Infections in Older Adults: The Art of Early Recognition

Compared with younger adults, older adults are more likely to contract certain infections and have higher morbidity and mortality.¹ Specifically, pneumonia and influenza are among the most common mortality causes.² Infections of the urinary tract, lower respiratory tract, and skin and soft tissue, as well as intra-abdominal infections appear to have a higher incidence in older adults. The mortality rates of most of these infections are at least three times higher in older patients than in younger adult patients with the same disease.³

In the long-term care setting, the majority of people who live in long-term care facilities (LTCFs) are frail or pre-frail, and older. More than 4 million Americans are admitted to or reside in nursing homes (NHs) and skilled nursing facilities each year, and nearly 1 million people reside in assisted living facilities.⁴ Data on infections in LTCFs are limited, but it has been estimated that 1 to 3 million serious infections occur every year in these facilities.⁵ Infections are a major cause of hospitalization and mortality, with as many as 380,000 LTCF residents dying of infections every year.⁵ The reported incidence of infections in such facilities varies depending on the type of institution and the frailty of its residents, but it is estimated to be 10 to 20 infections per 100 residents per month. Coupled with comorbidities and declining functional status, frailty leads to increased morbidity and mortality, including from infection. It also blunts the early infection signs, leading to delays in treatment.⁶ Nearly 75% to 80% of infections in this setting are caused by urinary tract infections (UTIs), lower respiratory tract infections, and skin and soft tissue infections, which include infected pressure wounds.⁶

Older adults in general, whether they reside in the community or LTCFs, are highly vulnerable to infections because of their frailty, physical disabilities, and altered host resistance. This article summarizes the factors contributing to increased risk of infection in older adults, attempts to characterize challenges we can monitor when diagnosing infections, and reviews common infections and scoring systems that can be applied to assist with clinical decision-making when diagnosing these infections.

Natural barriers to infection within the skin, lungs, and gastrointestinal tract often lose effectiveness with age, allowing invasion of pathogenic organisms. The aging immune system shows withering of the cellular and humoral immunity, including decreased cell populations, loss of proliferating capacity of immune cells, and decreased production of cytokines. This loss of immune function can lead to high risk of intracellular pathogens.⁷ Decreased antibody response to vaccines, related to low toll-like receptors, senescence of CD8 T cells, reduced CD4+ naïve, and changes in B-cell biology can also contribute to a blunted immune response.⁸

Immunosuppression is augmented by concomitant medical problems, such as diabetes mellitus, chronic obstructive pulmonary disease, and heart failure, as well as malnutrition and polypharmacy, which have been noted to render older adult patients more susceptible to common infections and increase the exhibition of poorer vaccine responses.⁹

Blunted physiologic reserves in older adults cause various changes that increase risk of infection, such as decreased cough reflex, impaired arterial and venous circulation, decreased detrusor muscle tonicity, decreased gastric acidity, and prostate enlargement.

Communal residence in NHs and time spent at community social centers contribute to increased risk of infection in older adults. Institutionalization is a major risk factor for acquiring infection and exposure to antibiotic-resistant organisms.¹⁰ Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), fluoroquinolone-resistant Streptococcus pneumoniae, and multidrug resistant gram-negative bacilli tend to be more common in institutions.¹¹ Antibiotic resistance is facilitated by frail hosts, proximity of residents, and persistent antibiotic pressure in this context. Indwelling devices, such as urinary catheters, intravenous catheters, feeding tubes, and tracheostomies, are more common in older adults and contribute to an increased susceptibility to infection.

Older adults often present with nonspecific decline from their baseline functional status. Cognitive impairment contributes to the atypical presentation of infections, which further reduces their capacity to communicate symptoms. The classical manifestations of infection, fever, and leukocytosis, may be absent or blunted in 20% to 30% of cases.¹² Fever can be absent in 30% to 50% of frail older adults, even in cases of serious infections, such as pneumonia or endocarditis.¹³ Thermoregulation mechanisms, such as shivering, vasoconstriction, hypothalamic regulation, and thermogenesis by brown adipose tissue, are impaired in older age and can be responsible for these presentations. Women, patients with dementia, patients who are dependent in their activities of daily living, and patients with a BMI less than 20 may be at particularly high risk for this presentation.¹⁴

In a prospective study of patients over 75 years of age in the emergency department setting, it was demonstrated that a tympanal body temperature higher than 37.3°C (99.14°F) and a rectal body temperature higher than 37.8°C (100.04°F) is a reliable marker of a bacterial infection.^14,15 Viral illness presents with fever in less than 5% of cases.¹⁴ The definition of fever in older adults is a temperature of 37.8°C (100°F) and tends to be associated with markers of serious illness more than 75% of the time.¹⁶ But severe infection may occur in the absence of fever. Failure to mount a febrile response to infection has been noted in NH patients.¹⁷ Mean baseline morning rectal temperature was 37°C in 22 patients whose oral temperatures could not be easily determined. The mean oral temperature of 85 other residents was 37.3°C. Diurnal variation was only 0.3°C for rectal temperatures and 0.2°C for oral temperatures. ¹⁴ In another study, 74 afebrile hospitalized geriatric inpatients were similarly studied to determine the normal range of temperatures for the frail older adult.¹⁸ This study established the upward limits for normal temperatures: 37.5°C rectal, 37.3°C oral, 37°C axillary, and 37°C proximal auditory canal.

Fever of unknown origin often occurs in older adults. It is defined as temperature greater than 38.3°C (101°F) for 3 weeks and undiagnosed after 1 week of medical evaluation.¹⁹ The etiology varies and may include abscess, bacterial endocarditis, tuberculosis, perinephric abscess, or osteomyelitis. Giant cell arteritis and polymyalgia rheumatica account for 10% of fever of unknown origin and should be held high in the differential diagnosis, especially in context of an elevated erythrocyte sedimentation rate and abnormal liver function tests.²⁰ Malignancy, especially lymphoma, drug fever, deep vein thrombosis, and hyperthyroidism, should also remain high in the differential diagnosis of a febrile older adult.

Pneumonia in the Older Adult

In the United States, pneumonia and influenza combined rank high and are among the leading causes of death in patients older than 65 years of age.²¹ Morbidity and mortality for pneumonia increases dramatically with age. Half of all cases of pneumonia involve patients over the age of 65 years.²² For NH residents, pneumonia is the second leading cause of infection and the second leading cause of bacteremia. Predisposing factors leading to high prevalence include aging of the respiratory tract and lung tissue, changes in the mucocilliary transport system associated with age and smoking, and changes in lung capacity, elasticity, and compliance. Additionally, etiology can be associated with microaspiration of bacterial pathogens colonizing the oropharynx in the setting of dysphagia.²³ The prevalence of dysphagia in NHs is approximately 50%, and 30% of older adults with dysphagia develop aspiration.²⁴

Some of the classic symptoms of pneumonia in older adults include productive cough, fever, pleurisy, and rigors. However, only 34% of NH patients were noted to have a cough in the setting of pneumonia compared with 60% of community dwellers.²⁵

The most common causative organism in community-acquired pneumonia (CAP) and nursing home–acquired pneumonia (NHAP) patients is S pneumoniae and is isolated from sputum in 20% to 30% of CAP cases in older adults.²⁶Haemophilus influenzae tends to occur in patients who have chronic lung disease, are male, and present with productive cough.²⁷Legionella pneumophila infection is sporadic, mainly occurring in summer or fall and may be found in the water condensed from air conditioning. Mycoplasma pneumoniae is an atypical pathogen less likely to be found in older adults. S aureus occurs with nosocomial infection, and these pneumonias tend to have multilobar infiltration, are often associated with bacteremia, and classically occur after influenza. Gram-negative bacilli are more common in NHs, accounting for 12% of NHAP cases.²⁸ A causative organism is not identified in 60% of older adults with pneumonia.²⁹ A newly discovered agent, human metapneumovirus, should be considered in presence of bronchospasm or if the patient exhibits wheezing.³⁰

NH-acquired pneumonia fits under the umbrella term of healthcare-associated pneumonia and is defined as pneumonia occurring under the following conditions: (1) within 48 hours of admission to an LTCF or NH; (2) if the patient has been treated with intravenous antibiotics, chemotherapy, or wound care in the past 30 days while in an LTCF or NH; (3) if the patient has been hospitalized in an acute care setting for 2 days or more in the preceding 90 days; or (4) if the patient attends hemodialysis sessions. NH–acquired pneumonia is associated with increased comorbidity and poorer functional status. The mortality rate of NHAP is 19% to 53% compared with 8% to 14% of CAP.³¹ With NHAP, gram-negative rods, anaerobes, and S aureus are more common.³¹Pseudomonas rates vary from 4% to 25% but can be as high as 52%.³¹

Aspiration pneumonia is common in the NH population and is often associated with oropharyngeal dysphagia and regurgitation of gastric contents. Inadequate oral care significantly increases the risk for developing pneumonia.³² Dental plaque has been particularly studied as a source of bacteria that may cause respiratory infections. A study in Japan showed an association between periodontal disease and increased mortality from pneumonia.³²

Urinary Tract Infections

UTIs are also very common infections in older adults and should be considered a spectrum of infections from asymptomatic bacteriuria and cystitis to pyelonephritis and urosepsis, with a mortality rate of 20% to 40%.³³ The prevalence in the community is 5% to 30%, but in the NH it rises to 17% to 55% of women and 15% to 31% of men.³¹ Anatomic changes with aging, such as changes in prostatic size, changes in vaginal flora associated with menopause, obstructive uropathy (from pelvic fractures, tumors, gastrointestinal disease, kidney stones, or blood clots), and anatomic changes related to childbirth or reproductive surgery, such as higher rates of incontinence, frequent urologic instrumentation, comorbid diseases, and medications that alter bladder function, all lead to a high incidence of UTIs. The most common pathogens are Escherichia coli, Proteus, Klebsiella, Enterococcus, Pseudomonas, and Staphylococcus. The prevalence of gram-positive organisms has also been increasing.³⁴ A catheter change in the setting of UTI is associated with improved clinical outcomes.

UTIs have dramatically increased since 2000, particularly in those aged 85 years and over.³⁵ The incidence of sepsis and its associated mortality increases disproportionately with age, and UTI in men is more likely to be severe. The diagnosis again can be problematic because these patients are less likely to present with typical urinary symptoms compared to younger patients. Many markers for UTIs have been studied, but the gold standard for diagnosis of a UTI remains a positive urine culture. Delaying or withholding antibiotics in older adults with clinical symptoms of UTI seems to be associated with a higher risk of sepsis and death.³⁶ Recent studies show that bloodstream infections are significantly more common in patients who had delayed administration of antibiotics. Patients not treated immediately were nearly twice as likely to be admitted to hospital compared with patients who were treated quickly.³⁷

Bacteremia

In the same context of vague presentation, bacteremic older adults are more likely to have gram-negative rods isolated, which tend to be from gastrointestinal and genitourinary sources. This trend seems to increase steeply during the eighth and ninth decades of life.³⁸ Mortality of bacteremia increases with age, with gram-negative bacteremia mortality rates of 37% to 50% in older adults.³⁸ Diabetes mellitus doubles the risk of bacteremia. Other risk factors include cardiovascular disease, neuropsychiatric disease, malignancy, stroke, recent invasive procedures, and presence of indwelling catheters.³⁹ As with other infectious states discussed, absence of fever cannot be taken as proof of absence of bacteremia. Normal white blood cell count is present in 20% to 45% of older bacteremic patients.⁴⁰ Independent predictors for bacteremia include change of mental status, vomiting, and white blood cell count band forms greater than 6.40 gram-negative bacteremia is most common and accounts for 70% of patients, followed by gram-positive bacteremia at 25%; anaerobes account for less than 10%, and polymicrobial infections at 5% to 17%.⁴⁰E coli is the most commonly isolated bacteria, accounting for 22% to 54% of the cases, with other gram-negative isolates such as Klebsiella pneumoniae at 8% to 16% and pseudomonas at 4% to 14%, and gram-positives, such as S pneumoniae at 4% to 20%, S aureus at 4% to 14%, Enterococcus at 3% to 9%, and viridans streptococcus at 4%.⁴⁰S aureus bacteremia is more common in residents of LTCFs than in community-dwelling older adults. It is also associated with high mortality, at 20% to 37% in most studies.⁴¹

It has become increasingly evident that additional investigation of prognostic modeling is necessary, as the aging population is rapidly increasing. Prognostication of patients with pneumonia and sepsis can be particularly challenging. The Table summarizes biomarkers and scores used in the diagnosis and evaluation of severity of different infections in older adults.

The CURB-65 score, consisting of confusion, uraemia, respiratory rate of 30 breaths per minute, low blood pressure (BP), and age 65 years or older, has been validated in older adults,⁴² and it can indicate mortality and the appropriate setting for patient to receive care.⁴³ The Pneumonia Severity Index (PSI) is widely applied and risk-stratifies patients with CAP to determine whether patients can be treated as inpatient or outpatient. It includes parameters such as residence in NH, neoplastic disease, liver disease, congestive heart failure, cerebrovascular accident, renal disease, altered mental status, respiratory rate of more 29 breaths per minute, low BP, high temperature, fast pulse, serum urea nitrogen, pH, sodium plasma levels, glucose levels, hematocrit, and pleural effusion observed on x-ray. The PSI score was the best indicator predicting different clinical outcomes of older adult patients with CAP among pro B-type natriuretic peptide (NT-proBNP) test, CURB-65, and APACHE II.⁴⁴ Another score comparable to CURB-65 in assessing the severity of CAP is the A-DROP, which includes parameters such as sex, serum urea nitrogen greater than 210, respiratory failure/pulse oximetry, orientation disturbance, and low BP.⁴⁵ Another easy to use tool is the Quick Sepsis-related Organ Failure Assessment (qSOFA), which uses 3 criteria: low BP (<100 mm Hg), altered mentation (Glasgow coma scale <15), and tachypnea (>22 breaths per minute). It can be applied as an easy tool for quick bedside screening that predicts mortality, but it is lacking substantial validation.⁴⁶ Recent studies showed little use of qSOFA for the diagnosis of sepsis; only 24% of patient with confirmed diagnosis of sepsis fulfilled the qSOFA criteria. A lactate level of more than 2 mmol/L (18.02 mg/dL) is routinely used to assess mortality, and they are linearly associated with relative risk of mortality during hospitalization at 30 days and at 60 days, when compared with patients with a lactate level of less than 2. In studies, lactate has shown a better mortality association compared with a complete blood count or serum creatinine; however, this trend was irrelevant to infection.⁴⁷

The GYM score is a 30-day predictive mortality model in older adults who present to the emergency department with infection and is based on the criteria of a Glasgow score less than 15, tachypnea (>20 bpm), and Charlson Comorbidity Index score greater than 3. It is particularly accurate for patients older than 75 years of age.⁴⁸ Pro B-type natriuretic peptide levels are not only predictive of congestive heart failure, but they are also useful for risk stratification and prediction of mortality in CAP.⁴⁹ However, studies indicate NT-proBNP levels are not as good of a biomarker as PSI.⁴⁹ The use of serum urea nitrogen-to-albumin ratio can predict admission to the intensive care unit if high enough. However, low albumin itself can predict CAP.⁵⁰ A procalcitonin test (PCT) may also be helpful to identify severely ill older adults but not to discriminate patients with infection from those without. It is a particularly valuable diagnostic tool and can help characterize prognosis and severity of pneumonia in older adults.⁵¹ In a recent meta-analysis, the diagnostic accuracy of the PCT test was not inferior in older patients with sepsis compared with younger patients, hence not influenced by immunosenescence.⁵² In a study of older patients admitted to an acute geriatric care unit, a PCT level of 0.5 ng/mL was associated with an infection at admission together with other parameters studied. However, in the cases that the PCT test had good specificity (94%), it had low sensitivity (24%).⁵³ A false-negative PCT test was related to lower severity of infection (lower inflammatory reaction and lower acute renal failure) than a true-positive PCT test. In other studies, sensitivity and specificity of PCT to bacterial infection with the cut-off value of 0.5 ng/mL was 72% and 92%, respectively.⁵⁴

C-reactive protein (CRP) is another marker of inflammation that seems to rise 6 hours after infection and peaks at 48 hours, has a half-life of 19 hours, and is affected by immunosenescence but not by comorbidities. It can therefore be used for therapeutic monitoring. Rises are more sensitive than a PCT test but are less specific.⁵⁵ Lastly, the level of ischemia-modified albumin has been studied in the diagnosis of CAP in the emergency department and has so far shown promising correlation with CRP, with sensitivity of 75.3% and specificity of 92.3%.⁵⁶ For severity indicators of pneumonia and when comparing NHAP with CAP, it is apparent that NHAP has greater mortality based on patient characteristics and coexisting illnesses; pathogens differed. Of note, the existing and aforementioned severity indicators (ie, CURB-65, A-DROP, PSI) have less prognostic value for NHAP.⁵⁷

The rule “start low and go slow” is true for most drugs in older adults, but for antibiotics intending to treat serious infections, the rule changes. Older patients should receive a first antibiotic dose at the highest level with known safety profile, with subsequent dosing to maintain drug levels in the treatment range.⁵⁸ Patients with indwelling catheters or those who reside in a facility should have broad coverage based on their risk for resistant organisms. Broad coverage is detrimental in engendering resistance and increasing the risk of Clostridium difficile. Currently, the Centers for Disease Control and Prevention recommends an antibiotic time-out at 48 hours after initiating therapy and de-escalation to narrow spectrum treatment if culture results are available.⁵⁹

Empiric antibiotic selection in older patients with CAP, if seen on an outpatient basis, can be started on doxycycline, a macrolide, or a fluoroquinolone; however, if concerns for penicillin-resistant S pneumoniae infection arise, then a fluoroquinolone would be the antibiotic of choice. If aspiration pneumonia is suspected, amoxicillin/clavulanate potassium or a fluoroquinolone would be considered as first choice. For hospitalized patients, the antibiotic of choice is a cephalosporin with a macrolide or a beta-lactam/beta-lactamase inhibitor combined with a macrolide, or fluoroquinolone alone.⁶⁰

Oseltamivir is approved for treatment of influenza; however, it needs to be implemented within 48 hours of the onset of illness, which is difficult because most patients treat their illness at home for several days before seeking treatment from a physician.

Treatment of suspected UTIs should be directed to organisms identified by Gram stain and culture. Polymicrobial infections occur in about 30% of patients, more often in the setting of a catheter or recent broad-spectrum antibiotic use. Treatment of asymptomatic bacteriuria does not appear to reduce morbidity and mortality and may increase the likelihood of development of drug-resistant microorganisms and adverse reactions to antibiotics. Exceptions include patients scheduled for genitourinary procedures who have obstructive uropathy, stones, or a history of symptomatic infections.⁶¹ Older adults commonly present with MRSA. Vancomycin is the treatment of choice with or without gentamicin in cases of UTI and pneumonia. For VRE treatment, antibiotic choices vary by strain and resistance.⁶²

Prevention of infection in older adults is of prime importance. Undernutrition is common and has an adverse effect on the immune system. Both protein and micronutrient deficits affect immunity, with key players being zinc, selenium, folic acid, and vitamins C, E, B6, and B12; thus, supplementation is important to consider in this patient population.^63-66 Nutritional supplements have frequently been the focus of strategies to boost immune responses in clinical trials,⁶⁷ but randomized controlled trials with clinical end points are rare and often report conflicting findings.^68-70 Hence, controversy exists concerning every nutritional regimen tested to date. For example, while vitamin E deficiency is rare, intake above the recommended level has been shown to enhance T-cell function in aged animals and humans. This effect is believed to lead to increased resistance to influenza infection in animals and reduced incidence of upper respiratory infection in older adults. However, vitamin E is associated with adverse cardiac outcomes, namely heart failure, and caution is advised with its use. Zinc deficiency, common in older adults, is linked to impaired immune function and increased risk for acquiring infection, which can be rectified by zinc supplementation. However, higher than recommended upper limits of zinc may adversely affect immune function. Increased intake of fish or n-3 polyunsaturated fatty acids may be beneficial to inflammatory and autoimmune disorders, as well as to several age-related diseases. Conversely, the immunosuppressive effect of fish oils on T-cell–mediated function has raised concerns regarding their impact on resistance to infection. The studies published thus far describe a critical role for nutrition in maintaining the immune response of older individuals, but they also indicate the need for a more in-depth, holistic approach to determining the optimal nutritional strategies that would maintain a healthy immune system in older adults and promote their resistance to infection and other immune-related diseases. There are currently no discrete guidelines regarding supplementation, but the dominating notion is that supplementation may cause more harm than good, except for vitamin D and vitamin B12 if found low.

Immunization plays a key role in preventing infections. Vaccinations such as Tdap (tetantus, diphtheria, pertussis), pneumococcal, seasonal influenza, and zoster should be visited in all medical encounters. In the United States, 60% to 65% of older adults receive the pneumococcal vaccine and 70% to 75% receive the influenza vaccine.⁷² Immunization for influenza and pneumococcus are the most important preventive strategies. While pneumococcal vaccination may not prevent pneumonia in older adults, rates of bacteremia and invasive pneumococcal disease are decreased in immunized patients, and mortality in older patients hospitalized with pneumonia is lower for patients who were vaccinated before admission.⁷

In summary, infection risk in older adults is elevated because of immune deficiencies, comorbidities, and changes in environmental setting. These patients are highly likely to present atypically; thus, care needs to be taken in noticing subtle, vague changes in mental and functional status. Early identification of infection can prove life-saving in older adults because they are at high risk for poor outcomes.

Authors: Fotini Debonera, MD, PhD¹ • B Brent Simmons, MD FAAFP²

Affiliations:
¹Department of Family Medicine, Division of Geriatrics, UPMC Home Visits Program, Litiz, PA
²Department of Family, Community and Preventive Medicine, Division of Geriatrics,Tower/Drexel Medical group, Drexel University School of Medicine, Philadelphia, PA

Disclosures: 
The author report no relevant financial relationships.

Address correspondence to:
Fotini Debonera, MD, PhD
Department of Family Medicine
Division of Geriatrics
UPMC Home Visits Program
Litiz, PA
Email: deboneraf@upmc.edu