Predisposition to Infection in the Elderly

With normal aging, there are mild-to-moderate changes within the immune system. In the elderly, however, it is commonly observed that a more profound deficit occurs with regard to immune function.¹ Not only do these changes render a senior susceptible to certain infections (TABLE 1), but they also affect the clinical presentation of these infections. Atypical presentation of infection in the elderly may be so subtle that pneumonia or a urinary tract infection may manifest with a change in mental status or mild malaise as the only clinical indication of infection.¹ Furthermore, among the contributors to predisposition to infection in the elderly, including comorbid diseases, malnutrition, medications, stress, and infections (TABLE 2), there are reversible causes of acquired immunodeficiency that should be considered, including those that are drug-induced (TABLE 3).¹

Increased Risk for Infection

The immune system is a fundamental organ necessary for the maintenance of life. Immune senescence, a dysregulation of immune responses at multiple levels, and the acquired immune deficiency of aging, therefore, compromise aging adults with respect to infections and cancer; age is the single greatest risk for cancer.² The elderly are more susceptible to infection, which is attributed to a less capable immune response to infectious challenges. Tummala et al illustrate additional susceptibility factors, more common among the elderly, by explaining: a reduced cough reflex can predispose to aspiration pneumonia; urinary or fecal incontinence can predispose to urinary tract and perineal dermatologic infections; and immobility can predispose to pressure ulcers.¹ The authors further indicate that seniors are more susceptible to infections of the skin, gastroenteritis (e.g., from Clostridium difficile), tuberculosis, and shingles (herpes zoster).¹ Infection in the elderly is associated with greater morbidity and mortality, particularly pneumococcal pneumonia, influenza virus infections, and urinary tract infections secondary to a variety of pathogens.^3,4 Further, hospital- and nursing home-acquired infections are increased in older adults (TABLE 1).

Multiple determinants, such as diseases, conditions, or exposures, affect the risk of infection in older adults by contributing to declining immune function.⁵ Depending on the individual, the contribution of host versus social factors varies. Host factors include 1) comorbidities (e.g., diabetes, lung disease, renal failure, peripheral vascular disease); 2) medication use; 3) frailty/impaired cognition (e.g., physical changes such as dry mucous membranes and reduced gag reflex); and 4) immune senescence.⁶ Social factors include 1) poor nutrition; 2) crowding or residing in a long-term care facility; and 3) poor understanding/acceptance of prevention.⁶ The relationships between these risk factors may be very complex; higher infection risk is the result of the accumulation of multiple risk factors.⁶  

Drug-Induced Acquired Immunodeficiency: It has been suggested that drug-induced acquired immunodeficiency is probably more common than is typically appreciated due to the prevalence of polypharmacy in seniors.¹ Neutropenia and lymphocytopenia can result secondary to a variety of commonly prescribed pharmacologic agents (TABLE 3), which should be considered when formulating a pharmaceutical care plan for seniors. Of note, pharmacologic agents that are a reversible cause of acquired immunodeficiency should be seriously addressed as a potential primary reason for infection risk, atypical presentation of infection, or weak response to typical antimicrobial therapy.¹ 

Protein-Energy Malnutrition: With regard to the elderly, there is strong epidemiologic evidence associating protein-energy malnutrition (PEM) to infection. In patients over the age of 65 years who are admitted to the hospital, PEM is present in 30% to 60% of patients.⁶ Community-acquired pneumonia, formation of pressure ulcers, increased risk of nosocomial infections, and a delay in wound healing have all been associated with PEM.⁶ Furthermore, PEM is linked to extended lengths of hospital stay and increased mortality.⁶ 

Infections and Risk for Dementia

Dementia or underlying cognitive impairment is an important risk factor for delirium, to which acute infections may be a contributor; further, delirium is a risk factor for dementia.^7-9 In patients with dementia, malnutrition is associated with a fourfold increase in infections, even with adequate food intake.¹⁰ Despite adequate food intake, progressive cognitive decline without overt systemic manifestations has been associated with chronic infection of the nervous system, as in HIV and syphilis.⁹ Pharmacists will be encountering more seniors living into old age with successfully treated HIV, and these patients will therefore be at risk for dementia.^9,11

  Some other infections that can lead to dementia include tuberculosis and viral encephalitis such as West Nile virus.⁹ While prion disease can occur at any age, Creutzfeldt-Jakob disease should be considered in elderly patients with rapidly progressive dementia, especially if accompanied by other clinical findings such as parkinsonism, myoclonus, or ataxia.^9,12    

Immunizations and Travel Recommendations

In the face of declining immunity, vaccinations are critically important in maintaining the health of seniors.¹ Not only are vaccines effective in preventing pneumococcal pneumonia, influenza, and tetanus, but they also reduce their illness-associated mortality as well.^13-16  While the majority of healthy seniors achieve adequate titers (i.e., those generally assumed protective), frail, chronically ill seniors may not achieve peak antibody titers that are adequately protective against pneumococcal pneumonia or influenza with a single dose of vaccine; some experts recommend supplemental doses, while newer protein/immuno-conjugate vaccines may improve responses in older adults.^1,17-22
With regard to travel, seniors are among the most widely traveled members of our society.⁶ Recommended or required immunizations for travel may include the following vaccines: cholera, yellow fever, hepatitis A, typhoid, and rabies. The efficacy of some vaccines (e.g., hepatitis B, hepatitis A) in older adults is unknown and may be considerably lower in seniors as compared with younger adults.⁶ Seniors may be more likely than their younger counterparts to experience a serious adverse reaction to a vaccine (e.g., yellow fever vaccine).⁶ Furthermore, side effects secondary to chemoprophylaxis (for example, mefloquine for malaria) may be difficult in older adults, and interactions and comorbidities may preclude safe therapy.⁶ Pharmacists are encouraged to guide patients and their caregivers to the Centers for Disease Control and Prevention Website ( www.cdc.gov/travel) for up-to-date information on vaccine recommendations for travel. 

For patients experiencing travel diarrhea, fluids and electrolytes are first-line therapy; fever, bloody stools, or prolonged diarrhea require antimicrobial therapy (i.e., with a quinolone).⁶ An antimotility agent is only recommended as an adjuvant to antimicrobial therapy.⁶ 

Antimicrobial Selection in Seniors

Bolon and Weber offer four steps for a rational approach to the selection of antimicrobial therapy in older adults²³:  

First: If the pathogen is unknown, estimating the most likely causative pathogen is achieved by 1) reviewing clinical and epidemiologic clues and 2) identifying the most likely site of the infection. 

Second: In order to determine the appropriate breadth of an initial antimicrobial course of therapy, the likelihood of antimicrobial resistance should be estimated, and the severity of the patient’s condition and comorbid diseases should be considered.  

Third: In order to select empiric therapy, pharmacologic data must be integrated. This would encompass the evaluation of an antimicrobial’s pharmacokinetic and pharmacodynamic data and the consideration of the risk of toxicity and interactions. 

Fourth: The clinical course and laboratory data must be monitored so that the antimicrobial regimen can be refined and narrowed. Efforts should be directed at the confirmation of a microbiological diagnosis. 

For further discussion on the unique challenges of selecting optimal empiric antimicrobial therapy for older adults with known or suspected infections, consult Reference 23. 

Conclusion

An immune response to an infectious challenge is less potent in an elderly individual, thus elevating morbidity and mortality in this population. Clinicians should have a heightened concern for a broader spectrum of infecting pathogens in a patient with a recent history of hospitalization or residence in long-term care. Due to vulnerability of seniors to infection, clinicians need to exercise increased sensitivity to detect indications of infection so that empiric antimicrobial therapy can be initiated, even in the presence of subtle signs and symptoms. Pharmacists have an opportunity to address those pharmacologic agents that may be a reversible cause of acquired immunodeficiency and to eliminate a potential primary reason for infection risk, atypical presentation of infection, or weak response to typical antimicrobial therapy. 

REFERENCES

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