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Transcript
INFECTIOUS
DISEASES
OBJECTIVES
Know and understand:
• Factors that influence immune function in
elderly people
• Ways in which infectious diseases may present
atypically in older patients
• Criteria for initiating antibiotic therapy for
residents of long-term-care facilities
• How to diagnose and manage infectious
diseases that are common in the elderly
Slide 2
TOPICS COVERED
• Predisposition to infection
• General principles for diagnosis and
management of infections
• Epidemiology, diagnosis, and management
of specific infectious syndromes
• Fever of unknown origin
Slide 3
CONSEQUENCES OF INFECTION
• Mortality—Infection
is a major cause of
death in older adults
• Morbidity—Infection
often exacerbates
underlying illness
or leads to
hospitalization
Infection
40%
All
other
causes
60%
Major cause of death
in adults  65 years
Slide 4
AGE-RELATED ALTERATIONS
IN IMMUNE FUNCTION
• Immune response declines with age, a phenomenon
known as immune senescence
• The main features are depressed T-cell responses
and depressed T-cell/macrophage interactions
• The most marked deficits of immunity in the elderly:
 Drying and thinning of the skin and mucous membranes
 Poor antibody production
 Decreased production of IL-2 and T-cell “help”
Slide 5
IMPACT OF COMORBIDITY
ON IMMUNE FUNCTION
• The impact of comorbidities on innate immune
function and host resistance is greater than the
impact of age itself
• Comorbid diseases also indirectly complicate
infections (eg, community-acquired pneumonia
in an elderly person with multiple comorbidities
often requires hospitalization)
Slide 6
IMPACT OF NUTRITIONAL STATUS
ON IMMUNE FUNCTION
• On hospital admission, global undernutrition is
present in 30%–60% of patients 65 years
• 11% of older outpatients suffer from
undernutrition, mostly due to reversible conditions
such as depression, poorly controlled diabetes
mellitus, and medication side effects
• Some nutritional interventions may boost immune
function in older adults, but results vary with the
population studied and the supplements used
Slide 7
ATYPICAL PRESENTATION
• Older adults may present without typical signs and
symptoms, even if the infection is severe
• Fever may be absent in 30%–50% of frail older adults
with serious infections
• Fever in elderly nursing-home residents can be
redefined as:
 Temperature > 2°F (1.1°C) over baseline, or
 Oral temperature > 99°F (37.2°C) on repeated measures, or
 Rectal temperature > 99.5°F (37.5°C) on repeated measures
Slide 8
ANTIBIOTIC MANAGEMENT
• Drug distribution, metabolism, excretion, and
interactions can be altered with age
• Even in the absence of disease, aging is associated
with a reduction in renal function
• Antibiotic interactions occur with many medications
commonly prescribed for elderly people
• Risk factors for poor adherence include poor cognitive
function, impaired hearing or vision, multiple
medications, and financial constraints
Slide 9
SUGGESTED MINIMUM CRITERIA FOR
INITIATION OF ANTIBIOTIC THERAPY IN
THE LONG-TERM-CARE SETTING (1 of 2)
Condition
Minimum Criteria
Urinary tract infection,
without catheter
Fever AND one of the following: new or
worsening urgency, frequency, suprapubic
pain, gross hematuria, CVA tenderness,
incontinence
Urinary tract infection, with
catheter
Fever OR one of the following: new CVA
tenderness, rigors, new-onset delirium
Skin and soft-tissue infection
Fever OR one of the following: redness,
tenderness, warmth, new or increasing
swelling of affected site
Slide 10
SUGGESTED MINIMUM CRITERIA FOR
INITIATION OF ANTIBIOTIC THERAPY IN
THE LONG-TERM-CARE SETTING (2 of 2)
Condition
Minimum Criteria
Respiratory infection
 Fever > 102°F (38.9°C) AND RR > 25 or
productive cough
 Fever > 100 < 102°F AND RR > 25, pulse >
100, rigors, or new-onset delirium
 If afebrile but with COPD: new or increased
cough with purulent sputum
 If afebrile without COPD: new or increased
cough AND either RR > 25 or new-onset
delirium
Fever without source of
infection
 New-onset delirium or rigors
 If antibiotics instituted as a diagnostic test
(not recommended), discontinue in 3–5 days
if no improvement and evaluation negative
Slide 11
BACTEREMIA AND SEPSIS
• Elderly patients with bacteremia are less
likely than younger adults to have chills or
sweating, and fever is commonly absent
• GI and genitourinary sources of bacteremia
are more common than in younger adults
• Mortality rate with nosocomial gram-negative
bacteremia: 5%–35% in younger adults,
37%–50% in elderly patients
Slide 12
MANGEMENT OF BACTEREMIA
AND SEPSIS
• Similar in older and younger patients
• Rapid administration of antibiotics aimed at the
most likely sources is essential
• Early “goal-directed” therapy for volume
resuscitation has proven benefit
• In septic adults  age 75, adjunctive therapy with
activated protein C has a survival benefit despite
a slightly increased risk of serious bleeding
Slide 13
PNEUMONIA: EPIDEMIOLOGY
• Patients  65 account for over 50% of cases
• Cumulative 2-year risk for long-term-care
residents is about 30%
• Mortality in elderly patients is 3 to 5 that
of younger adults
• Comorbidity is the strongest independent
predictor of mortality
Slide 14
CAUSES OF PNEUMONIA
Slide 15
COMMUNITY-ACQUIRED PNEUMONIA
Infectious Diseases Society of America guidelines
suggest the following as first-line therapy for adults
over 60, with or without comorbidity:
• β-lactam/β-lactamase combination or advancedgeneration cephalosporin (ceftriaxone or
cefotaxime), with or without a macrolide
• Alternatively, one of the newer fluoroquinolones
with enhanced activity against S. pneumoniae
(levofloxacin, moxifloxacin, gemifloxacin)
Slide 16
NURSING HOME AND
HOSPITAL-ACQUIRED PNEUMONIA
• Initial regimens should be broadly inclusive, followed
by step-down therapy to narrower coverage if the
causative agent is identified
• For MRSA-colonized patients or patients in units with
high rates of MRSA, initial regimens should include
vancomycin or linezolid until MRSA is excluded
• Patients with improving hospital-acquired pneumonia
not caused by nonfermenting gram-negative bacilli
(eg, Pseudomonas, Stenotrophomonas) can receive
short courses of antibiotics (8 days)
Slide 17
REDUCING THE RISK OF PNEUMONIA
• Immunization
• Smoking cessation
• Aggressive treatment of comorbidities (eg,
minimizing aspiration risk in post-stroke
patients, limited use of sedative hypnotics)
• System changes with attention to infection
control may be particularly effective in the
nursing home
Slide 18
INFLUENZA
• Annual influenza vaccination is recommended for all
adults over 50
• Treatment with M2 inhibitors or neuraminidase
inhibitors is most effective if initiated within 24 hours
of symptom onset
• Oseltamivir (oral) is easier to use than zanamivir
(inhaled)
• Older adults appeared to be less susceptible to the
H1N1 pandemic of 2009 but are more likely to be
hospitalized for H1N1 than younger adults
Slide 19
URINARY TRACT INFECTION (UTI)
• One of the most common illnesses in older adults
• As in younger adults, gram-negative bacilli are most
common
• Older adults are more likely to have resistant isolates,
such as Pseudomonas aeruginosa, and gram-positive
organisms, including enterococci, coagulase-negative
staphylococci, and Streptococcus agalactiae
• Additional organisms in patients with indwelling
catheters include enterococci, S. aureus, and fungi,
particularly Candida spp.
Slide 20
ASYMPTOMATIC BACTERURIA
• Affects up to 15% of women in the community
and 40% of women in nursing homes
• Incidence in men is approximately half that in
women
• Treatment is not recommended
 No clinical benefit
 Associated with adverse effects, expense,
potential for selection of resistant organisms
Slide 21
LOWER-TRACT UTI (CYSTITIS)
IN OLDER WOMEN
• Characterized by dysuria, frequency, and urgency
• 3‒7 days of therapy sufficient for uncomplicated cystitis
• Fluoroquinolones (FQs) more efficacious than TMP-SMX
in recent trials (TMP-SMX resistance usually >10%–20%)
• Options in some settings are amoxicillin (particularly for
enterococcal infection) and first-generation
cephalosporins for patients with FQ intolerance
• Culture not required unless first-line therapy fails
Slide 22
UPPER-TRACT UTI (PYELONEPHRITIS)
IN OLDER WOMEN
• Characterized by fever, chills, nausea, and flank pain;
commonly accompanied by lower-tract symptoms
• Requires 7–21 days of therapy
• Consider IV antibiotics for patients with suspected
urosepsis, those with upper tract disease due to
relatively resistant bacteria such as enterococci, and
those unable to tolerate oral medications
• Culture and sensitivity data should be obtained in
most cases
Slide 23
UTI IN OLDER MEN
• Causative organisms and treatment choices are
similar to those for older women
• Usually due to obstructive prostatic disease or
functional disability; 14 days of therapy needed
• If prostatitis is suspected, 6 weeks of therapy is
usually required
• Culture and sensitivity data should guide therapy
for virtually all UTIs in older men
Slide 24
TUBERCULOSIS: EPIDEMIOLOGY
• Patients 65 account for 25% of active cases in US
• In long-term-care residents, prevalence of skin-test
reactivity is 30%–50%, due to high rates of
exposure in the early 1900s
• Thus, most active cases in older adults are due to
reactivation
• Primary infection is of particular concern in nursinghome outbreaks
Slide 25
TUBERCULOSIS: PRESENTATION
• Older adults may present with fatigue, anorexia,
decreased functional status, or low-grade fever
instead of classic symptoms
• Lung involvement common (75%); pneumonic
processes in older adults should raise suspicion
• Elderly patients are more likely than younger
adults to have extrapulmonary disease
• Virtually any body structure can be involved, and
that organ system can account for the major
presenting symptom
Slide 26
TUBERCULOSIS: SKIN TESTING
• Induration ≥15 mm 48 to 72 hours after placement of
a 5-tuberculin-unit PPD indicates a positive test in all
situations
• Induration ≥10 mm is considered positive in nursinghome residents, recent converters (previous PPD <5
mm), immigrants from countries with high endemicity
of TB, underserved US populations, and people with
specific risk factors
• Induration 5 mm is considered positive in HIVinfected patients, those with a history of close contact
with people with active TB, and those with chest
radiographs consistent with TB
Slide 27
TUBERCULOSIS: MANAGEMENT
• Treatment of active TB is similar to that in
younger adults
• Regardless of age, anyone with a positive PPD
should be treated with isoniazid for 9 months if:
 They have never been treated in the past
 Active disease is excluded
Slide 28
INFECTIVE ENDOCARDITIS
• In the elderly, associated with degenerative valvular
disorders and prosthetic valves
• Age does not increase mortality risk
• Treatment is IV antibiotics for 2–6 weeks
• Consider surgery for severe valvular dysfunction,
recurrent emboli, marked heart failure, myocardial
abscess, fungal endocarditis, or failure of antibiotics
to sterilize blood cultures
Slide 29
AHA GUIDELINES FOR
ENDOCARDITIS PROPHYLAXIS (1 of 3)
• Cardiac conditions requiring prophylaxis
 Prosthetic cardiac valve
 Previous infective endocarditis
 Cardiac transplant recipients with cardiac valvulopathy
 Unrepaired cyanotic congenital heart disease
 Repaired congenital heart disease with residual defects at the
site or adjacent to the site of a prosthetic patch or device
 Congenital heart disease completely repaired with prosthetic
material or device (prophylaxis needed for only the first 6 mo
after repair procedure)
Slide 30
AHA GUIDELINES FOR
ENDOCARDITIS PROPHYLAXIS (2 of 3)
• Procedures warranting prophylaxis (only in patients
with cardiac conditions listed on previous slide)
 Dental procedures requiring manipulation of gingival
tissue, manipulation of the periapical region of teeth,
or perforation of the oral mucosa (includes
extractions, implants, reimplants, root canals, teeth
cleaning during which bleeding is expected)
 Invasive procedures of the respiratory tract involving
incision or biopsy of respiratory tract mucosa
 Surgical procedures involving infected skin, skin
structures, or musculoskeletal tissue
Slide 31
AHA GUIDELINES FOR
ENDOCARDITIS PROPHYLAXIS (3 of 3)
• Procedures not warranting prophylaxis
 All dental procedures not listed on previous slide
 All noninvasive respiratory procedures
 All gastrointestinal and genitourinary procedures
Slide 32
ENDOCARDITIS
PROPHYLAXIS REGIMENS
Situation
Regimen (Single Dose 30–60 Min
Before Procedure)*
Oral
Amoxicillin 2 g po
Unable to take oral
medication
Ampicillin 2 g, cefazolin 1 g, or
ceftriaxone 1 g IM or IV
Allergic to penicillins or
ampicillin
Cephalexin 2 g, clindamycin 600 mg,
azithromycin 500 mg, or clarithromycin
500 mg po
Allergic to penicillins or
ampicillin and unable to
take oral medication
Cefazolin 1 g, ceftriaxone 1 g, or
clindamycin 600 mg IM or IV
Slide 33
PROSTHETIC DEVICE INFECTIONS
• Device removal usually required for cure
• Early and prolonged antibiotic intervention (for
months), combined with aggressive surgical
drainage, may be successful if symptoms have
been present only for a brief duration
• When full functionality is the goal, the best course
is device removal and administration of antibiotics
for 6–8 weeks, followed by reimplantation
• Administration of prophylactic antibiotics other than
for heart valves remains controversial
Slide 34
SEPTIC ARTHRITIS
• More likely in joints with underlying pathology
• Early arthrocentesis is indicated in any mono- or
oligoarticular syndrome, to exclude infection
• S. aureus is the most likely pathogen
• Aggressive antibiotic therapy should be combined
with serial arthrocentesis in uncomplicated cases
• Surgical drainage required when conservative
strategy fails
Slide 35
OSTEOMYELITIS
• S. aureus is the predominant organism
• GI and genitourinary flora are more common than
in younger adults, so a specific microbiologic
diagnosis is useful
• Infections of pressure ulcers and diabetic foot
infections commonly require surgical consultation
plus aggressive antimicrobial therapy aimed at
mixed aerobic and anaerobic bacteria
Slide 36
HIV INFECTION AND AIDS
• Heterosexual activity is the primary mode of infection
in older adults
• Untreated older adults progress to AIDS more rapidly
than young adults, but response to HAART is similar
• Management is similar to that used for younger adults,
except that more aggressive CVD prevention is
warranted
• HIV is probably the most treatable infectious cause of
dementia and much more likely to reverse with
therapy than syphilis (which is more commonly tested)
Slide 37
BACTERIAL MENINGITIS
• Older adults account for most meningitis-associated
fatalities
• Ceftriaxone or cefotaxime, plus vancomycin, are
recommended as empiric therapy until a specific
isolate can be tested for antimicrobial susceptibility
• Ampicillin is the drug of choice for Listeria spp.
• More resistant gram-negative rods (eg, Pseudomonas
spp.) require ceftazidime or an extended-spectrum
penicillin, with or without intrathecal aminoglycoside
therapy
Slide 38
NEUROSYPHILIS
• Possible underlying process in stroke or
dementia; also consider in unilateral deafness,
gait disturbances, uveitis, and optic neuritis
• Positive CSF serology (VDRL test) may be
diagnostic, but the sensitivity is only 75% in
most series
• Optimal treatment is penicillin G
Slide 39
REACTIVATED VARICELLA ZOSTER
VIRUS (HERPES ZOSTER, SHINGLES)
• Advancing age is the major risk factor
• The most disabling complication, postherpetic
neuralgia, is common in older adults
• Zoster vaccine is recommended for all
immunocompetent adults ≥ 60 yr old and
reduces the risk of zoster and post-herpetic
neuralgia by >50%
Slide 40
FACIAL NERVE PALSY (BELL’S PALSY)
• Associated with at least 3 infectious causes: herpes
simplex virus, varicella zoster virus, and Borrelia
burgdorferi (which causes Lyme disease)
• If facial nerve palsy occurs as part of an episode of
varicella zoster virus, antiviral treatment is indicated
and corticosteroids should be administered as well
• If Lyme disease is suspected on a clinical basis:
 Oral amoxicillin, 500 mg four times per day for 14 days; or
 Oral doxycycline, 100 mg twice per day for 14 days; or
 IV ceftriaxone, 2 g per day for 14 days
Slide 41
GASTROINTESTINAL INFECTIONS
• Can present diagnostic dilemmas in the absence of
fever or elevated WBC counts; a high index of
suspicion is necessary
• Diagnostic aids:
 Intra-abdominal infection—CT or labeled WBC study
 Cholecystitis, appendicitis, abscess—ultrasound
 Ischemic bowel—often requires angiography or
flexible sigmoidoscopy
• Treat infectious diarrhea as in younger adults
Slide 42
CLOSTRIDIUM DIFFICILE INFECTION
• Recent increase in incidence and severity,
especially in older adults
• First-line treatment:
 Metronidazole in mild to moderate disease
 Vancomycin in severe disease
• Relapse is more common in older adults and
may require tapering the vancomycin dose
• Prevention: Reduce unneeded antibiotics and
duration of needed antibiotic use
Slide 43
FEVER OF UNKNOWN ORIGIN
• Defined as temperature > 38.3°C (101°F) for at least 3
weeks, undiagnosed after 1 week of medical evaluation
• About 35% of cases are due to treatable infections,
especially intra-abdominal abscess, bacterial
endocarditis, and tuberculosis
• Collagen vascular diseases are more common causes
than in younger patients (about 30% of cases)
• Neoplastic disease accounts for another 20% of cases
Slide 44
EVALUATING FEVER OF UNKNOWN
ORIGIN IN OLDER ADULTS (1 of 2)
1. Confirm fever; conduct thorough history (include travel, MTB
exposure, drugs, constitutional symptoms, symptoms of giant cell
arteritis) and physical exam. Discontinue nonessential medications.
2. Initial laboratory evaluation: CBC with differential, liver enzymes,
ESR, blood cultures  3, PPD skin testing, TSH, antinuclear
antibody. Consider antineutrophilic cytoplasmic-antibody or HIVantibody testing.
3. a) Chest or abdomen or pelvic CT scan—if no obvious source; or
b) Temporal artery biopsy—if symptoms or signs are consistent with
giant cell arteritis or polymyalgia rheumatica and increased ESR; or
c) Site-directed work-up on basis of symptoms or laboratory
abnormalities, or both.
Slide 45
EVALUATING FEVER OF UNKNOWN
ORIGIN IN OLDER ADULTS (2 of 2)
4.
If 3a is performed and no source is found, then 3b, and vice versa.
5.
a) BM biopsy—yield best if hemogram abnormal—send for H&E,
special stains, cultures, or
b) Liver biopsy—very poor yield unless abnormal liver enzymes or
hepatomegaly.
6.
Indium-111 labeled white blood cell or gallium-67 scan—nuclear
scans can effectively exclude infectious cause of FUO if negative.
7.
Laparoscopy or exploratory laparotomy.
8.
Empiric trial—typically reserved for antituberculosis therapy in rapidly
declining host or high suspicion for tuberculosis (ie, prior positive
PPD).
Slide 46
SUMMARY
•
Immune function and host resistance are compromised
in elderly people as a consequence of both immune
senescence and comorbid disease
•
A redefinition of fever should be considered in the frail
older patient
•
There are suggested criteria for initiating antibiotic
therapy in residents of long-term-care facilities
•
Careful selection of first-line therapy is warranted in
older patients with pneumonia
Slide 47
CASE 1 (1 of 4)
• A 79-year-old man in an assisted-living facility has
cough, shortness of breath, and pleuritic chest pain.
• He has a history of heart failure with bifascicular block
and chronic kidney disease with a baseline creatinine
of 1.8 mg/dL.
• His medications are lisinopril, furosemide, and
simvastatin.
• On examination, he is awake and alert. Respiratory
rate is 22 breaths per minute, temperature is 39.2°C
(102.5°F), heart rate is 90 beats per minute, and blood
pressure is 130/80 mmHg.
Slide 48
CASE 1 (2 of 4)
• Chest auscultation reveals crackles in the left lower
lobe, and a chest radiograph shows an infiltrate.
Community-acquired pneumonia is diagnosed, and the
patient is admitted to the hospital.
• His creatinine is now 3.5 mg/dL, with an estimated
creatinine clearance of 20 mL/min.
• Sputum for gram stain is not obtainable; a urine for
Streptococcus pneumoniae and Legionella antigen
detection is sent.
Slide 49
CASE 1 (3 of 4)
Which is the most appropriate initial antibiotic
choice?
(A) Moxifloxacin 200 mg/d
(B) Ceftriaxone 1 gram/d plus azithromycin 500 mg/d
(C) Levofloxacin 750 mg/d
(D) Aztreonam 2 grams q8h plus vancomycin 1 gram q24h
Slide 50
CASE 1 (4 of 4)
Which is the most appropriate initial antibiotic
choice?
(A) Moxifloxacin 200 mg/d
(B) Ceftriaxone 1 gram/d plus azithromycin 500 mg/d
(C) Levofloxacin 750 mg/d
(D) Aztreonam 2 grams q8h plus vancomycin 1 gram q24h
Slide 51
CASE 2 (1 of 3)
•
A 78-year-old man comes to the office because he
volunteers at the local hospital and is required to get
a tuberculin skin test annually.
•
A tuberculosis skin test (PPD) using 5 tuberculin
units was done a year ago when he started
volunteering. At that time, the test was read as 4 mm
of induration and interpreted as negative.
•
On retesting now, there is 16 mm of induration. He
has no symptoms, and chest radiograph is negative.
He is on warfarin for atrial fibrillation but has no other
problems and no other medications.
Slide 52
CASE 2 (2 of 3)
What is the most appropriate next step in
management?
(A) Observation only
(B) Annual chest radiography
(C) Repeat PPD testing in 6 mo
(D) Treatment with pyrazinamide plus rifampin for 2 mo
(E) Treatment with isoniazid for 9 mo
Slide 53
CASE 2 (3 of 3)
What is the most appropriate next step in
management?
(A) Observation only
(B) Annual chest radiography
(C) Repeat PPD testing in 6 mo
(D) Treatment with pyrazinamide plus rifampin for 2 mo
(E) Treatment with isoniazid for 9 mo
Slide 54
CASE 3 (1 of 3)
• A 72-year-old man is seen for preoperative
assessment in anticipation of a prostate biopsy.
• He has asymptomatic aortic stenosis with a stable
III/VI holosystolic murmur and type II diabetes
mellitus controlled by diet.
• He is allergic to penicillin but has taken cephalexin or
clindamycin for dental procedures in the past without
difficulty.
Slide 55
CASE 3 (2 of 3)
Which of the following is the most appropriate
recommendation regarding endocarditis
prophylaxis for the biopsy?
(A) No prophylaxis
(B) Oral cephalexin
(C) Intravenous cefazolin
(D) Oral cephalexin plus oral clindamycin
(E) Intravenous cefazolin plus intravenous clindamycin
Slide 56
CASE 3 (3 of 3)
Which of the following is the most appropriate
recommendation regarding endocarditis
prophylaxis for the biopsy?
(A) No prophylaxis
(B) Oral cephalexin
(C) Intravenous cefazolin
(D) Oral cephalexin plus oral clindamycin
(E) Intravenous cefazolin plus intravenous clindamycin
Slide 57
ACKNOWLEDGMENTS
Editor:
Annette Medina-Walpole, MD
GRS7 Chapter Author
and Question Writer:
Kevin Paul High, MD, MSc
Pharmacotherapy Editor:
Judith L. Beizer, PharmD
Medical Writers:
Beverly A. Caley
Faith Reidenbach
Managing Editor:
Andrea N. Sherman, MS
Copyright  2010 American Geriatrics Society
Slide 58