Infections in Older Adults

Souha Kanj, MD, FACP, FIDSA, FRCP, FECMM, FESCMIProfessor of Medicine, Head Division of Infectious Diseases,

Chair Infection Control and Prevention Program, AUBMCConsultant Professor, Duke University Medical Center, NC, USA

Outline

Aging populations Burden of infections in the elderly

Influence of aging on infection

Antimicrobial characteristics in the elderly

Antimicrobial use at end of life

Specific infections in the elderly

Immunization of older adults Wrap-up

Outline

Aging populations

Changing Population Demographics

2015• 617 million

people > 65 y• 8.5% of world

population

2050• 1.6 billion

people > 65 y• 16.6% of world

population

He W. US Census Bureau; 2016Bartels SJ. N Engl J Med 2013;368:493

Comparative Population Pyramids

Definition of the “Older Adult”

• Changes over time• Generally accepted to be older than 65 years in developed

countries• United Nations definition: 60+ years• WHO definition in Africa: 50+ years• Recognition of age subsets:– Young old (65-74 y)– Old (75-84 y)– Old-old (85+ y)

Outline

Burdenofinfectionsintheelderly

Burden of Infections in the Older Adult

• 2 of the top 10 leading causes of death in older adults directly related to infection– Influenza and pneumonia (infection of the lungs)

– Septicemia/bacteremia (bacteria in the blood)

• Older adults account for up to ¼ of all ED visits• Most frequent infections:

– Pneumonia (25%)

– Urine infection (22%)– Sepsis and bacteremia (18%)

• Visit ED more frequently than younger adults

Higher level of medical

acuity

Higher rates of test use

Longer durations of

ED stays

Higher rates of hospital admissions

More serious medical illnesses

Samaras N. Ann Emerg Med 2010;56:261

Outline

Influence of aging on infection

Aging and Risk of Infection

Inner factors

Changes in immunity

Organ-specific physiologic changes

Frailty

Factors influencing presentation of infection

Temperature regulation

Decline in mental abilities

Malnutrition

Changes in Immunity

• Age-related dysfunction of the immune system which leads to enhanced risk of infection

• Total no. of immune cells stable

• But…

• Functional decline in immunity

Gavazzi G. Lancet Infect Dis 2002;2:659

Changing Immunity

Reduced activity of cells that fight infections

Types of white cells

Increase in proteins that cause inflammation

Poor appetite, nutritional compromise, muscle weakness,

weight loss

Clegg A. Lancet 2013;381:752Qu T. Cytokine 2009;46:319

Heppner HJ. Crit Care Clin 2013;29:757Franceschi C. J Gerontol A Biol Sci Med Sci 2014;69:S4-9

Limitedantibodyresponsetoforeignproteinsofinfecting

bacteriaandviruses

Age-Related Physiologic ChangesOrgan system Physiologic changesUrinary ↓ bladder capacity and urinary flow, ↑ bacterial attachment, bladder

prolapse, prostatic enlargement, ↓ estrogen after menopause

Lungs ↓ cough reflex and clearance of cilia, chest compliance, lung muscle strength, and antibodies against bacteria and viruses in secretions

Skin Loss of tissue, slower wound healing, dry skin, ↓ size of blood vessels decrease delivery of cells that fight infection

Gastrointestinal ↓ saliva production, alteration in proteins in saliva, slower swallowing, ↓ gastric acidity, ↓ intestinal motility, changes in gut residing bacteria

Brain Structural and functional changes to brain cells

Glands ↑ cortisol, ↑ catabolism lead to poor appetite, weight loss, and ↓ muscle mass

Muscles Loss of muscle mass leads to ↓ strength and functionality

El Chakhtoura NG. Infect Dis Clin N Am 2017;31:593

• Affects up to 1/3 in 80+ years

• definition as 3 or more of :

– Unintended weight loss

– Exhaustion

– Weakness

– Slow gait speed

– Low physical activity

• Other clinical features: falls, delirium, fluctuating disability

• All may overlap with presentation of infections

• Vulnerability for subsequent problems becomes significant, triggered even by minor stressors

Frailty

Theou O. Ageing Res Rev 2015;21:78Fried LP. J Gerontol A Biol Sci Med Sci 2001;56:M146

Temperature Regulation

• Temperature regulation:

– Mean body T° ↓ with age, “the older, the colder”

– Fever predicting infection: 70% at 37.8°C– ↑ T° over baseline, occurs in most cases of infection in older adults

• Fever definition in older adults :

– Single oral T° > 37.8°C– Repeated oral T° > 37.2°C or rectal T° > 37.5°C– ↑ T° > 1.1°C over the baseline T°

Norman DC. Clin Infect Dis 2000;31:148Castle SC. Aging Immunol Infect Dis 1993;4:67

Mounting a fever is part of health defense and

absence of fever in response to a serious

infection is a poor sign

High KP. J Am Geriatr Soc 2009;57:375Kluger MJ. Infect Dis Clin North Am 1996;10:1

Decline in Mental Abilities

• In pneumonia, nonspecific presenting symptoms (e.g. generalized weakness, decreased appetite, falls, and delirium) more common in patients > 65 y

• When subjects with dementia were excluded, nonspecific symptoms similar in both groups

– Dementia, not age, explained the difference in clinical presentation of pneumonia

Johnson JC. J Am Geriatr Soc 2000;48:1316Schmidt R. Ann Neurol 2002;52:168

Malnutrition

• Affects 30% of older adults

• More prevalent in institutionalized and hospitalized individuals

• Related to depression, dental problems, disturbances of smell and taste, increased catabolism

• ↑ predisposition to infection

• Partially remediable with nutritional formulas:– ↑ influenza vaccine response

– Less fever

– Fewer newly prescribed antibiotics

Sanford AM. Curr Opin Clin Nutr Metab Care 2017;31:54Langkamp-Henken B. J Am Geriatr Soc 2006;54:1861Carlsson M. J Nutr Health Aging 2013;17:186

Aging and Risk of Infection

Environmental factors

Place of residence

Inappropriate antibiotic use

Place of Residence

• In the United States, approximately 1.4 million people reside in nursing homes:– Nursing home residents share dining, recreation and therapeutic

facilities

– Highly dependent upon health care workers (HCWs) for assistance with daily activities

– Frequent patient transfers between nursing homes and hospitals

• Spread of resistant bacteria (that are difficult to treat with antibiotics) from one setting to the other

Harris-Kojetin L. Vital Health Stat 3 2016;38:1

Outline

Antibiotics Characteristics in the elderly

Special Considerations of Antibiotic Use in the Elderly

• Frail old patients are especially susceptible to the toxic effects of antibiotics because of diminished reserve:– ↓ baseline function of ≥ 1 organs

– ↑ incidence of chronic diseases

– Polypharmacy (↑ in adverse effects and drug interactions)

• Delayed and inadequate dosing of drugs correlates with development of resistance and death

Bellmann-Weiler R. Gerontology 2009;55:241Hubbard RE. Eur J Clin Pharmacol 2013;69:319

Age-Related Changes

Drug Parameters

Excretion

Absorption

Distribution

Metabolism• ↓ stomach acidity• ↓ intestinal blood flow • ↓ stomach emptyingSlower rate but no significant ↓ in absorption

Benson JM. Infect Dis Clin N Am 2017;31:609

Drug Parameters

Excretion

Absorption

Distribution

Metabolism

Age-Related PK Changes

Age-related ↓ in total body water volume of some drugsInitiate a full initial dose then adjust for kidney function for subsequent doses

Benson JM. Infect Dis Clin N Am 2017;31:609

Drug Parameters

Excretion

Absorption

Distribution

Metabolism

Age-Related PK Changes

Metabolism ↓ with age↑ concentration of drugs taken by mouth

Benson JM. Infect Dis Clin N Am 2017;31:609

Drug Parameters

Excretion

Absorption

Distribution

Metabolism

Age-Related PK Changes

↓ kidney elimination↑ blood concentration of drugs eliminated by the kidneysNeed to monitor blood levels when possible

Benson JM. Infect Dis Clin N Am 2017;31:609

Considerations in the Older Adult

For some drugs

• Decrease the dose• Maintain or increase dosing frequency

For other drugs

• Maintain same dose• Decrease dosing interval

Benson JM. Infect Dis Clin N Am 2017;31:609

Outline

Antibiotic use at end of life

Overuse of Antibiotics at End of Life

• Up to 88% of patients receive abx in the final weeks of life!!!• No documented infection in 40-80%

• Noninfectious fever important reason to initiate abx• Abx one of the last interventions to be withdrawn or withheld

in terminally-ill patients• Perceived to carry a lower potential for harm

Baghban A. Infect Dis Clin N Am 2017;31:639

Goals, Benefits, and Harms of Antibiotics

Goals

↑ survival (lung

infection)

Symptom relief (urine infection)

Benefits

Improvement of psychological

distress

Alleviate pain (Oral Herpes, or

fungus )

Harms

Inflamed veinsbacteremia,

restraints

Toxicity, drug interactions

Diarrhea

Antibiotic resistance

Cost

Baghban A. Infect Dis Clin N Am 2017;31:639

Proposed Algorithm for Treatment

Baghban A. Infect Dis Clin N Am 2017;31:639

Outline

Specific infections in the elderly

Urine

Lung

Influenza

Shingles

Diarrhea

HIVSTDs

Select Infections in the Older Adult

Urinary Infection and Bacteria without symptoms

• Differentiating infection from bacteria in cultures without symptoms (up to 50% in nursing home residents) to avoid unnecessary abx

• Testing for infection only when clinical symptoms are present and exclude other causes

– difficulty in passing urine, frequency, pain, blood in urine, tenderness, new or worsening urgency or incontinence ± fever, chills, change in mental status

– Unreliable factors: falls, confusion, lethargy, urine turbidity, sediment color, odo

Warren JW. JAMA 1982;248:454

Loeb M. Infect Control Hosp Epidemiol 2001;22:120

St John A. Am J Clin Pathol 2006;126:428

Cortes-Penfield NW. Infect Dis Clin N Am 2017;31:673

• Leading cause of death among old patients

• > 40% of hospitalizations • 4 fold ↑ risk > 65 y vs. < 45 y• > 80% require hospitalization• Unidentified bacteria in 77% of

patients• Longer list of bacteria than in young

patients

• Predictors of death:– Residence in nursing home– stroke– Liver disease– Immunosuppression– Malnutrition– Severe pneumonia – Hospital admission

Bacterial Pneumonia (Lung Infection)

Henig O. Infect Dis Clin N Am 2017;31:689

Bacterial Pneumonia:Diagnosis

• Mental status changes might be the only sign

• Pneumonia should be considered with any of: – confusion, delirium, disorientation, loss of appetite, urinary

incontinence, recurrent falls, functional decline, exacerbation of underlying illnesses, low oxygen

• Imaging may be inadequate: Chest X Ray inconclusive

• Blood cultures, sputum culture before antibiotics

Henig O. Infect Dis Clin N Am 2017;31:689

• Many deaths from influenza due to pneumonia or cardiac complications

• Much more common in older adults

• Can spread easily among elderly patients

• 67% become housebound, 1/4 are bedbound

• Classic symptoms

• fever, cough, general aches for 3-7 d

• Presentation in elderly neither classic nor simple

– Only 40-65% fever

– 94% runny nose

– Shortness of breath

– Exacerbation of heart failure

– Exacerbation of bronchitis

• Rapid test positivity as low as 19%

Influenza in the Elderly

Talbot HK. Infect Dis Clin N Am 2017;31:757

• Elderly are candidates for

treatment

• Within 48 h of symptom onset

– Tamiflu

– Flumivir in Lebanon

• Benefits:

– Symptom relief

– ↓ hospital hospital length of

stay

– ↓ death

• Response to vaccination lower in

older patients

• Vaccine efficacy > 50 y 40-60% to

prevent hospitalization when

strains are similar

• 2 licensed vaccines for patients ≥

65 y in the US

1. High dose vaccine

2. MF59 adjuvanted vaccine

• Antiviral prophylaxis after

exposure

Treatment and Prevention of Influenza

Talbot HK. Infect Dis Clin N Am 2017;31:757

Lifetime incidence20-30%

By 80 y, lifetime incidence 50%

Impact of Shingles/Zoster and Post Zoster Pain (PHN)

Risk of PHN5-30%

By 85 y, risk of PHN 50%

Other complications beyond 50 y:vessel damage causing stroke, bleeding, vision loss,

local neurologic deficits

John AR. Infect Dis Clin N Am 2017;31:811

Locations of Shingles

Zoster Vaccines

Live attenuated

vaccineZostavax®

Same virus as chicken pox at 14-fold

↓ HZ by 50%

↓ PHN by 66%

Not for pts with ↓ immunity;

efficacy disappears with

time

Recombinant vaccine

Shingrix®

VZV protein + adjuvant

↓ HZ by 96%

↓ PHN by 89%

Efficacy remains; Muscle

discomfort

≥ 60 y

≥ 50 y

John AR. Infect Dis Clin N Am 2017;31:811

Coming to AUBMC soon

• Elderly are at higher risk

– have ↓ stomach acidity

– ↓ defenses

• Diarrhea can be due to

– Virus

– Bacteria

– Parasites

– Drug side effects including a bacteria from taking antibiotics (Clostridium difficile)

Diarrhea can lead to :• Fever• Belly pain• Dehydration• Kidney injury from dehydration If diarrhea persists we need to know the cause• Implications for:

– Testing– Treatment

• (antibiotics versus no)– Need for isolation

Diarrhea in the Elderly

HIV & Other Sexually Transmitted Diseases (STDs) In Old Age

• Keep an open mind• Life expectancy in elderly with HIV infection lags by

5 y• Medical problems develops ~ 10 y earlier• Other risk factors that accelerate aging: smoking,

substance abuse, viral coinfections, depression• Currently few old patients in my clinic with HIV and

are doing very well– One is 88 year old !!

• If painful genital ulcers consider herpes infection• If ulcers with no pain consider syphilis

Van Epps P. Infect Dis Clin N Am 2017;31:791

Outline

Vaccines of older adults

Meningitis for Hajj and Umrah, Yellow fever for Africa, Typhoid for India, etc..

Recommended Vaccines Schedule ≥ 65 Years

1 dose every yearInfluenza

1 dose then every 10 yTetanus/Diphtheria

2 doses RZV* or 1 dose ZVLShingles

1 dose of prevnar 13 and 1 dose of Pneumovax after 8 weeks-1 yearPneumonia

Travel vaccines

Advisory Committee on Immunization Practices. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html

Key Messages

• Old people are at higher risk for infections• Infections can lead to serious complications including death• The presentation of infections is different than in younger people• Antibiotics have different properties in older people and variation in

choice, dose, duration should be monitored• Overuse of antibiotics can lead to resistant bacteria and diarrhea

– Treat when symptoms happen not for positive culture• Prevention is important• Eat well, exercise• Update vaccination