PNEUMONIA IN THE ELDERLY

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PNEUMONIA

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PNEUMONIA IN THE ELDERLY Charles Feldman, MB, BCh, PhD, FCP(SA)

An all-encompassing definition of aging has yet to be forthcoming, because of the diversity of phenomena associated with this p r o ~ e s s .With ~ the aging process there is a steadily increasing susceptibility to ultimately fatal disease. It is an interesting observation, however, that the diseases to which humans ultimately succumb do not greatly alter their predetermined life span7 Respiratory tract infections are a major cause of disease and death in the elderly and have been recognized as being so for many years. The important effects of age on the symptoms and clinical presentation of pneumonia were accurately described by Sir William Osler many years ago, in his textbook of Initially described as the "Captain of the Men of Death," pneumonia became known, perhaps more philosophically, as the "friend of the aged."@ Pneumonia in the elderly is often noted to be more severe than in younger patients; the aged need to be admitted more often to hospital and have longer hospital stays, more complications, and, most importantly, a higher mortality In many studies, it is not simply chronologic age per se that has been shown to impact negatively on the manifestations of pneumonia in the elderly, but rather the underlying comorbid illness that is frequently present. In most studies of pneumonia, an age of 60 or 65 years has been used as the cut-off to describe elderly patients.

EPIDEMIOLOGY OF PNEUMONIA

Respiratory tract infections and pneumonia in particular are an important cause of disease and death in the elderly in both the first world and in developing countries. In the United States in 1992, the combined cause-of-death category "pneumo-

nia and influenza" ranked sixth among the leading causes of death.14 In that year, persons aged 65 years or older accounted for 89% of these deaths, and between 1979 and 1992 the pneumonia and influenza death rates for persons aged 65 years or older increased 44%, from 145.6 to 209.1 deaths per 100,000.14In the United Kingdom, pneumonia was the fifth leading cause of death in 1993 and the elderly, the young, and those with underlying disease were most likely to experience morbidity and mortality." Pneumonia in the elderly occurs in three major settings-the community; long-term care facilities (LTCF), such as frail care centers, old age homes, and nursing homes; and the hospital. Community-acquired Pneumonia

Because pneumonia is not a notifiable disease, there are relatively few data on the incidence of community-acquired pneumonia in adults and in the elderly in particular, and most data refer to cases that have been hospitalized for this infect i ~ n Extrapolation .~ of data from these studies leads to the conclusion that community-acquired pneumonia causes significant morbidity and mortality in the elderly. Many studies show an increased incidence and associated increased fatality rate in the elderly. In one study evaluating nonhospitalized elderly patients with pneumonia, the incidence of community-acquired pneumonia in persons 65 years or older ranged between 51.1 and 55.6 per 1000 persons per year.61In another study, it was noted that rates of hospitalization for men greater than 65 years were 11.9 per 1000 personyears, compared with 5.85 per 1000 person-years for those 55 to 64 years old.37In that study, men had a higher rate of hospitalization than women,

From the Division of Pulmonology, Department of Medicine, University of Witwatersrand; and Johannesburg Hospital, Johannesburg, South Africa

CLINICS IN CHEST MEDICINE

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VOLUME 20 * NUMBER 3 SEMEMBER 1999

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and risk factors for the men were current smoking, history of chronic obstructive pulmonary disease (COPD), and history of heart attack. Risk factors for women were COPD, hypertension, and diabetes mellitus. Fine and colleagues23wished to identify a low-risk subset of patients with communityacquired pneumonia who could be safely treated at home. By multivariate analysis, they identified five factors that predisposed to a complicated course in patients with pneumonia. They included age greater than 65 years. Age alone may not be the most important factor in the incidence and mortality of pneumonia, and the excess mortality from pneumonia noted in that study increased progressively with the presence of underlying high-risk conditions.

sizes the possible contribution of underlying comorbid conditions to the risk of nosocomial infection. In one multivariate analysis of risk factors for nosocomial pneumonia, tracheal intubation, depressed level of consciousness, aspiration, and recent chest or abdominal surgery, in addition to age greater than 70 years, were found to be im~ 0 r t a n t . In I ~ a multivariate analysis of risk factors for pneumonia that compared cases with nursing home-associated and nosocomial infections, difficulty with oropharyngeal secretions and the presence of a nasogastric tube best predicted the latter

Long-term Care Facility-acquired Pneumonia

Although many studies have investigated prognostic factors in pneumonia, few deal with possible risk factors for this infection in the general population. Those risk factors' include:

Infections, in general, are important causes of increased morbidity and mortality in LTCF, and lower respiratory tract infections, including pneumonia, account for 15% to 50% of these.I5 The incidence of radiographically confirmed LTCF-acquired pneumonia in one chronic care facility ranged between 69 and 115 per 1000 residents? Few studies have reported the risk factors for LTCF-acquired pneumonia in elderly residents. In one study comparing elderly patients with LTCF pneumonia and with community-acquired pneumonia, the former were more likely to have dementia and cerebrovascular disease, and the latter more likely to be smokers and have COPD." The former cases also tend to be older and to have a signhcantly higher mortality rate." In a multivariate analysis of risk factors associated with the development of pneumonia in a LTCF, difficulty with oropharyngealsecretions, deterioratinghealth, and the occurrence of an unusual event (e.g., confusion, agitation, a recent fall) were most important.30 Nosocomial (Hospital-acquired) Pneumonia

Nosocomial pneumonia is the second most frequent cause of hospital-acquired infection, accounting for some 18% of such infe~ti0ns.I~ It is also the nosocomial infection most frequently associated with death,I7having a case fatality rate as high as 5Oy0.~The risk of nosocomial pneumonia increases in the elderly and was reported in one study to reach a peak of more than 100 episodes per 1000 discharges in patients over 70 years of age.29Other investigators have reported an increased rate of nosocomial pneumonia among older patients and some have noted increasing age as an independent risk factor for nosocomial infections, including pne~monia.~ Although age per se is an important risk factor in some studies, others have not noted this to be so, which further empha-

FACTORS PREDISPOSING TO PNEUMONIA

Age greater than 65 years Underlying comorbid illness Enhanced oropharyngeal colonization Macro- or microaspiration Impaired mucociliary transport Defects in host defense mechanisms Poor nutrition Institutionalization Recent hospitalization Endotracheal/nasogastric intubation General worsening of health A recent study noted that age and a reduced forced expiratory volume in 1 second were the most important risk indicators for severe pneum0nia.3~In the elderly, alcoholism (although uncommon), asthma, immunosuppressive therapy, lung disease, heart disease, institutionalization, and age greater than 70 years have been shown to predispose to p n e ~ m o n i aBasal . ~ ~ ganglia strokes have also been noted to predispose to pneumonia in the elderly, possibly because of the association with frequent aspirationP An additional study has shown that large-volume aspiration and low serum albumin (as a marker of malnutrition) were important risk factors for pneumonia in the Although advanced age predisposes to the development of pulmonary infections, the pathogenesis is uncertain and there are relatively few data on the effects of aging on pulmonary host defense mechanisms.18In many circumstances, it is difficult to separate the effects of aging from those produced by underlying disease. The possible impact of coexistent illnesses on risk for, and death from, pneumonia has been debated for a long time, and the relative importance of each remains unknown. Few data exist on specific defects in host defense that are definitely known to predispose to pneumonia or be associated with increased mortality, although a number of investigators have demonstrated a negative impact of aging on selective

PNEUMONIA IN THE ELDERLY

components of the immune response, as described more hlly subsequently.=,

Oropharyngeal Colonization

Colonization of the oropharynx is an important initial step in the pathogenesis of many pneumonias, including those that are community- or hospital-a~quired.~~ The elderly have been shown to have an increased oropharyngeal colonization rate with pathogens such as Staphylococcus aureus, and aerobic gram-negative bacilli (e.g., Klebsiella pneumoniae and Escherichia ~ o l i ) . ' 21, ~ , 22, 75 This may be transient, lasting less than 3 weeks, but it may also underly their increased risk of pneumonia caused by these pathogens. Although the defects in host defenses that may predispose to enhanced colonization are uncertain, in one study, colonization occurred particularly in patients who were unable to ambulate without assistance, who had difficulty performing their activities of daily living, or who had bladder incontinence, chronic cardiac or respiratory disease, or a deteriorating clinical ~tatus.7~

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Lung Function Impairment

As part of aging there is a loss of pulmonary elasticity because of loss of elastic tissue surrounding alveoli and alveolar ducts, an increase in anteroposterior diameter of the chest because of rib and vertebral calcification, and an overall den These crease in respiratory muscle ~trength.'~, changes may lead to a decreased functional residual capacity and air trapping2' Alveolar Macrophage

The alveolar macrophage plays an important protective role in the lower respiratory tract, and is the first cell that microorganisms come into contact with in the alveolus. Although there are few data on the effects of aging alone on macrophage function, many conditions that exist in the elderly, such as metabolic derangements, including hypoxemia and uremia, and various drugs, are known to impair macrophage function.1s Cell-mediated Immunity

Aspiration

Bacterial pneumonia classically follows the clinically inapparent aspiration of microorganisms that have been harbored in the na~opharynx.'~ Some of the factors that predispose to aspiration include esophageal peristaltic dysfunction, ineffective cough reflex, altered levels of consciousness because of central nervous system disease or medication, dysphagia associated with carcinoma or other esophageal disease, and nasogastric or endotracheal tubes that disrupt normal mechanical These same conditions may also cause macro-aspiration and lead to the aspiration syndromes in the elderly, which are beyond the scope of this article.

Mucociliary Transport

Although the upper respiratory tract is frequently colonized with microorganisms, the lower respiratory tract is normally sterile. The mucociliary escalator is the first-line defense mechanism of the lower respiratory tract, helping clear bacteria and other inhaled particles. In the nonsmoking elderly, mucociliary transport is significantly slower than in younger adults, although the mechanism of this is uncertain.@This defect in mucociliary function is further impaired in smokers and in the elderly with chronic bronchitis. Defects in mucociliary function may be associated with impaired clearance of aspirated particles from the lower respiratory tract.

Although very little is known about pulmonary lymphocyte function in the elderly, there are many data on circulating lymphocytes. There is a change in subpopulations of T lymphocytes in the circulation, with increased percentages of immature cells in the elderly. T lymphocytes from elderly patients have an attenuated mitogenic response to antigen and a reduced capacity to produce or respond to cytokines such as interleukin (IL)-2.l8.19, 25 This attenuated function is accentuated in the presence of chronic disease such as protein-calorie malnutrition. In contrast, B lymphocyte function appears to remain entirely intact,I8 although previously it had been said that B-cell function was im~aired.2~ Also as a consequence of impaired helper T-cell function, the elderly have an impaired antibody response to new antigens.'* Humoral Immunity

In general, serum levels of antibodies in the elderly appear to remain normal, and usually above titers that are presumed necessary to protect against infection.18In fact, levels in elderly patients with COPD have been found to be in excess of what is considered to be protective. Some investigators have noted that there is a poor correlation between antibody levels and protection, when using a functional assay, however.'* Inflammatory Response

Central to the successful eradication of bacteria from the lower respiratory tract is the need for an

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effective inflammatory response, which involves both the humoral and cellular systems.18Polymorphonuclear leukocytes and complement play a large role in the generation of inflammation in the lungs in response to bacterial pathogens. Although polymorphonuclear leukocyte numbers remain constant in the elderly, their reserves appear to be diminished.n Experimental studies have suggested that decreased numbers and proliferative responses of precursor cells may underlie these impaired responses.mData from human studies are conflicting but some investigators have demonstrated defects in chemotaxis, phagocytosis, and bactericidal activity of neutrophil~.~~ This may relate more to the presence of underlying disease, and others have noted entirely normal function in so-called "healthy aged." Concentrations of the C3 component of complement have been noted to be elevated in some healthy aged and are of uncertain significance.'*

CLINICAL MANIFESTATIONS OF PNEUMONIA IN THE ELDERLY

Both advanced age and underlying comorbid illnesses may be responsible for the unusual presentation of pneumonia in the elderly. In some elderly patients, the usual symptoms and signs such as cough, crackles, rhonchi, fever, chills, rigors, and chest pain may be absent (so called "silent infection") and may be replaced by confusion, weakness, lethargy, failure to thrive, anorexia, abdominal pain, episodes of falling, incontinence, headache, delirium, and nonspecific deterioration of their general condition.10,19,21,22,28~42~6677.81.63 44~% Older age in one study was associated with a lower symptom score.5l In another study, delirium was a common clinical manifestation of pneumonia in elderly patients, many of whom were found to be malnourished on admission to hospital.68In yet another study, unusual presentations of pneumonia in the elderly occurred in those with advanced age, cognitive impairment, and baseline functional impairment.3l On examination, classical signs of fever and chest consolidation may be absent in the elderly. One physical sign that has been noted to be an important clue to the possible presence of pneumonia in the elderly is tachypnea. A respiratory rate greater than 26 breaths/minute has been noted to be a good indicator of the presence of a lower respiratory tract infection." Even complicatingbacteremia may present without distinct clinical features in the elderly and, in one study of pneumococcal bacteremia, elderly patients generally had lower fever, less clear-cut history of illness, and a delay in The atypical presentation of pneumonia in the aged may delay diagnosis, with concomitant delay in the initiation of antibiotic therapy, the latter being

considered by many to be an important factor, at least in part, in explaining pneumonia's greater mortality rate in the elderly.58 ETIOLOGY OF PNEUMONIA IN THE ELDERLY

Despite even extensive investigations, the diagnosis of a specific bacterial cause of communityacquired pneumonia is made in fewer than 50% of patients. This is particularly so in the elderly, who may not be able to produce adequate sputum specimens for evaluation. In addition, even if sputum samples are available, they may be contaminated by organisms such as gram-negative pathogens that commonly colonize the oropharynx of the elderly. A number of studies have been undertaken investigating the causes of community-acquired pneumonia and, from these data, it appears that the distribution of bacterial pathogens causing pneumonia in the elderly is different from that in younger adults,5*and include:

Streptococcus pneumoniae Haemophilus infuenzae Enteric gram-negative bacilli Staphylococcus aureus Anaerobes Viruses Other less common pathogens Chlamydia pneumoniae Mycoplama pneumoniae Legionella pneumophila S . pneumoniae still appears to be the most common isolate, causing some 50% of infection^,'^,^^ but infections with H. infuenzae,'2 gram-negative bacilli)6 s. aureus, and anaerobes are more common.1o, 12, 19, 22, 58, 76 Infections with viruses are also seen. The frequency of the various organisms noted in the different studies of community-acquired pneumonia varies according to the parameters that are used for diagnosis (blood and/or respiratory tract culture). In one study using both methods, the pneumococci accounted for 42% of infections, H. infuenzae was isolated in 20%, S. aureus in 14%, and enteric gram-negative pathogens in 37% of ~atients.2~ In many studies,'2,48polymicrobial infections have been noted, occurring in 12% of elderly patients in one study.@Most studies have not commonly found infections with M . pneumoniae, C. pneumoniae, or L. pneumophila,l2, 34, 59 although, in one recent study, C. pneumoniae was the cause of 26.4% of infections in the elderly.41 The causes of pneumonia in the elderly living in long-term care facilities tend to overlap between those of community- and hospital-acquired infections.21While infections with the pneumococci probably still predominate, there is a particularly high rate of infection with gram-negative organisms and s. aureus.", 27 Other pathogens encountered include H. infuenzae, viruses, and anaerobes.

PNEUMONIA IN THE ELDERLY

Elderly residents of nursing homes can also develop respiratory infections with organisms not commonly seen in other settings because of altered immunity and the closed environment of the old age home.77Unusual pathogens sometimes encountered with altered immunity include Moraxella catarrhalis, group B streptococci, and enterococci. Severe infections and even epidemics with respiratory viruses (influenza and respiratory syncytial virus), L. pneumophila, and even C. pneumoniae sometimes occur in nursing homes as a consequence of airborne infection.54 Nosocomial pneumonia is particularly difficult to diagnose and it is also very difficult to be certain whether the organism isolated from a respiratory culture is the causative pathogen. Sick patients in hospital become rapidly colonized with pathogens (sometimes multiple) and the relative importance of each isolate is difficult to ascertain. This problem is particularly difficult in intubated patients who may be colonized with organisms that are readily isolated in the absence of pneumonia. This is in contrast to the nonintubated elderly patient, in whom no organism can be retrieved from the respiratory tract because of an ineffective cough Most cases of nosocomial pneumonia in the elderly appear to be caused by enteric gramnegative bacilli, which account for 60% to 80% of ~ases.5~ Infections with Pseudomonas aeruginosa and K . pneumoniae appear to be most common. Other pathogens encountered in some 10% to 25% of cases include S. aureus, pneumococcus, anaerobes, and, occasionally, viruses and L. p n e ~ m o p h i l aOc.~~ casional nosocomial infections in the elderly, caused by enterococcus, M. catarrhalis, and group B streptococci, have also been noted.

DIAGNOSIS OF THE PRESENCE AND CAUSE OF PNEUMONIA

The diagnosis of both the presence and cause of pneumonia in the elderly, whether community-, nursing. home-, or hospital-acquired, is not straightforward. As noted previously, the clinical presentation of pneumonia in the elderly is often very atypical. A chest radiograph is frequently needed to confirm the presence of pneumonia.% The chest radiograph is therefore an important investigation to perform in the elderly patient with suspected pneumonia. It both helps to confirm the presence of pneumonia and demonstrates the extent of the consolidation (as a negative prognostic indicator) as well as the presence of any comorbid illness ( e g , the presence of COPD) or complications such as cavitation or pleural In the elderly, the chest radiograph may be relatively normal even in the presence of pneumonia. This is said to occur in some patients very early in the course of the infection before the consolidation is fully developed. It is also described in neutropenic

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patients,66,nand in patients admitted to the hospital with dehydration, in which case the consolidation only appears on rehydration.19, 83 The absence of classical chest radiographic changes has also been described in patients with underlying diseases such as COPD and bullous lung disease, in whom the consolidation is patchy." In some cases, pneumonia may be difficult to distinguish from underlying disease (e.g., pulmonary fibrosis) and, in other cases, the presence of noninfective diseases presenting as an apparent pneumonia, such as carcinoma or vasculitis, may be uncovered.%The chest radiograph, much like the clinical picture, is a very poor predictor of the likely microbiologic cause of pneumonia. In line with the recommendations of the American Thoracic Society guidelines on communityacquired most clinicians would perform the least number of additional investigations likely to lead to the diagnosis of a cause. Some that are used include: Chest radiograph Sputum Gram stain and culture (or tracheal suction, if intubated) Blood cultures Routine hematology Routine biochemistry Diagnostic thoracentesis (if pleural effusion) Despite questions of its specificity and sensitivity, it is recommended that sputum Gram stain and culture be performed in all patients from whom sputum is available. This may be used to guide therapy, with due recognition of its limitations.5sIt is further recommended that, in order to improve accuracy, the sputum samples should be taken prior to initiation of antibiotic therapy (without delaying the initiation of treatment) and that specimens be graded to ensure that they are of good quality. In the intubated patient, it is recommended that a tracheal suction sample be obtained for culture. As is the case with sputum specimen sampling, the accuracy of this technique is under question. Suggested alternative techniques to improve the accuracy of pneumonia diagnosis or etiology, especially in ventilator-associated pneumonia, include bronchoscopy with protected specimen brush sampling or bronchoalveolar lavage. These are also controversial and are not recommended routinely.58If sputum is not available, some investigators have suggested that transtracheal aspiration or bronchoscopy may be performed to obtain samples.6, 66 Most clinicians would not use invasive techniques routinely and would tend to reserve these procedures for patients not responding to initial empiric therapy or cases in which less common causes of infection (such as tuberculosis) are suspected.58 Blood cultures are recommended routinely for all hospitalized cases because the isolation of an organism from blood is proof of its causative role." Other investigations routinely recommended in-

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the patient with community-acquired infection should be admitted to hospital or could be safely treated at home or in the long-term care facility, the appropriate supportive therapy needed, and, most importantly, the antibiotic choice. There are no absolute criteria on which the decision to admit patients with pneumonia to hospital can be based.59Those with markers of severe disease or a predicted complicated course need to be admitted. Various studies and numerous guidelines have MORTALITY AND PROGNOSTIC been proposed regarding the optimal management FACTORS IN PNEUMONIA of pneumonia. They have recognized that simple The rate of mortality from pneumonia is inclinical features such as confusion, cyanosis, tachcreased in the elderly and reaches 20% in commuypnea (> 30 breaths/minute), tachycardia (> 140 nity-acquired infections.24, 27, 42*44 In one study, combeats/minute), systolic hypotension (< 90 mm munity-acquired pneumonia's 20% mortality rate Hg), and diastolic hypotension (< 60 mm Hg) compared with 40% for nursing home pneumomay be important criteria directing the need for 11ia.2~In a more recent study, the mortalities were hospital 59 Importantly, a recent study 14% and 32%, re~pectively.4~ Bacteremic pneumoattempting to refine criteria for hospitalization reccoccal infections have a higher mortality rate that ognized that, in addition to the presence of feais age-de~endent~~, 79 and reached 38% in patients tures such as comorbid illness, fever greater than 85 years or older in one study.@Severe commu101"C, immunosuppression, and the isolation of nity-acquired pneumonia (requiring intensive care "high-risk organisms" (e.g., gram-negative bacilli), unit admission) in the elderly was found to have age greater than 65 years is an important factor a mortality rate of 40% in one study, the risk of predicting a complicated c0urse.2~Other possible death being higher in those with radiographic indicators of need for hospitalization in the elderly spread of the infiltrate, shock, previous steroid include likely noncompliance with oral antibiotic treatment, immunosuppression, or Acute Physiolregimens, multiple underlying diseases, and ogy and Chronic Health Evaluation (APACHE) I1 multilobar involvement.10It appears as if many score greater than 22 on a d m i ~ s i o n . ~ ~ more elderly are admitted to hospital than A number of studies have investigated prognosyounger adults with 2o tic factors in pneumonia?, 52, 53, It is commonly Supportive measures include attention to hydrarecognized that age greater than 60 to 65 years is tion and nutrition, support of cardiovascular and an important prognostic indicator of poor outcome renal function, and maintenance of adequate oxyin community-acquired pneumonia.2*3, 9, 52, 55, 63 In genation. Hydration is a particularly important a study assessing 2-year prognosis after commuconsideration in the elderly because ongoing losses nity-acquired pneumonia, however, comorbidity of fluid attributable to hyperventilation and sweatwas the best predictor of likelihood of survival and ing with fever may not be adequately counterbalage was only weakly associated with mortality.8In anced by adequate intake because of altered menone study in the elderly, mortality was more likely tal status.58 One study has suggested that in those who were afebrile, hypotensive, hypoxnutritional supplementation may help the elderly emic, or In a study of patients with recover from chest infectionssoand this would corsevere community-acquired and nosocomial pneurelate well with studies showing the presence of monia requiring intensive care unit admission, admalnutrition in the elderly with pneumonia, which vanced age (> 70 years), a simplified acute physiolalso acts as a risk factor for this infection.@ ogy score (SAPS) index greater than 12, septic With respect to antibiotic therapy, numerous shock, requirement of mechanical ventilation, bilatguidelines have been developed by various naeral pulmonary involvement, and P. aeruginosa as a tional bodies, giving specific recommendations for cause were prognostic factors associated with a both community-acquired2,3*59 and nosocomial infatal outcome.1In another study assessing 30-day fections.I1 Important principles of empiric therapy mortality in elderly patients with lower respiratory for community-acquired pneumonia in the elderly tract infection, patients with malignancy and neuare that the organisms that always need to be rologic disease, atypical presentation, or recurrent covered are the pneumococci and H. infIuenzae.58, and current antibiotic use characterized those with 59, 76 These would be adequately covered in most a high risk of death.%Importantly, administration situations by agents such as amoxicillinof antibiotics within 8 hours of hospital arrival was clavulanate and the second-generationcephalospoassociated with improved survival in a study of the elderly with community-acquired p n e u m ~ n i a . ~ ~rins, which may be given as single agent therapy in those who have no serious coexisting illness. They have the added advantage of being available TREATMENT OF PNEUMONIA IN THE in both parenteral and oral forms.2,3, 19, 21, 58, 82 ELDERLY These agents would also be effective against or" " ganisms such as M . catarrhalis. An important conTreatment decisions that need to be made in sideration is the possibility of infection with pathoelderly patients with pneumonia include whether

clude the full blood count, and measurement of urea, electrolytes, serum enzymes, and protein levels. These are performed as markers of the severity of infection, and to assess the presence of underlying comorbid illness or complications rather than to suggest a likely c a ~ s e . 5Patients ~ with a pleural effusion should have diagnostic thoracentesis to exclude em~yema.5~

PNEUMONIA IN THE ELDERLY

gens such as Legionella and Mycoplasma.2,58 One should always be aware of the prevalence of such organisms in the community or outbreaks of infections with these agents and, in these situations, or in patients in whom these organisms are highly suspect, erythromycin or the new macrolides/azalide agents may be added. In cases with serious underlying illness, additional cover may be needed for more resistant gram-negative pathogens, s. aureus, and anaerobes.58With regard to more serious gram-negative infections, suspected infections with P. aeruginosa should be treated with combination therapy, including two antipseudomonal Anaerobic infections should be suspected and treated in those with aspiration risks. The recommended antibiotics for the elderly in the intensive care unit are the same as those for younger patients and are detailed el~ewhere.5~ Antibiotic therapy should always be tailored to the microbiologic results. Empiric therapy for nursing-home and nosocomial pneumonia is usually broad spectrum, particularly in those undergoing mechanical ventilation. Choice of antibiotics should be based on a knowledge of likely pathogens (”ward epidemiology”) and their sensitivity patterns (“microbial ecology”). The second- and third-generation cephalosporins will cover many nonpseudomonal gramnegative pathogens and H. infuenzae; amoxicillinclavulanate will cover these agents in addition to S. aureus and anaer0bes.5~ P. aeruginosa will usually be covered by agents such as the third-generation cephalosporin, ceftazidime; the fourth-generation cephalosporins; and piperacillin-tazobactam comb i n a t i ~ n The . ~ ~ latter would also have activity against S. aureus and anaerobes.57More severe infections with resistant hospital gram-negative organisms such as P. aeruginosa, K. pneumoniae, and Acinetobacter anitratus may require treatment with agents such as the fluoroquinolones or the carba~enems.5~ An approach to treatment would be to cover ”core organisms,” including gram-negative pathogens, anaerobes, and staphylococci, in nursinghome or. hospitalized patients whereas Pseudomonas should be covered in those with particular risk factors such as mechanical ventilation or corticosteroid ~ s e . 5Treatment ~ for suspected nonpseudomonal infection therefore could be undertaken with ampicillin/sulbactam, second- or thirdgeneration cephalosporins, or piperacillinta~obactam.~~, 82 If Pseudomonas is suspected, then at least one agent active against this organism should be introduced and those with suspected bacteremic infections should receive combination therapy with two antipseudomonal agents.57Severely ill patients, particularly those who have been undergoing mechanical ventilation for more than 5 days and those with particular risk factors for infection with resistant gram-negative organisms, may need empiric therapy with agents such as piperacillin-tazobactam, the fluoroquinolones, or the carbapenems. In any of the situations, one

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should also consider the need for erythromycin to cover Legionella infection.57 PREVENTION OF PNEUMONIA Community-acquired Pneumonia

The general principles for the prevention of pneumonia in the elderly in the community include: Attention to nutrition Pneumococcal vaccine Influenza vaccine Chemoprophylaxis in cases not yet immunized An important consideration for the elderly living in the community is the prevention of pneumonia via the pneumococcal and influenza vaccine^.'^,^ Each of these vaccines has been found to be very effective when used in young, otherwise healthy adults, but to be less effective in the elderly, particularly in high-risk individuals with comorbid diseases. Nevertheless, because these vaccines are relatively safe32and have the potential to prevent serious disease, their routine use in the elderly is recommended.

Pneumococcal Vaccine The currently available 23-valent polysaccharide pneumococcal vaccine contains antigens from serotypes associated with approximately 80% of infections in the aged.5 There is still controversial debate regarding the efficacy of the vaccine in the elderly or in those with comorbid illness. A recent study suggested that vaccination with the 23-valent polysaccharide vaccine did not prevent pneumonia overall, or pneumococcal pneumonia, in middle-aged or elderly individuals.60There has been much further debate about this study, however, which had a rather high median age of patients who were less likely to respond effectively to the vaccine. This study also did not conclusively demonstrate a lack of protection against invasive disease. In addition, a series of epidemiological studies do suggest that the vaccine is 60% to 70% effective overall in protecting elderly patients and that it may have a particularly protective role against invasive d i ~ e a s e . ~

Influenza Vaccine Infections with Influenza in the elderly are associated with high attack rates for pneumonia and significant morbidity and mortality.% Circulating influenza virus strains undergo continuous antigenic change, the so-called ”antigenic drift.” This change in circulating strains of influenza are such that vaccination with the appropriately modified influenza vaccines are recommended on a yearly basis.19,38 The current vaccines have very low levels of local or systemic complications and are well

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tolerated. Although highly effective in young adults, being protective against both influenza A and B, they are less efficacious in older persons. Vaccine efficacy can nevertheless be expected to be 38 Recommendagreater than 60% to 70% tions are that individuals over 65 years be vaccinated on a yearly basis. Use of the influenza vaccine has been shown to be associated with reduction in hospitalization, complications, and death from influenza. It also saves Other

In those who have not been vaccinated, amantadine and rimantadine have been used as chemoprophylaxis against influenza A infection^.'^, 38 Recommendations are that during influenza A epidemics, unprotected patients at high risk receive vaccine and get treated with amantadine or rimantadine for 2 weeks, while awaiting the development of protective antibody levels. These agents are not to be used as substitutes for vaccination. Nosocomial Pneumonia

To avoid infection in long-term care facilities and hospitals, the following should be followed: Hand washing by staff Routine infection-control practices Isolation of patients with multiply resistant respiratory tract pathogens Nutritional support and consideration of techniques of feeding Barrier preparations for stress ulcer prophylaxis Elevation of the head of the bed Subglottic secretion drainage Care in handling ventilator equipment and tubing Lateral rotational bed therapy Selective digestive decontamination As just listed, a number of techniques, both mechanical and pharmacologic, and ranging from simple routine and regular hand washing by staff to more complex procedures such as selective digestive decontamination have been recommended for the prevention of nosocomial pneumonia, and are detailed in the American Thoracic Society consensus statement on nosocomial pneumonia." Even use of the pneumococcal and influenza vaccines may indirectly decrease the risk of nosocomial infection by decreasing the incidence of community-acquired pneumonia and therefore the need for hospital admission. Although good nutrition may be of benefit in the prevention and even therapy of community-acquired infections, its role in prevention of nosocomial pneumonia is less clear-cut. Various aspects of feeding in the intensive care setting may influence the occurrence of nosocomial infections, particularly pneumonia, however, and form the basis of a number of stud-

ies investigating means of decreasing nosocomial infections.l1 Selective Digestive Decontamination

Selective digestive decontamination is a technique that has been developed for the prophylaxis of nosocomial pneumonia, particularly for use in critically ill patients in the intensive care unit settingn This regimen was developed following the recognition that colonization of the oropharynx and upper gastrointestinal tract with gram-negative pathogens is an important first step in the pathogenesis of nosocomial pneumonia. A number of regimens have been tested, but the classical procedure is to apply a paste of antimicrobial agents, usually tobramycin, polymyxin E, and amphotericin B, to the mouth and to introduce these agents via nasogastric tube into the stomach, together with the administration of an initial dose of parenteral cefotaxime. This regimen has been shown to decrease colonization of the oropharynx and stomach by gram-negative pathogens significantly and, in many of the studies there, a significant lowering of the rate of nosocomial pneumonia has also been Concerns have been the inability to lower the mortality rate in those in the intensive care unit despite a lower rate of nosocomial pneumonia and the possibility of the proliferation of resistant microorganisms. The technique is somewhat costly and is labor intensive. Although not used routinely, it may be used increasingly in the future, particularly in specific circumstances.% SUMMARY

Pneumonia, including community-acquired, long-term care facility-associated, and nosocomial infections, is a major cause of morbidity and mortality in the elderly. The aged with pneumonia often present with atypical features, including confusion, lethargy, and general deterioration of condition (so-called "silent infection"). Further investigations, such as a chest radiograph, are more frequently required for diagnosis, but even these results may be normal early in the course of infection, particularly in dehydrated patients. The elderly are more frequently hospitalized for pneumonia and have a greater need for intravenous therapy, longer hospital stay, more prolonged course, greater morbidity, and, ultimately, a poorer outcome. Yet in many studies it is not chronological age per se that impacts negatively on the manifestations of pneumonia in the elderly but rather the presence of comorbid illness. Antibiotic therapy remains the mainstay of therapy for pneumonia, and both community and hospital-based studies confirm the important positive impact of early appropriate empiric antibiotic therapy on outcome. Attention to nutrition and hydration, the use of pneumococcal and influenza vaccination, and a

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Address reprint requests to Charles Feldman, MB, BCh, PhD, FCP(SA) Division of Pulmonology, Department of Medicine University of Witwatersrand, Medical School 7 York Road Parktown, 2193 Johannesburg, South Africa e-mail: [email protected]