymic tissue, although lymphocytes and monocytes capable of antigenic recall continue to circulate for two to three more decades. Standard skin tests for cell-mediated immunity reveal a relatively high rate of anergy in the elderly. Despite this loss, most elderly patients are not more susceptible to the pathogens associated with other conditions characterized by anergy, such as immunosuppression from corticosteroid therapy, cancer chemotherapy, lymphomas, or AIDS. Rather, TB appears to be the exception.
Symptoms and Signs
Because TB in the elderly is often subtle, many of the clinical complaints, including weight loss, cough, weakness, and dyspnea, may be attributed to other conditions or even to aging itself. Fever is generally low grade and may not be apparent to the patient unless the temperature is measured. Night sweats and hemoptysis, which specifically suggest TB, are often not present or not pursued.
Diagnosis
The major diagnostic studies are the skin test, chest x-ray, and sputum culture. Because chest x-ray findings may be atypical, some authorities recommend that any elderly person who requires hospitalization for pneumonitis have at least one sputum culture for TB. All new employees and new residents in chronic-care facilities should have routine skin tests and chest x-rays; skin tests should usually be repeated annually.
Skin test: The preferred skin test is performed by injecting 5 tuberculin units of 0.1 mL purified protein derivative (PPD) into the volar or dorsal skin of the forearm. Results should be measured on Ihe second or third day. The size of the reaction correlates to some extent with the probability of TB; induration of 3: 10 mm is significant. A smaller reaction (5 to 10 mm of induration) is suspect in high-risk populations. BCG vaccine given in childhood does not account for a positive PPD skin test decades later.
Since reactivity wanes with time, a test lhal produces a negative result in the elderly should be repeated (using the same dose) a week later to delect the booster phenomenon. Most patients with active TB have positive tests, although some are anergic to all skin test reagents. A small percentage with active disease are selectively anergic only to tuberculin. The second-strength (250 tuberculin units) PPD lest should not be used, and patients with a history of a positive test should not be rctesled. A positive test indicates that the person harbors viable organisms, although the test docs not distinguish dormant from active disease. This distinction is made by symptoms, chesl x-ray, and cultures.
Chest x-ray: All patients with a newly detected positive PPD test and those with anergy should have a chesl x-ray and clinical evaluation. When x-ray findings indicate TB, they should be compared with the patient’s past x-rays. The disease is considered active if symptoms and progressive changes on chest x-rays are attributed to current infection or if a culture yields M. tuberculosis.
Sputum culture: All patients suspected of having TB should have three morning sputum samples stained and cultured for acid-fast bacillus (AFB>. Sputum stains for AFB identify about half the patients who subsequently have positive cultures without cavitary disease. Most patients with cavitary disease have a large mycobacterial load and positive AFB sputum smears. Patients who cannot expectorate sputum should have sputum production induced; if this is unsuccessful, they should undergo bronchoscopy.
Prophylaxis
High-risk persons who do not have active disease should undergo preventive therapy with isoniazid, 300 mg/day orally for 6 to 12 mo. This therapy is recommended for household members and other close contacts of potentially infectious persons; for newly infected persons (those who have had a tuberculin skin lest conversion within the previous 2 yr); for persons with positive skin tests and abnormal chest x-rays compatible with previous TB; and for persons with positive skin tests in certain clinical situations, such as silicosis, diabetes, immunosuppression (including that resulting from corticosteroid administration and cancer chemotherapy), HIV-positive serologic findings, hematologic and reticuloendothelial malignancies, end-stage renal disease, and associated conditions characterized by rapid weight loss or chronic malnutrition.
Treatment
Patients with active TB require fourantiluberculous drugs: isoniazid. rifampin, pyrazinamide, and ethambutol. Treatment is given for 2 mo, until sensitivity test results are available. All M. tuberculosis isolates should undergo sensitivity testing for resistance. Patients with strains of TB sensitive to isoniazid and rifampin should receive these drugs for an additional 4 mo. Since most elderly patients acquired their original strains many decades before, when resistance was nonexistent, this treatment regimen is usually appropriate. Pyridoxine 25 to 50 mg/day is given to prevent peripheral neuropathy from isoniazid.
These recommendations are modified if in vitro sensitivity tests indicate infection with resistant strains. The current recommendation for multidrug-resistanl strains (resistant to isoniazid and rifampin) is to give two drugs that are active in vitro for at least 18 mo. Resistance is suspected in patients who have undergone previous courses of treatment (especially if compliance was poor), in those with recently acquired disease, in immigrants from areas endemic for resistant strains, and in persons who acquire the infection from contact with these sources.
All patients wilh TB should remain under observation until compliance with their treatment regimen is established. Monitoring during treatment includes baseline measurements of liver enzyme, bilirubin, and serum creatinine levels; a CBC count; and a platelet count or estimate. Serum uric acid concentration should be measured when pyrazinamide is used. Patients should be monitored for adverse reactions, with specific attention to symptoms suggesting hepatitis (eg, jaundice, fever, anorexia, and dark urine). Such monitoring is especially important in elderly patients receiving isoniazid, since the frequency of hepalitis as an adverse effect shows an age-related correlation. Patients should he seen or contacted at least monthly during treatment and specifically questioned about these symptoms.
Routine laboratory testing is not recommended if there are no symptoms, although some physicians assess liver function monthly, especially during the first 6 mo of treatment when hepatitis is most likely to occur. Transaminase levels at least three times higher than Ihe upper limit of normal values conlraindicate further isoniazid treatment. For patients with active disease, sputum should be examined at least monthly until cultures convert to negative. In about 90% of patients, cultures convert within 3 mo of initiating the recommended regimens.

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21st June 2007

Pneumonia and Tuberculosis

An inflammatory reaction to microbes or microbial products involving the pulmonary parenchyma.
Pneumonias are the most common fatal infections; they are the sixth leading cause of death by disease in the USA, and the fourth leading cause of death in the elderly. Sir William Osier referred lo pneumonia as “a special enemy of old age” in the first edition of his famous textbook, but he referred to it as “the friend of the aged” in the third edition. It is perhaps befilting that he eventually died of a lingering case of pneumonia, during which his major regret was that he “would not be able lo witness the autopsy.”
A review of 44,6X4 cases of pneumonia in Massachusetts between 1921 and 1930 showed lhatthc incidence of pneumonia increased about fivefold for patients in their 80s compared with those in their 20s. Far more striking was the nearly hundredfold increase in the mortality rate for those > 70 yr, a rate that increased about 10% for each decade after age 20. Pneumonia is found in 25% to 60% of elderly patienls at autopsy, often a late complication of another fatal condition.
The hospitalized elderly have a threefold greater incidence of nosocomial pneumonia than do younger patients. It is the most common fatal nosocomial infection in acute-care facilities and also a major problem in chronic-care facilities, where its prevalence may be as high as 50 times that in age-matched, home-based patients. The yearly incidence varies from 20/1000 to 40/1000 for community-acquired pneumonias to 100/1000 to 250/1000 for pneumonias acquired in chronic-care facilities. At any given lime, as many as 2.1% of nursing home residents may have lower respiratory tract infections.
Etiology
Because expectorated sputum is contaminated during passage through the upper airways, valid information concerning the distribution of specific pathogens is limited. In addilion. no specific pathogen is detected in 30% to 50% of cases. More reliable diagnostic specimen sources—translracheal aspirate culture, blood culture, and specific serologic tests—implicate the following microorganisms as the most common causes of pneumonia in the elderly: Streptococcus pneumoniae, gram-negative bacilli, anaerobic bacteria. Legionella pneumophila, and viruses, especially the influenza virus. Other well-eslablished but less common pulmonary pathogens in all populations are Staphylococcus aureus and Hemophilus influenzae.
The pneumocOCCUS: S. pneumoniae, also known as the pneumo-coccus, is the most common bacterial cause of community-acquired pneumonia in both older and younger persons. In most studies, S. pneumoniae accounts for 15% to 50% of all pneumonias in adults. The attack rate of pneumococcal pneumonia is estimated to be 46/1000 persons > 65 yr old. Studies based on expectorated sputum samples in community-acquired pneumonia indicate Ihat the recovery rate of II. influenzae is second only to that of .V. pneumoniae; however, interpretation is difficult because either organism may be simply an oropharyngeal contaminant. Strains of hi. influenzae account for 8% (o 20% of pneumonias. These organisms are frequently recovered from the oropharynx of patients with chronic bronchitis.
Gram-negative bacilli: These pathogens are found relatively infrequently in patients with community-acquired infection. They arc far more common in institutional settings, where Klebsiella, Pseudomonas aeruginosa. Enterobacter spp, Proteus spp, Escherichia coli. and other gram-negative bacilli appear to account for 40% to 60% of all pneumonias.
Gram-negalive bacilli have a propensity lor colonizing the posterior pharynx in debilitated and seriously ill patients. Throat cultures show thai the colonizalion rate correlates directly wilh the severity of associated disease and the degree of functional impairment. Therefore, the high incidence of gram-negative bacillary pneumonia in institutions occurs simply because severely ill or impaired persons are more likely to he found there. Nevertheless, the epidemiology of organisms within a particular institution dictates patterns of colonization and antibiotic sensitivity.
Anaerobic bacteria: Anaerobes appear to play an important role in both community-acquired and nosocomial pneumonia in the elderly. Elderly patients have a tendency to aspirate because they often use sedativesand have associated conditions (such as neurologic disorders) and other illnesses thai alter consciousness. Anaerobes arc estimated to account for up to 20% of community-acquired pneumonia; these common oropharyngeal commensal organisms probably play a role in almost all aspiration pneumonias. The more common anaerobes include Fusobacterium nucleatum, Bactewides melaninosenicus, pepto-streptococci. peptocoeci. and occasionally B.jragilis.
Obtaining a specimen for anaerobic culture and ctiologic identification is difficult. Expectorated sputum becomes contaminated by the normal flora of the upper airways. Specimens obtained by transtracheal aspiration yield a high number of anaerobes.
Legionella Species: Older persons are more susceptible to legionellae. A review of 182 cases in the 1976 Philadelphia outbreak indicated thai 75% of patients infected withL. pneumophila were > 40yrold; the risk of infection among those > 60 yr was about twice that for younger persons. Subsequent studies continue to show a direct correlalion between attack rate and patient age.
Of the pneumonias caused by the 23 recognized Legionella spp, L. pneumophila accounts for about 85%. and L. micdadei accounts for most of the remaining 15%;. Although the pulmonary infection referred to as legionnaires’ disease occurs sporadically, epidemics can occur and usually are associated wilh hotels or hospitals. The diagnosis can be missed unless special tests—using respiratory secretions for direct fluorescent antibody stain and culture on special media and examining urine for L. pneumophila antigen—arc used to make the diagnosis.
Viruses: Viral causes of pneumonia in elderly patients include influenza and parainfluenza viruses, respiratory syncytial virus, and possibly adenoviruses. The most important viral agent of pulmonary infections in adults, especially in the elderly, is influenza (see Ch. 47). Attack rates are age-related, with the incidence in persons > 70 yr about four times that in those < 40 yr. The increased morbidity and mortality rates in the elderly arc far more impressive: persons > 65 yr account for about 90% of influenza-associated deaths in the USA. Epidemics,sometimes with high mortality rates, arc especially problematic in chronic-care facilities: thus, annual influenza vaccination is recommended for staff and residents (see Ch. X5).
Influenza A virus is the most common cause of severe and even fatal illness, in part because of its propensity for antigenic shift. Influenza B, usually relatively benign in younger persons, also may be associated with serious infection and high mortality rales in Ihe elderly. While parainfluenza viruses and respiratory syncytial virus are important pulmonary pathogens in children, they infrequently invade healthy adults; however, the relative frequency of their occurrence in the el-ilerly presumably reflects waning immunity.
Pathogenesis
Microorganisms reach the tracheobronchial tree via four routes: (I) inhalation, (2) aspiration, (3) direct inoculation from contiguous sites, and (4) hematogenous spread. Inhalation and aspiration are much more frequently involved than the other two routes. Pneumonitis occurs when the normal defense mechanisms of the lungs arc overwhelmed or impaired.
Two major factors predisposing to pneumonia are oropharyngeal colonization and silent aspiration. Colonization of the oropharynx wilh various gram-negative bacilli occurs often, especially in patienls whose underlying illness requires treatment in an intensive care unit. Predisposing factors include poor oral hygiene; abnormal swallowing; increased adherence of gram-negative bacilli to mucosal cells; debility from cardiac, respiratory, or neoplastic diseases; reduced ambulation; and frequent exposure to broad-spectrum antibiolics. Silent aspiration of oropharyngeal secretions, Ihe most common mechanism of pulmonary infection, is often related to alcoholism, use of sedatives or narcotics, cerebrovascular disease, esophageal disorders, and nasogastric intubation.
Inhalation pneumonia: Aerosolized organisms inhaled into the lower airways as microparliclcs include Mycobacterium tuberculosis. Legionella spp, and the influenza virus. M. tuberculosis and the influenza virus are transmitted via aerosolized secretions produced by coughing. Although most cases of pneumococcal pneumonia arc acquired by aspiration, inhalation of the organism can also occur, especially in the occasional epidemic. Legionella organisms are nol passed from person to person but arc usually aerosolized from a waterborne source (eg. air conditioners or shower heads). Other waterborne organisms may be introduced into Ihc lower airways by instrumentation or delivered by small-particle aerosols from reservoir nebulizers used with ventilation equipment. Bacteria thai survive well in water include P. aeruginosa. other pseudomonas, Serratia marcescens, Achromobacter, Flavobac-terium, and Acineiobacter spp.Aspiration pneumonia: Pneumonia-causing pathogens in Ihe elderly are often aspirated, but the organisms involved vary in different circumstances. In community-acquired aspiration pneumonia, the usual pathogens are the anaerobic bacteria that normally reside in the gingival crevices (eg, peptostreptococci. fusobacteria, and black-pigmented anaerobes formerly referred to as B. meianinogenicus). In institutionally acquired aspiration pneumonia, the usual pathogens are gram-negative bacilli, sometimes in association with anaerobes. Most cases of pneumococcal and gram-negative bacillary pneumonia presumably follow microaspiration, an occult event resulting in a fairly small inoculum of more virulent bacteria from the posterior pharynx. Large-volume aspiration results in a relatively large inoculum of oropharyngeal bacteria into the lower airways and is associated with conditions that compromise consciousness or cause dysphagia.
Changes with aging (sec also Ch. 45): Many factors contribute to the increased’incidence of pneumonia in elderly palients and to the resultant high morbidity and mortality. Changes in pulmonary function thai occur with aging include decreased cough effectiveness, increased residual volume, decreased compliance, increased closing volume, decreased diffusing capacity, and reduced oxygen saturation. Although these changes do not constitute a substantial risk for pneumonia, they markedly increase susceptibility to complications. This is also true for both chronic obstructive pulmonary disease and chronic bronchitis, which are especially common in older persons. Other conditions that appear to be associated with increased risk for pneumonia as well as increased morbidity in the elderly patient include severe hypoxia, pulmonary edema, acidosis, alcohol intoxication, and azotemia.
Host defenses (see also Chs. 45 and 84): Invasion by microorganisms involves a complex interplay of the mucociliary elevator, alveolar macrophages, polymorphonuclear leukocytes, humoral defenses, and cell-mediated immunity. For most of these defense mechanisms, functional capacity remains intact or is only mildly reduced. The most clearly defined and pronounced deficiency correlated with aging concerns T-cell function (ie. cell-mediated immunity). This defect, readily demonstrated by an increased rate of anergy using common skin test antigens, may contribute to the increased incidence of tuberculosis (see TUBERCULOSIS, below). Other opportunistic palhogens reflecting defective cell-mediated immunity are relalively uncommon unless modifying factors are superimposed, such as administration of corticosteroids, cancer chemotherapy, or lymphoma. A possible exception is Pneumocystis carinii pneumonia, which has been described in a few otherwise healthy elderly patients.
Humoral defenses as measured by serum antibody response to tetanus or pneumococcal vaccine show a somewhat blunted response that is nevertheless generally sufficient to provide protective levels. The response to influenza vaccine is clearly suboptimal in terms of both antibody tilers and clinical protection conferred. The loss of protection afforded by anligens confronted during childhood presumably accounts for the enhanced susceptibility of the elderly lo parainfluenza viruses, respiratory syncytial virus, and possibly the influenza viruses.
Symptoms, Signs, and Diagnosis
The typical clinical features of pneumonia arc cough, fever, and sputum production. They tend to be deceptively subtle in elderly patients, even in cases with an ominous prognosis. The fever pattern may be particularly misleading. Elderly patients have a lower basal temperature and a reduced ability to mount a significant fever in response to infection. To emphasize this point. Dr. Louis Weinstcin often slates, “The older, the colder.” The cough associated with pneumonia is frequently mistaken for chronic lung disease or an upper respiratory infection with bronchitis. The expected findings on physical examination are rales and signs of consolidation over the involved area.
The symptoms and signs, combined with a pulmonary infiltrate on chest x-ray (see Laboratory Findings, below), are diagnostic of pneumonia. The greatest diagnostic challenge is not establishing the presence of pneumonia but sorting out the causative agent. Identifying the causative organism guides (he selection of antimicrobial drugs. The major clinical clues lo the cause of the infection arc the tempo of the disease process, changes on chest x-ray, and the epidemiologic setting.
The onset of pneumococcal pneumonia in the elderly is rarely marked by the typical shaking chill, although it is an acute pulmonary infection. Few clinical features distinguish pneumococcal pneumonia from gram-negative bacillary pneumonia except that the latter is more often acquired in institutions and has a higher mortality rate. Legionnaires’ disease also lends lo bean acute infection, hut ihc initial feature is often fever without prominenl pulmonary symptoms.
When pulmonary infection occurs during an influenza epidemic in any setting, ihe influenza virus should be considered the cause, regardless of the host’s immunization status. Distinguishing primary influenza pneumonia from influenza associated with a superimposed bacterial infection may be virtually impossible. However, primary influenza pneumonia typically has a relentless and hectic progression, and influenza with a superimposed bacterial infection is often an acute febrile illness followed by clinical improvement and subsequent deterioralion with a new infiltrate on chest x-ray.
A different array of pathogens, primarily M. tuberculosis, fungi, and anaerobic bacteria, is more likely involved in chronic pneumonia. These infections arc associaled with fever and symptoms of chronic disease, such as weight loss and anemia.
Anaerobic pulmonary infections tend to involve lung segments that are dependent when the patienl is recumbent, primarily the superior segments of the lower lobes or Ihe posterior segments of the upper lobes. The long-term sequelae are suppurative complications such as lung abscess and empyema. The patient often has putrid sputum or breath, which is suggestive of anaerobic infection.
Another recognized form of what is probably anaerobic pneumonitis is a condition previously referred lo as hypostatic pneumonia or nursing home pneumonia. It is characterized by subtle clinical findings and evidence of pulmonary infiltrates in the lower lobes on chesl x-ray. This condition has not been sufficiently studied bacleriologically. but the suspected pathogens are anaerobic bacteria, S, pneumoniae, H. influenzae, and gram-negative bacilli.
Differential diagnosis: Other conditions with similar findings include atelectasis, heart failure, and pulmonary embolism, wiih or without infarction.
Laboratory Findings
The most useful tests in evaluating suspected pneumonia are the CBC count, the chest x-ray, and microbiologic sludies of respiratory secrelions.
Complete blood count: A leukocyte count is seldom useful unless it is very high (>25,000,yL), suggesting overwhelming pneumonia, or very low (< 3,0QGVL). suggesting a viral infection or overwhelming bacterial pneumonia. A low hemoglobin value suggests a chronic disease, which may be a component of the current condition, such as tuberculosis or anaerobic pulmonary infection, or another underlying condition. Blood cultures should be performed whether or not the patient is febrile.
Chest x-ray: The diagnosis of pneumonia requires Ihsit an infiltrate be evident on chest x-ray. Although the x-ray may be normal early in the disease course, an infiltrate is almost invariably present 24 h after the onset of symptoms. Cough, fever, and sputum production with a normal chest x-ray usually indicate bronchitis or a noninfectious problem. Thus the x-ray becomes pivotal in management decisions, since pneumonia is virtually always treatable with specific antimicrobial agents. Chest x-rays showing cavity formation raise the probability of specific causes, primarily tuberculosis or anaerobic bacterial infection. Patients with pleural effusions on chesl x-ray should have a thoracentesis, which is often helpful in microbiologic diagnosis and is essential for detecting and managing empyema.
Respiratory secretions: Expectorated sputum is unreliable when cultured: even when a potential pathogen is recovered, it may not be responsible for the pulmonary infection. Exceptions to this are M. tuberculosis, pathogenic fungi (Histoplestna, Blastomyces, and Coc-Cidioides), and Legionella spp; the special techniques required for detection virtually always identify them as causative agents. An expectorated sputum culture will usually detect gram-negative bacilli and S. aureus; however, expectorated sputum also has a high rate of false-negative results for S. pneumoniae and H. influenzae and of false-positive results for gram-negative bacilli and S. aureus (although negative results eliminate gram-negative bacilli and S. aureus as causes). Gram stain of expectorated specimens may actually provide more useful information than culture, especially for making therapeutic decisions.
Alternatively, more reliable procedures for recovering conventional bacteria and anaerobes include transtracheal aspiration (a cannula is passed lo the lower airways after percutaneous puncture through the cricothyroid membrane), transthoracic aspiration, and fiberoptic bronchoscopy using the protected brush, but these procedures are rarely used for routine diagnostic evaluation.
Specific recommendations for microbiologic studies include the following techniques. (I) Conventional bacteria: One expectorated sputum sample should be obtained for Gram stain and culture before antibiolic treatment. (2) Legionella spp: Two expectorated sputum samples (or other respiratory secretions) should be obtained for direct fluorescent antibody stain and culture using special media, preferably before erythromycin therapy or after no more than 3 days of such therapy. Urine evaluation for L. pneumophila antigen appears to be Ihe most sensitive test. (3) Anaerobic bacteria: An uncontaminated specimen should be obtained before antibiotic therapy by transtracheal aspiration, transthoracic needle aspiration, thoracentesis, or fiberoptic bronchoscopy using the protected brush. Gram stain of expectorated sputum is of limited value, and culture in anaerobic conditions is not recommended. (4) M. tuberculosis; Three expectorated sputum samples are needed for acid-fast bacillus stain and culture on special media. (5) Influenza virus: Viral culture specimens may be obtained from throat washings, and serologic tests can be done using paired serum specimens collected 3 wk apart. Influenza is usually a presumed diagnosis based on typical symptoms that occur during an epidemic.
Prophylaxis
Preventive measures include Ihe use of vaccines,.judicious use of antibiotics, and intervention during epidemics. Influenza vaccine provides protection against infection; even when the vaccine fails, the severity of disease and the frequency of complications are reduced. Pneumococcal vaccine is also advocated for persons > 65 yr old. Serologic studies indicate that elderly patients develop protective antibody titers following immunization with the commercially available 23-valenl pneumococcal vaccine; clinical trials show a 60% rate of protection in immunocompetent adults (sec Ch. 85).
Patients who are prone to aspiration may benefit from the head-down position, and those who repeatedly aspirate food may benefit from a feeding gastrostomy. Unconscious patients, who are susceptible lo aspiration pneumonia, do not appear to benefit from prophylactic antibiotics. These agents seem to predispose such patients to infection with resistant strains and should be restricted to those with clinical evidence of pneumonia.
Epidemics of pneumonia in institutions such as hospitals or nursing homes are most often caused by the influenza virus. Unlike bacterial infections, influenza tends to affect all exposed persons rather than jusl debilitated persons. Acquisition is from an exogenous rather than an endogenous source, and concurrent outbreaks usually occur in the community. Preventive measures include restriction of visitors, afflicted health care workers, and elective admissions and use of respiratory precautions in patients with documented infection. Outbreaks may be reduced or prevented by immunizing patients and staff with influenza vaccine and using amantadine or rimantadine in exposed patients. When amantadine is given prophylactically, the usual dose for persons with normal renal function is 100 mg/day: however, the drug may cause delirium, especially in persons with reduced renal function in whom doses should be reduced (see also Ch. 47).
When Legionella spp are responsible for outbreaks of pneumonia, the walerborne source must be determined. A source is found in about half of Legionella epidemics; the principal sources are cooling towers of air-conditioning systems and the potable water leading (o contaminated shower heads. Once identified, Legionella spp must be eradicated using either heat or high chlorine concentrations. In pneumonia epidemics involving waterborne gram-negative bacilli, the source is usually contaminated respiratory therapy equipment or instruments such as bronchoscopes.
Treatment
The principal therapeutic modalities are antimicrobial agents, respiratory and other forms of supportive care, and drainage of empyemas and large pleural collections. The selection of antimicrobial agents is difficult but important; it is far easier when the causative organism is identified. Recommendations by specific organism arc given in TABLE 46-1.
When no likely causative organism is identified (enigmatic pneumonia), the recommendation is a regimen that includes erythromycin. This antibiotic alone is usually satisfactory in patients who are not seriously ill with community-acquired pulmonary infections. In seriously ill patients, especially (hose with institutionally acquired pneumonia, the antimicrobial spectrum should be extended with a regimen such as erythromycin and a third-generation cephalosporin, with or without an aminoglycoside.
These recommendations are similar to those For younger patients with pneumonia, although the elderly require closer therapeutic monitoring. Potentially nephrotoxic drugs, primarily aminoglycosides, require particular caution, including serum monitoring and frequent measurements of renal function, and should probably be avoided unless an alternative nonnephrotoxic drug cannot be used. Because older persons have reduced cardiac reserve, IV fluids and electrolytes and other forms of osmotic loading must be given cautiously. Hypersensitivity reactions are no more frequent in elderly than in younger patients, although an age-related risk of antibiotic-associated diarrhea or colitis is common with ampicillin, cephalosporins, or clindamycin. Drug interactions may also occur between antibiotics and other therapeutic agents (eg, warfarin sodium) commonly used in the elderly.

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