PNEUMONIA IN THE ELDERLY

RESPIRATORY INFECTIONS

0025-7125/01 $15.00

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

Respiratory tract infections are a major cause of disease and death in the ~ elderly and have been recognized as being so for many ~ e a r s . 9Although initially described by Oslerszas the ”Captain of the Men of Death,” pneumonia was later described by him, perhaps more philosophically, as the ”friend of the aged.” Many differences have been noted in the clinical presentation, severity, management, complications, and outcome of pneumonia in the elderly.24, With the aging process, there is a steady increased susceptibility to ultimately fatal disease. In many studies, it is not simply chronologic age per se, however, that has been shown to have a negative impact on the manifestations of pneumonia in the elderly, but rather underlying comorbid illness that frequently is The diseases to which humans ultimately succumb do not alter greatly their predetermined life span.g Although an all-encompassing definition of aging is not available, owing to the diversity of phenomena associated with this process: in most of the studies of pneumonia, an age of 60 or 65 years has been used as the cutoff to describe elderly patients. EPIDEMIOLOGY OF PNEUMONIA IN THE ELDERLY

Pneumonia is an important cause of disease and death in the elderly throughout the world. Pneumonia incidence increases with age and was 91.6/ 100,000 for persons younger than age 45 years, 277.2/100,000 for persons age 45 to 64 years, and 1012.3/100,000 for persons age 65 years and older in one study In the United States in 1992, pneumonia and influenza from the United ranked sixth among the leading causes of death.I7 Persons age 65 years and older accounted for 89% of these deaths, and between 1979 and 1992, the pneumonia and influenza death rates for persons age 65 years and older increased 44% from 145.6 to 209.1 deaths per 100,000.17In the United Kingdom, pneumonia was the fifth leading cause of death in 1993, and the elderly, along

From the Department of Medicine, Division of Pulmonology, University of the Witwatersrand; and Johannesburg Hospital, Johannesburg, South Africa MEDICAL CLINICS OF NORTH AMERICA VOLUME 85 * NUMBER 6 * NOVEMBER 2001

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with various other patient groups, were most likely to experience morbidity and mortality.59Pneumonia in the elderly occurs in three major settings: (1) within the community, (2) in long-term care facilities (LTCF), and (3) in the hospital. Community-Acquired Pneumonia

Pneumonia is not a notifiable disease, and relatively few data exist about the incidence of community-acquired pneumonia in adults, particularly in the elderly. Most data refer to patients who have been ho~pitalized.~ Extrapolation of these data leads to the conclusion that community-acquired pneumonia causes significant morbidity and mortality in the elderly. In one study, the incidence of community-acquired pneumonia in persons age 65 years and older was 51.1 to 55.6 per 1000 persons per yeats1.In another study, the rates of hospitalization for men older than age 65 years were 11.9 per 1000 person-years compared with 5.85 per 1000 person-years for patients age 55 to 64 years?' Men had a higher rate of hospitalization than women, and risk factors for 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 et a1,3I investigating patients with pneumonia who could be treated successfully at home, identified several factors that predisposed to a complicated course, including age greater than 65 years. Age per se may not be the most important factor in the higher incidence and mortality of pneumonia, but rather the increased likelihood of underlying high-risk conditions in the elderly. The elderly with community-acquired pneumonia are younger, are less acutely and chronically ill, and have a lower in-hospital mortality rate than elderly with nursing home-acquired pneumonia.68 Long-Term Care Facility-Acquired Pneumonia

Infections are important causes of increased morbidity and mortality in LTCF, and lower respiratory tract infections such as pneumonia account for 15% to 50% of infection^.'^ The incidence of radiographically confirmed LTCF-acquired pneumonia in one LTCF was 69 to 115 per 1000 residents6 Few studies have reported on the risk factors. In one study comparing patients with LTCF pneumonia and CAP, the former were more likely to have dementia and cerebrovascular disease, whereas the latter were more likely to be smokers with COPD.63 Patients with LTCF pneumonia tend to be older and to have a significantly higher mortality rate.63,64 A multivariate analysis of risk factors associated with the development of LTCF-acquired pneumonia noted difficulty with oropharyngeal secretions, deteriorating health, and occurrence of an unusual event (e.g., confusion, agitation, fall) as the most Nosocomial Pneumonia

Nosocomial pneumonia is the second most frequent hospital-acquired infection (18% Pneumonia is the most frequent nosocomial infection to be associated with death, with a case-fatality rate of 50%.7,"The risk of nosocomial pneumonia increases in the elderly and in one study reached a peak of greater than 100 episodes per 1000 discharges in patients older than 70 years of age.39 Some investigators noted increasing age per se as an independent risk factor for

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nosocomial infections, including pneumonia: whereas others have not, emphasizing further the possible contribution of underlying comorbid conditions. In one multivariate analysis of risk factors for nosocomial pneumonia, age greater than 70 years, tracheal intubation, depressed level of consciousness, aspiration, and recent chest or abdominal surgery were found to be irnportant.I6Multivariate analysis of risk factors for pneumonia comparing cases with LTCF-acquired and hospital-acquired pneumonia noted difficulty with oropharyngeal secretions and the presence of a nasogastric tube as the best predictors of nosocomial inf ection.4*

PREDISPOSING FACTORS TO PNEUMONIA

Many studies have investigated prognostic factors in pneumonia, but few deal with possible risk factors in the general p0pulation.9~Factors known to predispose to pneumonia in the elderly are as follows: Age greater than 65 years Underlying comorbid illness, including COPD, diabetes mellitus, congestive cardiac failure, malignancy, and neurologic disorders Enhanced oropharyngeal colonization Macroaspiration or microaspiration Impaired mucociliary transport Defects in host defense mechanisms Poor nutrition Institutionalization Recent hospitalization Endotracheal or nasogastric intubation General worsening of health Smoking Recent surgery In the elderly (>70 years old), alcoholism (although uncommon in this age group), asthma, immunosuppressive therapy, lung disease, heart disease, and institutionalization have been shown to predispose to pneumonia.5oOne study showed that large-volume aspiration and low serum albumin (as a marker of malnutrition) were important risk factors for pneumonia in the elderly.89In another study of elderly residents of a LTCF, swallowing difficulty and lack of influenza vaccination were important modifiable risk factors for pneum0nia.5~ Age and chronic pulmonary disease have been noted to be associated with recurrence of pneumonia in patients who had been treated in the hospital for community-acquired pneumonia.44 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.= It often is difficult to separate the effects of aging from the effects produced by underlying disease, and the relative importance of age versus underlying disorders is unknown. Few data exist about specific defects in host defense that are known definitely to predispose to pneumonia or to be associated with increased mortality, although many investigators have shown a negative impact of aging on selective components of the immune response as described s~bsequently.~~, 38, These effects on their own are likely to be relatively modest.

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Oropharyngeal Colonization

Colonization of the oropharynx is an important initial step in the pathogenesis of most p n e ~ m o n i a sThe . ~ ~elderly have increased oropharyngeal colonization rates with pathogens such as Staphylococcus aureus and aerobic gram-negative bacilli (e.g., Klebsiellu pneumoniue and Escherichiu coli).", 27, 28, 99, lo7 Although this increased colonization may be transient, lasting less than 3 weeks, it may underlie the increased risk in the elderly of pneumonia with these pathogens. The defects in host defenses that may predispose to enhanced gram-negative colonization are uncertain, but one study noted that this was more likely in patients who were unable to ambulate without assistance; who had difficulty performing activities of daily living; or who had bladder incontinence, chronic cardiorespiratory disease, or a deteriorating clinical ~tatus.9~ Aspiration

Bacterial pneumonia classically follows clinically inapparent aspiration of microorganisms that have colonized the n a ~ o p h a r y n xFactors .~~ that predispose to aspiration in the elderly include esophageal peristaltic dysfunction, ineffective cough reflex, altered levels of consciousness resulting from central nervous system disease or medication, dysphagia associated with carcinoma or other esophageal disease, and nasogastric or endotracheal tubes that disrupt normal mechanical 24 Basal ganglia strokes have been noted to predispose to pneumonia, possibly as a result of frequent aspiration." These conditions may cause macroaspiration and lead to the aspiration syndromes in the elderly, which are not discussed further in this article. Conversely, angiotensin-converting enzyme inhibitors have been reported to decrease pneumonia incidence in patients with a history of stroke, and more recently treatment of elderly hypertensive patients with angiotensin-converting enzyme inhibitors has been noted to inhibit aspiration pneumonia.2 Mucociliary Transport

Although the upper respiratory tract may be colonized with microorganisms, the lower respiratory tract is normally sterile. The mucociliary escalator is the first-line mechanical defense mechanism of the lower respiratory tract, helping clear bacteria and other inhaled particles. In a nonsmoking elderly person, mucociliary transport may be significantly slower than in younger adults, although the mechanism is uncertain.%,85 This defect in mucociliary function is impaired further in smokers and in elderly with chronic bronchitis. Impaired mucociliary function may be associated with impaired clearance of aspirated particles from the lower respiratory tract. Nutritional Factors

The role of nutritional factors is being recognized increasingly but is incompletely u n d e r s t ~ o d . The ~ , ~effects ~ , ~ ~ of nutrition on host immunity and responses have been Low serum albumin (as a marker of malnutrition) has been noted to be a risk factor for pneumonia in the elderly,89and at least one study

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has suggested that nutritional supplementation may help the elderly recover from chest infections.ID4 Lung Function Impairment

As part of aging, there is a loss of pulmonary elasticity with loss of elastic tissue surrounding alveoli and alveolar ducts, an increase in the anteroposterior diameter of the chest resulting from rib and vertebral calcification, and a de27 These features may be associated with crease in respiratory muscle strength.z4, an impaired cough reflex. These changes may lead to a decreased functional residual capacity and air trapping.27One study noted that age and a reduced forced expiratory volume in 1 second were the most important risk indicators for severe pneumonia.53 Alveolar Macrophage

The alveolar macrophage plays an important protective role in the lower respiratory tract and is the first cell that a microorganism comes into contact with in the alveolus. There are few data on the effects of aging alone on macrophage function, but many conditions that exist in the elderly, such as metabolic derangements, including hypoxemia and uremia, and various drugs are known to impair macrophage function.z3 Cell-Mediated Immunity

Although there are few data about pulmonary lymphocyte function in the elderly, much more is known about 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 in the elderly have been shown to have an attenuated mitogenic response to antigen and a reduced capacity to produce or respond to cytokines such as interleukin (IL)-ZZ3,24, 32 This attenuated function is accentuated in the presence of chronic disease. A study measuring levels and clearance of proinflammatory cytokines (ILlp, IL-6, and tumor necrosis factor-a), chemokines (macrophage inflammatory protein-1p), and anti-inflammatory cytokines (IL-10, sTNFR-I, and IL-1RA) in adults with Streptococcus pneumoniae infections, to test for age-associated differences, noted prolonged inflammatory activity in elderly aged 68 to 91 years.I3 The authors concluded that these results may reflect a decreased ability to control the infection or dysregulation of production or elimination of cytokines in the elderly and may be implicated in the increased morbidity and mortality of pneumococcal infections that occur with increased age. In general, B-lymphocyte function appears to remain entirely intact,z3although previously it was thought that there was impaired B-cell As a consequence of impaired helper T-cell function, however, the elderly have an impaired antibody response to new antigens.z3 Humoral Immunity

In general, serum levels of antibodies in the elderly appear to remain normal and often are elevated above titers that are presumed to be appropriate

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to protect against infection.= Immunoglobulin levels in elderly patients with COPD have been found to be in excess of what is considered to be protective. There may be poor correlation between antibody levels and protection, however, when tested in a functional assayeZ3

Inflammatory Response

To eradicate bacteria from the lower respiratory tract, there is a need for an effective inflammatory response, which involves the humoral and cellular Polymorphonuclear 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.96Experimental studies have suggested that decreased numbers and proliferative responses of precursor cells may underlie these impaired Data from human studies are conflicting, but some investigators have shown defects in chemotaxis, phagocytosis, and bactericidal activity of neutrophils?zThese defects may relate more to the presence of underlying disease; other investigators have noted entirely normal function in the healthy aged. Complement C3 concentrations have been noted to be elevated in some healthy elderly, which is of uncertain significan~e.~~

CLINICAL MANIFESTATIONS OF PNEUMONIA IN THE ELDERLY

Advanced age and underlying comorbid illness may be responsible for the 97 In some elderly patients, unusual presentation of pneumonia in the the usual symptoms, such as cough, fever, chills, rigors, and chest pain, may be absent (so-called silent infection) and be replaced by nonspecific manifestations, such as confusion, lethargy, failure to thrive, headache, weakness, anorexia, abdominal pain, episodes of falling, incontinence, and general deterioration of condition.* In one study, old age was associated with a significantly lower symptom score.7oIn another study, delirium was a common clinical manifestation of pneumonia in elderly patients, many of whom were found to be malnourished.88 Unusual presentations of pneumonia in the elderly occur in cases with advanced age, cognitive impairment, and baseline functional impairment.43 On examination, classic signs of fever and chest consolidation may be absent in the elderly. An important clinical clue to the possible presence of pneumonia in the elderly is tachypnea, and in one study a respiratory rate greater than 26 breaths/min was noted to be a good indicator of the possible presence of a lower respiratory tract i n f e ~ t i o nComplicating .~~ bacteremia may occur without distinct clinical features in the elderly, and in a study of pneumococcal bacteremia, elderly patients generally had lower fever, less clear-cut history of illness, and delay in diagnosis compared with younger patients.33Atypical presentation of pneumonia in the aged may delay diagnosis and initiation of antibiotic therapy, the latter being considered by many to be an important factor, at least in part, to explain the higher mortality of pneumonia in the elderly.78 *References 12, 24, 27, 28, 37, 58, 61, 78, 86, 101, 105, 107, 109.

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CAUSE OF PNEUMONIA IN THE ELDERLY

Despite extensive investigations, the diagnosis of the bacterial cause of community-acquired pneumonia is made in 50% or less of patients overall; this is particularly so in the elderly, who may not be able to produce adequate sputum specimens for e v a l ~ a t i o nEven . ~ ~ if sputum samples are available, they may be contaminated by colonizing organisms, such as gram-negative pathogens. At least partly for these reasons, some workers have suggested that pneumonia in the elderly is more likely to be of unknown cause.ffiAlthough one study suggested that age 60 years or older was not associated with any discemible difference in microbial cause?l it appears from several other studies of community-acquired pneumonia that the distribution of bacterial pathogens causing pneumonia in the elderly is different from that of younger adults.78,79 Common causes of community-acquired pneumonia in the elderly include the following: S. pneumoniae Haemopkilus influenzae Enteric gram-negative bacilli S. aureus Anaerobes Viruses Chlamydia pneumoniae (less common) Mycoplasma pneumoniae (less common) Legionella pneumopkila (less common) S. pneumoniae is the most common isolate, causing approximately 50% of infections,", 58 but infections with Haemopkilus infl~enzae,'~gram-negative baci1li:l S. aureus, and anaerobes are more common.12,15, 24, 27, 78, 97, loo Infections with viruses also are seen. One study suggested that 2% to 9% of pneumonias causing hospitalization or death in the United States are due to respiratory syncytial virus.41The frequency of the various organisms varies according to the parameters on which the diagnosis is based (blood or respiratory tract culture). In a study using both methods, the pneumococcus accounted for 43% of infections; H. influenzae, 20%; S . aureus, 14%; and enteric gram-negative pathogens, 37%.% In many ~tudies,'~, 34, 65 polymicrobial infections have been noted, occurring in 12% of elderly patients in one study.65Most investigators have not found an important role for infections with M. pneumoniae, C. pneumoniae, or L. pneumopkila in the elderly.15,47,78 In one study, 9.3%of patients with M . pneumoniae pneumonia were 65 years old or older, there were no clinical features that distinguished this form of pneumonia from that caused by other agents, and the mortality was 10w.~Another study noted that the incidence of M. pneumoniae pneumonia requiring hospitalization increased with and a third study documented C. pneumoniae as the cause of 26.4%of infections in the elderly.55 The causes of pneumonia in elderly living in LTCF tend to overlap between those of community-acquired and hospital-acquired infectionsz7,97 and include the following: S. pneumoniae H. influenzae Enteric gram-negative bacilli S. aureus Anaerobes Unusual pathogens: Moraxella catarrkalis, group B streptococci, enterococci

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Occasional airborne outbreaks: viruses (influenza and respiratory syncytial), C. pneumoniae, L. pneumophila Although infections with the pneumococcus probably still predominate, there is Other a higher rate of infection with gram-negative organisms and S. aureus.28,34 pathogens encountered include H. infuenzae and anaerobes. Elderly residents of LTCF can develop respiratory infections with organisms not seen commonly in other settings as a consequence of their altered immunity, together with the closed environment of the LTCF.lol Unusual pathogens sometimes encountered include M. catarrhalis, group B streptococci, and enteroc~cci.~~ Severe infections and epidemics with respiratory viruses (influenza and respiratory syncytial virus), L. pneumophila, and C. pneumoniae sometimes occur in LTCF as a consequence of airborne infection.73, 98 Nosocomial pneumonia is particularly difficult to diagnose in the elderly, and it is difficult to be certain whether the organism isolated is the causative pathogen. Sick patients in the hospital become colonized rapidly with pathogens (sometimes multiple), and the relative importance of each isolate is difficult to ascertain. This is particularly so in intubated patients who may be colonized with organisms that are isolated readily in the absence of pneumonia. In many nonintubated elderly patients, no organism can be retrieved from the respiratory tract because of an ineffective cough reflex.= Causes of nosocomial pneumonia in the elderly include the following: Enteric gram-negative bacilli Pseudomonas aeruginosa K. pneumoniae S. aureus S. pneumoniae Anaerobes M . catarrhalis (less common) Group B streptococci (less common) Enterococci (less common) Viruses (less common) L. pneumophila (less common) Most cases of nosocomial pneumonia in the elderly appear to be due to enteric gram-negative bacilli (60% to 80%).= Infections with P. aeruginosa and K. pneumoniae appear to be the most common. Pathogens encountered in 10% to 25% of cases include S. aureus, the pneumococcus, anaerobes, and occasionally viruses and L. pneumophila.n Occasional nosocomial infections have been noted in the elderly with enterococcus, M. catarrhalis, and pyogenic streptococci. DIAGNOSIS OF THE PRESENCE AND CAUSE OF PNEUMONIA

The diagnosis of the presence and cause of any pneumonia in the elderly is not straightforward. The clinical presentation is often atypical. Recommended routine diagnostic workup for hospitalized elderly patients with pneumonia is as follows: Chest radiograph Sputum Gram stain and culture (or tracheal suction if intubated) Blood cultures Routine hematology

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Routine biochemistry Diagnostic thoracentesis (if pleural effusion) A chest radiograph is needed more frequently to confirm the diagnosis.78The chest radiograph is an important investigation to perform in an elderly patient with suspected pneumonia and helps to confirm the presence of pneumonia as well as to show the extent of the consolidation (as a negative prognostic indicator), the presence of any comorbid illness (e.g., the presence of COPD), and the existence of complications such as cavitation or pleural effusion.78In the elderly, the chest radiograph may be relatively normal even in the presence of pneumonia. A normal chest radiograph occurs in some cases early on in the course of the infection, before the consolidation is fully developed. A normal chest radiograph also is described in neutropenic patients86,95*101 and in patients admitted to the hospital with dehydration, with the consolidation appearing only on rehydrati0n.2~. lO9 Absence of classic chest radiographic changes has been described in patients with underlying disease, such as COPD or bullous lung disease, in whom the consolidation is In some cases, pneumonia may be difficult to distinguish from underlying disease (e.g., pulmonary fibrosis, congestive cardiac failure), and in other cases the presence of noninfective disease processes presenting as an apparent pneumonia, such as carcinoma or vasculitis, may be The chest radiograph, similar to the clinical picture, is a poor predictor of likely cause of pneumonia. In the elderly with pneumonia, cases with three or more affected lobes on the chest radiograph have a poor prognosis.95The elderly more commonly have initial radiographic progression of pulmonary infiltrates than younger patients,3*,lo7 and the radiographic changes tend to resolve more slowly.1o7 In line with the recommendations of the American Thoracic Society, most clinicians perform the least number of additional microbiologic investigations likely to lead to the diagnosis of the cause of community-acquired pneumonia.79 Despite questions of its specificity and sensitivity, it is recommended that a sputum Gram stain and culture be performed in all patients from whom sputum is available. Gram stain and culture may be useful in guiding initial therapy, with due recognition of its limitation^.^^ To improve the accuracy of the sputum investigation, samples should be taken before the initiation of antibiotic therapy (but without delaying the start of treatment), and specimens must be graded to ensure that only those of good quality are tested.38In an intubated patient, it is recommended that a specimen of endotracheal secretions be obtained for culture. The accuracy of this technique is questionable, but the suggested alternative techniques to improve the accuracy of diagnosis of pneumonia or its cause, especially in ventilator-associated pneumonia, such as bronchoscopy with protected specimen brush sampling or bronchoalveolar lavage, also are controversial and are not recommended as routine p r o c e d ~ ~ r eIfs .sputum ~~ is not available, some investigators have suggested that invasive techniques, such as transtracheal aspiration or bronchoscopy, be performed to obtain samples!, 86 Most clinicians would not use these invasive techniques routinely and would reserve these investigations for patients not responding to initial empiric therapy and in cases in which unusual infections, such as tuberculosis, are strongly Use of invasive diagnostic testing is limited by the underlying fitness of the elderly patient. Blood cultures are recommended routinely as part of the investigation of all hospitalized patients with pneumonia because the isolation of any organism from blood is proof of its role as a cause.79 Other investigations routinely recommended include complete blood count and the measurement of urea

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and electrolytes, serum enzymes, and protein levels. These investigations are performed as markers of the severity of infection and to assess the presence of underlying comorbid illness or the presence of complications, rather than to assist with the establishment of likely cause.79Patients with a pleural effusion should have diagnostic thoracentesis to exclude e m ~ y e m aSerologic .~~ testing is not recommended routinely because it is expensive and requires paired specimens for appropriate diagnosis. MORTALITY AND PROGNOSTIC FACTORS IN PNEUMONIA IN THE ELDERLY

The mortality from pneumonia is increased in the elderly and may be 20% in community-acquired infections?",34, 58, 61 In one study, the mortality was 20% for community-acquired pneumonia compared with 40% for LTCF-acquired pneumonia.MIn another study, the mortality was 14% and 32y0.6' Bacteremic pneumococcal infections have a higher mortality, which is age dependent'", '03 and reached 38% in patients 85 years old or older in one study? Severe community-acquired pneumonia (patients requiring intensive care unit [ICU] admission) in the elderly was found to have a mortality of 40% in one study; the risk of death was higher in cases with radiographic spread of the infiltrate, shock, previous corticosteroid treatment, immunosuppression, or APACHE I1 score In patients with severe pneumococcal commugreater than 22 on adrni~sion.~~ nity-acquired pneumonia, multivariate analysis in one study revealed various independent predictors of a poor prognosis, including age greater than 65 ~ears.3~ Many studies have investigated prognostic factors in pneumonia.", 54, 71, 74, 83 It commonly is recognized that age greater than 65 years is an important poor 4, 11, 54, 58, 74, 83 One study prognostic indicator in community-acquired pne~monia.~, assessing 2-year prognosis after community-acquired pneumonia noted that comorbidity was the best predictor of survival, however, and that age was associated only weakly with mortality.1° In another study of the elderly, mortality was higher in patients who were afebrile, hypotensive, hypoxemic, or incontinent.'Oo Among patients with severe community-acquired and nosocomial pneumonia requiring ICU admission, advanced age (270 years), a simplified acute physiology score (SAPS) index greater than 12, septic shock, requirement for mechanical ventilation, bilateral pulmonary involvement, and l? aeruginosa as the causative pathogen were important prognostic factors associated with a fatal outcome.' In a study assessing 30-day mortality in elderly patients with lower respiratory tract infection, patients with malignancy and neurologic disease, atypical presentation, or recurrent or current antibiotic use had a high risk of death.& Administration of antibiotics within 8 hours of hospital arrival was associated with improved survival in a study of elderly with community-acquired pneumonia.69Age and chronic pulmonary disease put elderly patients at risk of recurrence of pneumonia after hospital treatment for community-acquired pneumonia.@One study indicated that elderly patients treated for community-acquired pneumonia are at high risk of subsequent mortality for several ~ e a r s . 4 ~ Fine et alZ9developed a risk classification system based on age, gender, presence of comorbid illness, vital signs, and radiographic and laboratory abnormalities that permits estimation of risk of death. This classification system was investigated and shown to provide valid estimation of length of hospital stay, requirement of ICU admission, and risk of death in the elderlyz5In that study, the British Thoracic Society (BTS) rule most closely reflected risk of death from

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pneumonia when Fine's classification was used as reference.= Others have suggested that the BTS and the modified BTS rules did not perform well in a validation study that included a high proportion (48%) of elderly patients (275 years) compared with the derivation These and other investigators recommended their own staging system or discriminant rules.18,25 TREATMENT OF PNEUMONIA IN THE ELDERLY

Decisions that need to be made in elderly patients with pneumonia include whether the patient with community-acquired infection should be admitted to the hospital or could be treated safely at home or in the LTCF, the appropriate supportive therapy needed, and most importantly the initial antibiotic choice. There are no absolute criteria on which the decision to admit patients with pneumonia to the hospital can be based.79Patients with markers of severe disease and patients with a predicted complicated course need admission. Various studies and numerous guidelines have been put forward on the optimal management of pneumonia and have recognized that simple clinical features, such as confusion, cyanosis, tachypnea (>30 breaths/min), tachycardia (>140 beats/min), systolic hypotension (<90 mm Hg), and diastolic hypotension (<60 mm Hg), may be important criteria directing the need for hospital admission.78,79 A study attempting to refine criteria for hospitalization has recognized that in addition to the presence of comorbid illness, fever greater than 101"C, immunosuppression, and the isolation of high-risk organisms ( e g , gram-negative bacilli), age greater than 65 years is an important factor predicting a complicated course.31 Other possible indicators of need for hospitalization in the elderly include likely noncompliance with oral antibiotic regimens, multiple underlying diseases, and multilobar involvement.12Many more elderly apparently are admitted to the hospital than younger adults with pneumonia.12,26 Supportive measures include adequate hydration and nutrition, support of Io7 Hydracardiovascular and renal function, and maintenance of 0xygenation.9~. tion is a particularly important consideration in the elderly because ongoing losses of fluid resulting from hyperventilation and sweating with fever may not be counterbalanced adequately by intake because of altered mental One study suggested that nutritional supplementation may help elderly patients recover from chest infections,'04 and this would correlate well with other studies documenting the presence of malnutrition in the elderly, which is a risk factor for this infection.88*89 Regarding antibiotic therapy, numerous guidelines have been developed by various national bodies, which give specific recommendations for communityacquired3,4, 79 and nosocomial infection^.'^ Important principles of empiric therapy for community-acquired pneumonia in the elderly are that treatment always should cover infection with S. pneumoniae and H. injlumzae?8~79~100 These pathogens would be covered adequately in most situations with agents such as amoxicillin-clavulanate and the second-generation cephalosporins, which may be given as monotherapy in cases without serious coexisting illness and have the added advantage of being available in parenteral and oral forms.3,4, 12, 24, 27, 78, lo8 Third-generation and fourth-generation cephalosporins have been shown in prospective studies to be effective in the elderly.40All these agents also would be effective against M . catarrhalis. An important consideration is the possibility of infection with pathogens such as Legionella and Mycoplasma.3, 78 Clinicians always should be aware of the prevalence and outbreaks of infection with these organisms. When infection with these organisms is strongly suspected,

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erythromycin or one of the new macrolides/azalide agents should be added. In cases with serious underlying illness, additional cover may be needed for more resistant gram-negative pathogens, for S. aureus, and for anaerobe^.^^ In one study of primarily community-dwelling elderly patients hospitalized with pneumonia, three initial treatment regimens were found to be associated independently with a lower 30-day mortality: (1) a second-generation cephalosporin plus a macrolide, (2) a nonpseudomonal third-generation cephalosporin plus a macrolide, and (3) a fluoroquinolone These data need to be interpreted carefully, however, because although the authors attempted to control for severity of illness using state-of-the-art statistical procedures, it appeared that macrolides were used more commonly in patients with less severe illness.z0 Although the addition of a macrolide to standard therapy for communityacquired pneumonia has been suggested by some for elderly patients, based largely on a study from Israel in which serologic evidence of C. pneumoniae infection occurred in 26% of this has been questioned by others for many reasons, including the need to confirm the role of this pathogen as the causative agent.lo6 Infections with l? aeruginosa and K. pneumoniae preferably should be treated with combination therapy, particularly in sicker patients.79Anaerobic infections should be suspected and treated appropriately in patients with aspiration. The recommended antibiotics for elderly patients in the ICU are the same as that for younger patients and are detailed elsewhere.79Antibiotic therapy always should be tailored subsequently to the microbiologic results. Empiric therapy for LTCF-acquired pneumonia and nosocomial pneumonia usually is broad spectrum, particularly in patients undergoing mechanical ventilation. Choice of antibiotics should be based on knowledge of likely pathogens (ward epidemiology) and their sensitivity patterns (microbial ecology). The secondgeneration and third-generation cephalosporins cover many nonpseudomonal gram-negative pathogens and H. influenzae, whereas amoxicillin-clavulanatecovers these pathogens in addition to S. aureus and anaerobes.n P. aeruginosa usually is covered by agents such as the third-generation cephalosporin ceftazidime, the fourth-generation cephalosporin cefepime, and piperacillin-tazobactam combination.n Piperacillin-tazobactam combination also has activity against S. aureus and anaerobesn More severe infections with resistant hospital gram-negative organisms, such as l? aeruginosa, K. pneumoniae, and Acinetobacter anitratus, may require treatment with additional agents, such as the fluoroquinolones or the carbapenems.n An approach to treatment of patients in LTCF or hospitals would be to cover core organisms, including gram-negative pathogens, anaerobes, and staphylococci, whereas Pseudomonas should be covered in the case of particular risk factors, such as mechanical ventilation and corticosteroid use.77Treatment for suspected nonpseudomonal infection could be undertaken with amoxicillin-clavulanate, second-generation or third-generation cephalosporins, or piperacillin-tazobactam.77,*08 If Pseudomonas is suspected, at least one agent active against this organism should be introduced, and patients with bacteremic infections should receive combination therapy with two antipseudomonal agents.n Severely ill patients, particularly those who have been undergoing mechanical ventilation for more than 5 days, and patients 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. The clinician should consider the need in any of these situations for a macrolide to cover Legionella.n Antibiotic therapy always should be tailored to the microbiologic results.

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PREVENTION OF PNEUMONIA

The general principles for the prevention of pneumonia in the elderly in various settings are shown in the accompanying box.

General Principles for the Prevention of Pneumonia in the Elderly Community-acquiredinfections Attention to nutrition, smoking cessation Pneumococcal vaccine Influenza vaccine Chemoprophylaxis; in cases not yet immunized Long-term care facility/hospital infections Hand washing by staff Routine infection control practices Isolation of patients with multiply-resistant respiratory tract pathogens Nutritional support and specific 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

Community-Acquired Pneumonia An important consideration for the elderly living in the community is the potential benefit of prevention of pneumonia with the use of the pneumococcal and influenza vaccine^?^,^^ Each of these vaccines has been found to be effective when used in young, otherwise healthy adults but to be less effective in the elderly, particularly in high-risk cases with underlying comorbid diseases. Nevertheless, because these vaccines are relatively safe" and have the potential to prevent serious disease, their routine use in the elderly is highly recommended.

Pneumococcal Vaccine

The currently available 23-valent polysaccharide pneumococcal vaccine contains antigens from serotypes associated with greater than or equal to 85% of pneumococcal infections in the aged.7There is debate regarding the efficacy of the vaccine in the elderly and patients with underlying comorbid illness.38A study suggested tkat vaccination did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged or elderly individuals.80This study did not document a lack of efficacy in preventing invasive disease. A series of epidemiologic studies suggests that the vaccine is 60% to 70% effective in protecting elderly patients and that it has a particularly protective role against invasive d i ~ e a s eIn . ~ one study, vaccination of elderly persons with chronic lung disease was associated with fewer hospitalizations for pneumonia, fewer deaths, and direct medical care cost savings."

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Influenza Vaccine

Infections with influenza in the elderly are associated with high attack rates for pneumonia and significant morbidity and mortality?2Circulating influenza strains undergo continuous antigenic change, the so-called antigenic drift. Because of this change in circulating strains of influenza, annual vaccination with the appropriately modified influenza vaccines is recommended on a yearly 52 The current vaccines have low levels of local or systemic complications and are well tolerated. Although highly effective in young adults against influenza A and B, the efficacy of these vaccines is said to be less in older persons. 52 RecomNevertheless, vaccine efficacy is expected to be 60% to 70% mendations are that individuals older than age 65 years be vaccinated on a yearly Vaccine use has been shown to be associated with reduction in hospitalization, complications, and death from influenza and to be cost saving.76 Other Chemoprophylaxis

In patients who have not been vaccinated, amantadine and rimantadine Recomhave been used as chemoprophylaxis against influenza A infection~.2~,~~ mendations are that during influenza A epidemics, unprotected patients at high risk receive vaccine and be treated with amantadine or rimantadine for 2 weeks, while awaiting the development of protective antibody levels. The neuraminidase inhibitors, oseltamivir and zanamivir, may be effective in this setting. These agents should not be used as substitutes for vaccination. More recently, it has been suggested that amantadine may play a role in the prevention of pneumonia in elderly stroke patients, and although this may be due largely to its antiviral effects, it also has been noted that amantadine may improve the conscious state as well as improve lower esophageal sphincter function, and these improvements may contribute to the beneficial effects.93 Nosocomial Pneumonia

Many mechanical and pharmacologic techniques, 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 in different settings and are detailed in the American Thoracic Society Guidelines on nosocomial p n e ~ m o n i aUse . ~ ~of the pneumococcal and influenza vaccines may decrease the risk of nosocomial infection indirectly because by decreasing the incidence of pneumonia in general they decrease overall hospital admission. 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 ICU setting.94This regimen was developed after the recognition that colonization of the oropharynx and upper gastrointestinal tract with gramnegative pathogens is an important first step in the pathogenesis of nosocomial pneumonia. Many regimens have been tested but the classic procedure is the application of a paste of antimicrobial agents, most commonly tobramycin, polymixin E, and amphotericin B to the mouth and by nasogastic tube to the stomach, together with the administration of an initial dose of parenteral

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cefotaxime. This regimen has been shown to decrease significantly colonization of the oropharynx and stomach by gram-negative pathogens, and in many of the studies there has been a significant lowering of the rate of nosocomial pneumonia.52Concerns have been the inability to lower the mortality rate in cases in the ICU despite a lower rate of nosocomial pneumonia and the possibility of proliferation of resistant microorganisms. The technique is costly and is labor intensive. Although not routinely in use, such techniques may be used increasingly, and particularly in specific circumstances, in the SUMMARY

Pneumonia, including community-acquired, LTCF-acquired, and nosocomial infections, is a major cause of morbidity and mortality among the elderly. The aged with pneumonia often present with atypical features, including confusion, lethargy, and general deterioration of condition (silent infection). Further investigations, such as a chest radiograph frequently are required for diagnosis. The chest radiograph may be normal early on in the course of infection, particularly in dehydrated patients. The elderly are hospitalized more frequently for pneumonia, have a greater need for intravenous therapy, have a longer hospital stay, have a more prolonged course, have greater morbidity, and ultimately have a poorer outcome. Nevertheless, it may not be chronologic age per se that has a negative impact on the manifestations and outcome of pneumonia in the elderly, but rather the presence of underlying comorbid illness. The mainstay of therapy for pneumonia is antibiotics, and studies in the community and hospital have confirmed the important positive impact of early appropriate empiric therapy on outcome. Many relatively simple procedures, including attention to nutrition, influenza and pneumococcal vaccination, and avoidance of intubation, may help limit the occurrence of such infections. References 1. Almirall J, Mesalles E, Hamburg J, et a1 Prognostic factors of pneumonia requiring admission to the intensive care unit. Chest 107511, 1995 2. Arai T, Yasuda Y, Toshima S, et al: ACE inhibitors and pneumonia in elderly people. Lancet 352:1937, 1998 3. Bartlett JG, Mundy LM: Community-acquired pneumonia. N Engl J Med 333:1618, 1995 4. Barlett JG, Breiman RF, Mandell LA, et a1 Community-acquired pneumonia in adults: Guidelines for management. Clin Infect Dis 26811, 1998 5. Bell RA, High Kp: Alterations of immune defense mechanisms in the elderly: The role of nutrition. Infect Med 14:415, 1997 6. Bentley D W Pneumococcal vaccine in the institutionalized elderly: Review of past and recent studies. Rev Infect Dis 3(suppl):S61, 1981 7. Bentley DW, Mylotte J M Epidemiology of respiratory infections in the elderly. In Niederman MS (ed): Respiratory Infections in the Elderly. New York, Raven Press, 1991, p 1 8. Berk SL, Holtsclaw SA, Kahn A, et al: Transtracheal aspiration in the severely ill elderly patient with bacterial pneumonia. J Am Geriatr SOC29228, 1981 9. Blumenthal H T Biology of aging. In Steinberg FU (ed): Care of the Geriatric Patient in the Tradition of E. V. Cowdry, ed 6. St Louis, CV Mosby, 1983 Wagener MM, et a1 Is pneumonia really the old man’s friend? 10. Brancati FL, Chow JW, Two-year prognosis after community-acquired pneumonia. Lancet 34230,1993 11. British Thoracic Society and the Public Health Laboratory Service: Community-

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Address reprint requests to Charles Feldman, MB, BCh, PhD, FRCP, FCP(SA) Department of Medicine Division of Pulmonology University of the Witwatersrand Medical School 7 York Road Parktown, 2193 Johannesburg, South Africa e-mail 014 [email protected]