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1 INFECTIOUS DISEASES 2 OBJECTIVES Know and understand: • Factors that influence immune function in older adults • 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 older adults 3 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 4 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 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 • B cells produce antibodies with lower affinity weakened immunogenicity of vaccines 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 older adult with multiple comorbidities often requires hospitalization) 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 7 8 LONG-TERM CARE CONSIDERATIONS • Residence in a nursing facility puts older adults at risk of epidemic diseases such as influenza • Widespread antibiotic use increases likelihood of infection by antibiotic-resistant organisms • Resistance issues are worsened by: Debilitated host Close proximity of residents Poor staff compliance with prevention strategies (eg, influenza immunization) Difficulties with infection control implementation • Maintaining up-to-date immunizations is critical 9 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 older 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 10 ANTIMICROBIAL 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 older adults • Risk factors for poor adherence include poor cognitive function, impaired hearing or vision, multiple medications, and financial constraints 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 CVA = costovertebral angle SUGGESTED MINIMUM CRITERIA FOR INITIATION OF ANTIBIOTIC THERAPY IN THE LONG-TERM-CARE SETTING (2 of 2) Condition Respiratory infection Minimum criteria 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 New-onset delirium or rigors infection If antibiotics instituted as a diagnostic test (not recommended), discontinue in 3–5 days if no improvement and evaluation negative 13 BACTEREMIA AND SEPSIS • Older 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 older patients 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 14 15 PNEUMONIA: EPIDEMIOLOGY • Patients 65 account for over 50% of cases • Cumulative 2-year risk for long-term-care residents is about 30% • Mortality in older patients is 3 to 5 that of younger adults • Comorbidity is the strongest independent predictor of mortality CAUSES OF PNEUMONIA IN O L D E R A D U LT S • Streptococcus pneumoniae predominates • Gram-negative bacilli (eg, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella spp.) are more common than in younger adults, particularly in those with COPD and nursing home residents • Staphylococcus aureus and respiratory viruses commonly cause community-acquired pneumonia in nursing-home residents 16 17 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) 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) 18 19 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 20 INFLUENZA • Annual flu vaccination is recommended for all adults FDA approved high-dose vaccine for adults ≥ 65 yr, which produces higher antibody responses, but unknown if this provides better clinical protection • Treatment with neuraminidase inhibitors is most effective if initiated within 48 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 21 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. 22 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, C. difficile colitis, and potential for selection of resistant organisms LOWER-TRACT UTI (CYSTITIS) IN OLDER WOMEN 23 • 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 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 24 25 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 26 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 27 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 • Older 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 28 TUBERCULOSIS: SKIN TESTING • Induration ≥15 mm 48 to 72 hours after placement of a 5-tuberculin-unit PPD is 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, patients with a history of close contact with people with active TB, and those with chest radiographs consistent with TB 29 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 30 INFECTIVE ENDOCARDITIS • In older adults, associated with degenerative valvular disorders and prosthetic valves • Treatment is IV antibiotics for 4–6 weeks • Consider surgery for severe valvular dysfunction, recurrent emboli, marked heart failure, myocardial abscess, fungal endocarditis, or failure of antibiotics to sterilize blood cultures 31 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 32 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 33 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 34 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) 35 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 36 NEUROSYPHILIS • Possible underlying process in stroke or dementia; also consider in unilateral deafness, gait disturbances, uveitis, and optic neuritis • Positive CSF serology (Venereal Disease Research Laboratory test) may be diagnostic, but the sensitivity is only 75% in most series • Optimal treatment is penicillin G 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% 37 38 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 4 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 39 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 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: Avoid unneeded antibiotics and reduce duration of needed antibiotic use 40 41 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 one third 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 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. 42 EVALUATING FEVER OF UNKNOWN ORIGIN IN OLDER ADULTS (2 of 2) 43 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). 44 SUMMARY • Immune function and host resistance are compromised in older adults 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 45 CASE 1 (1 of 4) • A 78-year-old man is admitted to the hospital because he has had cough, shortness of breath, and fever for the past 3–4 days. • He was hospitalized 3 months ago for a similar episode; at that time he was treated with ceftriaxone and doxycycline. • History includes hypertension, hyperlipidemia, and mild cognitive impairment. 46 CASE 1 (2 of 4) • Temperature is 38.1°C (100.6°F) and blood pressure is 155/80 mmHg. Heart rate is 101 beats per minute, respiratory rate is 22 breaths per minute, and O2 saturation is 95% on 2 L of oxygen via nasal cannula. • Radiography of the chest shows bilateral lower lobe infiltrates. • Laboratory results are normal except for WBC count of 15,700/μL and creatinine level of 1.0 mg/dL. • On admission, the diagnosis is community-acquired pneumonia. 47 CASE 1 (3 of 4) Which of the following antibiotics would be most effective? A. Ceftriaxone B. Levofloxacin C. Ceftriaxone plus doxycycline D. Azithromycin E. Doxycycline 48 CASE 1 (4 of 4) Which of the following antibiotics would be most effective? A. Ceftriaxone B. Levofloxacin C. Ceftriaxone plus doxycycline D. Azithromycin E. Doxycycline 49 CASE 2 (1 of 3) • A 67-year-old man is preparing to undergo colonoscopy with polypectomy for a polyp detected on recent capsule endoscopy. • History includes coronary artery disease and aortic valve stenosis. • The patient experiences hives when he takes penicillin. He does not recall whether he has taken cephalosporins in the past. 50 CASE 2 (2 of 3) Which of the following is most appropriate in terms of endocarditis prophylaxis for this patient? A. Oral clindamycin B. Oral azithromycin C. Oral moxifloxacin D. Intravenous cefazolin E. No prophylaxis 51 CASE 2 (3 of 3) Which of the following is most appropriate in terms of endocarditis prophylaxis for this patient? A. Oral clindamycin B. Oral azithromycin C. Oral moxifloxacin D. Intravenous cefazolin E. No prophylaxis 52 CASE 3 (1 of 3) • In January, a 73-year-old nursing-home resident is evaluated because he has had fever, headache, nasal congestion, nonproductive cough, shortness of breath, and malaise since the previous day. • A rapid influenza test from a nasal swab is positive for influenza A. • Another resident has had similar symptoms for 2 days. 53 CASE 3 (2 of 3) Which of the following should be offered to the other nursing-home residents? A. Rimantadine B. Amantadine C. Oseltamivir D. Zanamivir E. Peramivir 54 CASE 3 (3 of 3) Which of the following should be offered to the other nursing-home residents? A. Rimantadine B. Amantadine C. Oseltamivir D. Zanamivir E. Peramivir 55 GRS Slides Editor: Annette Medina-Walpole, MD, AGSF GRS8 Chapter Authors: H. Keipp Talbot, MD, MPH Kyle Widmer, MD GRS8 Question Writer: Vera P. Luther, MD Medical Writers: Beverly A. Caley Faith Reidenbach Managing Editor: Andrea N. Sherman, MS Copyright © 2013 American Geriatrics Society SlideSlide 55 55