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Infectious Disease of the Elderly

Instructor: Lynne Kallenbach, MD
Developed by: Kathryn Twenter, DO
Reviewed by: Doug Woolley, MD, MPH

 

Specific Learning Objectives

A. Introduction

Before reviewing the learning objectives and content, please take the Pre-Test.

Please review the Objectives, Content material, and Cases before our class session. We will apply the tasks in the Skills Objectives to these cases, and you should think about them ahead of time.

B. Attitudes - medical students will:

• Recognize that infectious diseases are a common cause of functional decline in the older adult.
  

C. Knowledge - Medical students should be able to:

• Recognize atypical presentations of infection in the elderly.
• Recognize that therapy and management of infectious diseases may be altered by age related changes and comorbidity.
• Recognize appropriate indications for certain vaccinations.

D. Skills - Medical students should be able to:

• Develop a comprehensive differential diagnosis for fever in an older adults
• Develop a diagnosis and treatment plan for infectious endocarditis and pneumonia.

E. Readings

Additional resources and readings are suggested at the end of each section.

F. Module Content

1. Epidemiology
2. Pathophysiology
3. Generalized Assessment and Management
4. Bacteremia and Sepsis
5. Pneumonia
6. Influenza
7. Urinary Tract Infection
8. Gastrointestinal Infections
9. Infective Endocarditis
10. Tuberculosis
11. Herpes Zoster
12. Miscellaneous
13. Fever of Unknown Origin (FUO)
14. References

G. Cases

• Case #1
• Case #2
• Case #3

 

I. EPIDEMIOLOGY

In those over the age of 65, infection accounts for 40% of all deaths.  There is a mortality rate increase by nine times as compared to those between the ages of 25 to 44.  (see chart)

II. PATHOPHYSIOLOGY

• Immune senescence is an age related phenomenon due to lack of cell proliferation, specifically lack of lymphocyte proliferation
• Contributors to deficits of immune response in the elderly:
  • Drying and thinning of the skin and mucous membranes
  • Poor antibody production
  • Decreased production of IL-2  and T-“helper” cells leading to decreased lymphocyte stimulation
  • Comorbid diseases can increase susceptibility to infections in the elderly, especially in the acute hospitalized setting
• Local barriers are altered due to poor mucociliary clearance and breakdown in skin integrity.
• Malnutrition can occur as a result of conditions such as depression, uncontrolled diabetes mellitus or medication side effects
  • 30-60% of those over the age of 65 will have both protein and calorie malnutrition
  • Malnutrition leads to poor vaccine response, impaired wound healing and increased risk of nosocomial infection

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III. GENERALIZED ASSESSMENT AND MANAGEMENT

• Atypical presentation of the infected elderly

Fever may be absent in 30-50% due to altered thermoregulation with blunted heat production by adipose tissue.  In the elderly, a temperature greater than 99 degrees F (37.2 degrees C) increases sensitivity to diagnose a fever as compared to temperature of 101 degrees F (38.3 degrees C) in younger patients.

Absence of fever does not rule out infection and presence of fever does not validate it. The AMDA (American Medical Directors Association) Clinical Practice Guideline for Infections in Long Term Care cite these criteria for fever in LTC:

• Increase from baseline > 2 F or 1, 1 C
• 2 or more oral temps of 99 F or 37.2 C
• 2 or more rectal temps 99.5 F or 37.5 C
• Single oral temp of > 100

Additional atypical features of infection include poor oral intake, fatigue with acute withdrawal from typical activities of interest, increased agitation and frequent confusion with associated delirium.  If they begin to have new or more frequent falls, then this may also be an additional atypical presentation of infection.

• Antibiotic Therapy

It is important to consider altered pharmacokinetics with aging due to altered volume of distribution, metabolism and excretion.  In addition, it is important to consider possible drug interactions between antibiotics and medication such as digoxin, warfarin, oral hypoglycemics, theophylline, antihypertensive medications, antacids and H2 receptor antagonists

Initial antibiotic choice must be broad to cover the appropriate organisms. The decision to initiate antibiotics must follow specific minimum criteria (see table) to avoid inappropriate use in the noninfectious or colonized settings.

Suggested Reference:  Minimum Criteria for Initiation of Antibiotic Therapy in the Long Term Care Setting (Source:  Loeb M, et al. Development of minimum criteria for initiation of antibiotics in residents of long term care facilities:  results of a consensus conference.   Infect Control Hosp Epidemiol.  2001;22:120-124.)

Infectious Condition	Minimum Criteria for Initiation of Antibiotic Therapy in the Long Term Care Setting
UTI (without foley catheter)	Fever AND one of the following:  new or worsening urgency, frequency, suprapubic pain, gross hematuria, CVA tenderness, incontinence
UTI (with foley catheter)	Fever OR one of the following: new CVA tenderness, rigors, or new onset delirium
Skin & Soft tissue infection	Fever OR one of the following:  redness, tenderness, warmth, new or increasing swelling of affected site
Respiratory infection	Fever> 102 F (38.9 C) AND one of the following:  RR>25, productive cough Fever >100 F  <102 F AND one of the following:  RR>25, pulse >100, rigors, new onset delirium Afebrile with COPD AND new or increased cough with purulent sputum Afebrile without COPD AND new or increased cough AND either RR> 25 or new onset delirium
Fever without source of infection	At least one of the following:  new onset delirium, rigors If these are not present, evaluate without initiating antibiotics Antibiotics probably should not be instituted as a diagnostic test, but if initiated as such, discontinue in 3-5 days if no improvement and evaluation is negative

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IV. BACTEREMIA AND SEPSIS

• This condition is a common cause of hospitalization for older patients with an associated poor prognosis; for example, nosocomial gram negative bactermia has a mortality rate up to 50% in the elderly as compared to 35% in young adults. Gastrointestinal and genitourinary sources are common causes of bacteremia in the elderly.
  
  
• Treatment

In addition to blood pressure support and source directed antibiotics, one could consider activated protein C, with support of a recent analysis in those over the age of 75 who demonstrated a survival benefit with only a slightly increased risk of serious bleeding. 

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V. PNEUMONIA

• Epidemiology

Patients over the age of 65 years account for 50% of all pneumonia cases.  A long term care resident has a 30% risk of developing pneumonia over a 2 year period. The fatality rate may be as high as 23%.

• Organisms

Common bacterial sources include Streptococcus pneumoniae, gram negative bacilli (Haemophilus influenza, Moraxella catarrhalis, Klebsiella), Staph aureus.  There is increased prevalence of drug resistant S. pneumoniae.

• Clinical presentation
  • Fever with cough productive of sputum
  • Confusion or mental status changes
  • Radiographically, patients can have multiple presentations based on the offending etiologic organism with potential complicating condition.  Bacterial pneumonia can present with either bronchopneumonia, lobar pneumonia, or other locations on lung x-ray or computed tomography.  Viral pneumonia can present as bilateral interstitial infiltrates.  Aspiration pneumonia can be localized to either the right middle lobe or it may have diffuse involvement. 

(see images: Bronchopneumonia CT, Aspiration Pneumonia X-ray)

• Treatment

Community acquired pneumonia can be covered with beta lactam with beta lactamase inhibitors or cephalosporin (ceftriaxone or cefotaxime) with or without a macrolide.  In the outpatient setting, long term care residents or those with severe COPD (FEV1 <30%) present the greatest risk of drug resistant S. pneumonia.  They benefit from fluoroquinolones such as levofloxacin, sparfloxacin, or moxifloxacin.

Nursing home acquired pneumonia can occur as a result of aspiration especially in a patient with a known history of dysphagia related to a cerebrovascular accident. Given the risk of polymicrobial infection, it is reasonable to follow a step down approach with broad initial antiobiotic coverage until a more specific organism is identified. If a patient has a known history of MRSA (methicillin resistant Staph aureus), then vancomycin or linezolid could be used initially until MRSA is excluded as the offending organism. Community acquired pneumonia can be managed with beta lactam with beta lactamase inhibitors or cephalosporin (ceftriaxone or cefotaxime) with or without a macrolide. In the outpatient setting, long term care residents or those with severe COPD (FEV1 <30%) present the greatest risk of drug resistant S. pneumonia. They benefit from fluoroquinolones such as levofloxacin, sparfloxacin, or moxifloxacin.

Duration of therapy can vary from 2 weeks in complicated hospital acquired pneumonia (as a result of Pseudomonas or Stenotrophomonas) versus 8 days in a less complicated pneumonia.

• Prevention

The elderly benefit from immunization, smoking cessation, skin testing with purified protein derivative for tuberculosis, and aggressive treatment of comorbidities including decreasing aspiration risk in post stroke setting and limiting sedative hypnotics. 

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VI. INFLUENZA

• Epidemiology
  This disease accounts for 40,000 deaths annually with the majority of deaths in older adults. 
  
  
• Clinical Presentation
  Influenza typically presents in late October with potential to persist until March. Influenza can lead to a multitude of symptoms which need to be differentiated from other more benign conditions such as the common cold. Of note, influenza will present with more severe systemic symptoms as described by the affected – “feels like a Mack truck hit me”.  The two conditions are described in the chart below.

Symptom	Influenza	Common cold
Onset	Abrupt	Gradual
Fever	99.4 to 104F  (37– 40 C)	Increase < 1 degree F
Myalgia	Severe, common	Uncommon
Arthralgia	Severe, common	Uncommon
Anorexia	Common	Uncommon
Headache	Severe, common	Mild, common
Cough (dry)	Common, severe	Mild-moderate
Malaise	Severe	Mild
Fatigue	Common lasts 2-3 wks	Mild, short-lasting
Chest discomfort	Common, severe	Mild-moderate
Stuffy nose	Occasional	Common
Sneezing	Occasional	Common
Sore throat	Occasional	Common

• Diagnosis
  • Nasopharyngeal swabs can be useful with rapid antigenic tests demonstrating 80-90% sensitivity and specificity. The tests can assist in differentiating influenza from Respiratory Syncitial Virus (RSV).
  • RSV can cause repeated infections throughout life as a result of incomplete immunity to the virus.  Predominant presentation can be moderate-to-severe cold-like symptoms, but there is risk of severe lower respiratory tract disease. 
  • RSV infection is an important illness in elderly, with a disease burden similar to that of nonpandemic influenza A in a population in which the prevalence of vaccination for influenza is high. An effective RSV vaccine may offer benefits for these adults. (9)
    
    
• Therapy

All therapies for influenza are most effective if initiated within 24-48 hours of symptom onset. If patients present after 72 hours, supportive therapy is indicated.

M2 inhibitors (amantadine and rimantadine) are effective against influenza A.  Amantadine requires renal dosing and presents an increased risk of severe adverse effects such as blurred vision, confusion, difficulty urinating,hallucinations and swelling of extremities.

Neuraminidase inhibitors (zanamivir and oseltamivir) can be used for both influenza A and B.  Oseltamivir is preferred for the elderly due to its capsule form; zanamivir is more difficult as an inhaler.

• Prevention

Amantadine, rimantadine, zanamivir, and oseltamivir can all be used for prevention in outbreaks within a long term care facility in combination with the vaccine.  These medications have the potential for a 90% reduction in severe illness, but amantadine is typically avoided in the elderly as a result of the side effects.

The influenza vaccine has a maximum of 80% efficacy in preventing severe disease, hospitalization, and death in the elderly.  It takes up to 2 weeks for one to produce an effective antibody titer. 

There are two types of influenza vaccine: 

• The first one is a trivalent inactivated influenza vaccine (TIV) which is indicated for those who are not candidates for the live vaccine; live vaccine is contraindicated for children less than age 5, pregnant women and immunocompromised patients. 
• The second form is a live attenuated influenza vaccine.  This form is indicated for healthy, nonpregnant persons aged 5--49 years who want to avoid influenza, and those who might be in close contact with persons at high risk for severe complications, including health-care workers.  This form is useful especially if there is not any contraindications and a limited amount of the TIV.
  
  
  • Indications for flu vaccine (mainly the trivalent inactivated vaccine)
    • Over the age of 65
    • Under the age of 65 and chronic illnesses such as diabetes mellitus, congestive heart failure, COPD, end-stage renal disease, immunocompromised patients, HIV patients, cancer patients
    • Workers in long-term care facilities, nursing homes, hospitals and all medical caregivers with the benefit of herd immunity to protect the residents or patients

Suggested reference: www.cdc.gov (“Influenza” section)

Good hygiene is imperative; soap and water hand washing and alcohol gel wash are both effective.  Masks can prevent airborne transmission with use of masks for those actively coughing.  Droplet and contact isolation are needed for influenza and RSV.  It is notable that influenza virus is viable for 2-8 hours on inanimate objects and is spread by respiratory droplets. 

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VII. URINARY TRACT INFECTIONS

• Epidemiology

This is the most common clinical illness in those over the age of 65 with an incidence of 10.9 per 100 person years in men and 14 per 100 person years in women.

Causative organisms are similar to those in young adults with gram negative bacilli (such as Escherichia coli), but the elderly have an increased risk of the resistant organisms such as in Pseudomonas aeuginosa or gram positive organisms (enterococci, coagulase negative staphylococci, and Streptococcus agalactiae.  Those with indwelling catheters present with S. aureus or fungi (Candida spp.). 

• Clinical Presentations of Urinary tract infections (UTIs)
  • Asymptomatic Bacteruria

  The etiology of the diagnosis occurs with the collection of urine samples as result of a subtle change in function in the elderly without fever, dysuria, or other typical clinical features (refer to prior table on the  minimum criteria for use of antibiotics)

  This condition will present more commonly in the following settings: nursing home female residents, in the setting of all males with condom catheters, or in the setting of a long term foley catheters for both men and women.

  Management is accomplished by observing the patient rather than initiating antibiotics.

  • Cystitis
    • Clinical presentation
      This is a lower urinary tract infection presenting with dysuria, frequency, and urgency.  Note there is frequent absence of fever.
      
      
  • Treatment
    There is an effective response to 3 days of antibiotic therapy in both young and older women.  A urine culture is not mandatory unless one fails first line therapy. 

    The antibiotic options include fluoroquinolones, amoxicillin
    (especially enterococci) and first generation cephalosporins.   E. coli has shown 10-20% drug resistance to trimethoprim-sulfamethoxazole (TMP-SMX)

  • Lower and Upper UTIs in elderly men
    • Risk factors
      Elderly men frequently have prostatic hyperplasia and autonomic neuropathy (as in diabetes mellitus) which increases the risk of incomplete bladder emptying.  The prostate can act as a reservoir of infection, thus it is beneficial to obtain urine cultures for men.
    • Treatment and Management
      Antibiotics should be administered for minimum of 14 days with the duration of therapy being longer in men as compared to women.  If the prostate is involved, then a 6 week course should be applied.  The choice of antibiotics is similar to women with use of fluoroquinolones or TMP-SMX

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VIII. GASTROINTESTINAL INFECTIONS

• Clostridium Difficile Colitis
  • This form of infection occurs after antibiotic administration which alters colonic mucosal flora to result in diarrhea.  In particular, fluoroquinolones, clindamycin, ampicillin, amoxicillin and the cephalosporins are common culprits. 
    
    
  • The organism has been identified as a gram-positive spore-forming anaerobic bacillus.  There are different strains producing toxins, but toxin A is the most common cause of infection.
    
    
  • Clinical presentation can be variable with fever, cramping, nausea, fatigue or diarrhea.  The diarrhea ranges from minimal to profuse watery forms, often with a characteristic odor.  A direct exam per colonoscopy can demonstrate yellow adherent plaques scattered over hyperemic mucosa, but the colitis may be limited to the proximal colon and missed on a flexible sigmoidoscope.  A colonoscopy is not required for diagnosis as toxin A or B is able to be identified from a stool sample.  (see images: Clostridium Difficile Colitis and Pseudomembranous colitis CT)
    
    
  • Therapy of Clostridium difficile colitis begins with oral metronidazole. Oral vancomycin may be indicated if there is resistance to metronidazole after two complete courses. Contact isolation is needed, and it is important to note that foam based hand cleansers are not effective at killing the spores so strict hand washing should be observed.

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IX. INFECTIVE ENDOCARDITIS

• Infective endocarditisis (IE) has become more common in the elderly as prosthetic cardiac valves become more prevalent.  The different types of IE are native or prosthetic valve endocarditis that can be separated into acute or subacute.  Potential organisms depend on the timing of the infection and additional risk factors. (see chart- below).
  
  
• The clinical presentation includes fever, new or changing heart murmur, evidence of systemic emboli (Janeway lesions or Roth spots) in the setting of positive blood cultures and findings of a vegetation on a cardiac valve as diagnosed per echocardiogram.  Acute endocarditis presents rapidly with a high spiking fever (typically greater than 104 degrees Farenheit), systemic embolic findings, and more severe illness with high mortality risk. Subacute endocarditis presents in a more indolent manner with low grade fever (less than 103 degrees F) and slow destruction of cardiac structures.   (see pictures: Janeway Lesions, Osler nodes)
  
  
• Diagnosis is based on specific criteria and diagnostic steps.  The organism can be identified based on a positive blood culture or by histology from a vegetation.  The formal diagnostic criteria applies major and minor criteria otherwise known as the Duke criteria.  (see chart)

Acute	Subacute	Prosthetic Valve – Early (less than 2 months after surgery)	Prosthetic Valve – Late ( greater than 2 months after surgery)
1. Staph. aureus	Viridans strep. Enterococci Gram positive bacteria Gram negative bacteria Yeast Fungi	Coagulase negative Staph. Coagulase positive Staph. Gram negative bacteria Fungi	Streptococci Coagulase negative Staphylococci

Diagnostic Criteria

2 major criteria OR 1 major and 3 minor criteria OR 5 minor criteria

Major Criteria	Minor Criteria
Positive blood cultures for IE	Predisposition  condition – heart condition or intravenous drug use
Typical microorganism for infective endocarditis from two separate blood cultures Viridans streptococci Streptococcus bovis HACEK group (Haemophilus, Actinobacillus, actinomycete, Cardiobacterium hominis, Eikenella, Kingella kingae Staphylococcus aureus Community acquired enterococci	Vascular phenomena Major arterial emboli Septic pulmonary infarcts Mycotic aneurysm Intracranial hemorrhage Conjunctival hemorrhages Janeway lesions
Persistently positive blood culture, defined as recovery of a microorganism consistent with IE from: Blood cultures drawn more than 12 hours apart OR All of three or a majority of four or more separate blood cultures, with first and last drawn at least one hour apart Single positive blood culture for Coxiella burnetii	Immunologic phenomena Glomerulonephritis Osler’s nodes Roth spots Positive rheumatoid factor
	Fever of 38.0 Degrees Celsius (100.4 degrees F)
	Microbiological evidence Positive blood culture (but not per major criteria) Serologic evidence of active infection with organism consistent with IE

• Echocardiogram findings can include the following:
  • An oscillating intracardiac mass either on a valve or surrounding structures or in the path of regurgitant jets, or on implanted material (such as a prosthetic valve) without alternative anatomic explanation (See “mitral valve vegetation” on a native valve)
  • Abscess
  • New partial dehiscence of prosthetic valve
  • New valvular regurgitation
  • Increase in or change in preexisting murmur
    
    
• Management includes intravenous antibiotics based on the specific organism found, typically for 4-6 weeks.   Surgery may be indicated if there is not response to antibiotics after 7-10 days.  Poor response is shown by persistent fevers, continuing systemic emboli or persistent positive blood cultures.  Also it is best to consider surgery if there evidence of valvular regurgitation with acute heart failure after placement of prosthetic valve (especially if it is the aortic valve). 

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X. TUBERCULOSIS

• Epidemiology

In the United States, 16 million people are infected with Mycobacterium tuberculosis; 25% of this population are over the age of 65 and the majority of these patients are in the long term care setting. 

• Clinical presentation

Typically, patients present with progressive weight loss, night sweats, chronic cough and / or blood streaked sputum.

More atypical features are generalized fatigue, anorexia, decreased functional status, or low grade fever.  The infiltrate may be basilar on the chest x-ray as an atypical feature. The elderly are more likely to have extrapulmonary infections including miliary (disseminated) disease, meningitis, osteomyelitis, or urogenital disease. The active cases can be either a reactivation of the disease or primary infection.

(Radiographic Images: Normal X-ray, Miliary TB X-ray, and Primary Tuberculosis x-ray)

• Diagnosis

Specimens can be obtained from the sputum, urine or other specimen as indicated by the presentation with the use of DNA probes to demonstrate a positive culture within 24 hours. 

• Purified protein derivative (PPD) skin tests

The administration of a PPD requires interpretation within 48-72 hours of placement, but there remains confusion in diagnosing Mycobacterium tuberculosis (MTB) with the PPD skin test.  Refer to the chart below for interpretation of PPD results.

Two step testing is applied in the long term care facilities due to the potential for delayed immune response in previous PPD converters.  This procedure is accomplished by retesting in 2 weeks for those with <10 mm of induration.  If the second skin test is >/= 10 mm of induration or the second test is 6 mm or greater as compared to the first test, then the second test is a positive PPD.  Note this group is not considered new PPD converters.

>/= 5 mm	>/= 10 mm	>/= 15 mm
HIV infected Chest x-ray positive for MTB (fibrotic changes) History of close contact with persons diagnosed with active MTB Immunosuppression (organ transplant history or chronic corticosteroid use defined as greater than 1 month of prednisone 15 mg per day)	Nursing home residents, prisoners, or other members of residential care facilities Recent converters (hx of PPD<5 mm) Recent immigrants (within the past 5 years) with endemic MTB Injection drug users Homeless and residents of homeless shelters Comorbid risk factors of gastrectomy, jejunoileal bypass, >10% below ideal body weight,  chronic kidney disease, diabetes mellitus, silicosis, leukemia, lymphoma, or other carcinomas (head, neck, or lung) Children < age 4, infants, children, or adolescents exposed to adults in high risk categories (as noted above)	All other groups

Suggested Reference: American Thoracic Society’s statement on Diagnostic Standards and Classification of Tuberculosis in Adults and Children. http://www.thoracic.org/sections/publications/statements/resources/tbadult1-20.pdf

• Treatment for Active Mycobacterium tuberculosis

Four drug therapy approach is indicated for active MTB which includes isoniazid (
INH), rifampin, pyrazinamide and ethambutol or streptomycin.  The most common regimen is INH, rifampin, and pyrazinamide for 2 months, then taper down to INH and rifampin for additional 4 months.

• Prophylaxis

Indicated for asymptomatic person with positive PPD if recent converter or if in a high risk group.  The prophylaxis approach uses INH for 9 months, and pyridoxine (to prevent peripheral neuropathy while on INH).

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XI. HERPES ZOSTER

• Mechanism of infection is a result of reactivation of varicella virus in dorsal root ganglia with episodes of stress or illness which decreases an individual’s resistance.  In addition, the elderly have altered physiology with immune senescence.
  
  
• Transmission can occur by direct contact with active shingles and blister fluid to someone who has never had varicella or chickenpox.  Herpes zoster is not airborne.  If the lesion is crusted, then they are not contagious.  An individual is not infectious prior to onset of the blisters or after the lesions have healed, even if they have post-herpetic neuralgia.
  
  
• Clinical presentation could initially be patches of erythema with associated pain along a unilateral dermatome.  Later, there is progression to grouped vesicles in a dermatomal pattern usually on the face or trunk.  The clinical course is the progression from vesicles to pustules to crusting in 7-10 days from the onset of the vesicles. (see images:  herpes zoster, herpetic vesicles and herpetic opthalmicus)
  
  
• Diagnosis can be confirmed by Tzanck test with lesion scrapings demonstrating giant cells, but typically the diagnosis is made by clinical exam findings and history.
  
  
• Treatment needs to be initiated within 72 hours from the onset of the rash.  The treatment options include famciclovir 500 mg or valacyclovir 1 gram three times a day or acyclovir 800 mg five times a day with total therapy duration of 7 days.  The benefit of therapy is the potential to reduce duration of eruption to 1-2 days and to reduce the acute neuropathic pain of post-herpetic neuralgia to less than one month.
  
  
• Vaccination against herpes zoster has been developed.  Zostavax was licensed by the Food and Drug Administration on May 25, 2006 for the prevention of shingles or herpes zoster infection in those over the age of 60.  This vaccine does not treat shingles, and it does not treat post-herpetic neuralgia after either condition has developed.  This vaccine is covered by Medicare Part D, but it is not covered by Medicare Part B (as are the influenza and pneumococcal vaccines).

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XII. MISCELLANEOUS

• Osteomyelitis
  • The most common source is Staphylococcus aureus The individual risk factors for osteomyelitis include non-healing or slow to heal pressure ulcers or diabetic foot infections.
    
    
  • Diagnosis can be completed using blood cultures or wound cultures for specific microbiologic identification.  The cultures are used due to increased frequency of gastrointestinal & genitourinary flora causing osteomyelitis more frequently in the elderly as compared to younger adults.   However, routine surface swab cultures of pressure ulcers may not always be helpful due to the risk of contamination.
    
    
  • Radiographic images can be used to support the diagnosis of osteomyelitis.  Initially, a plain film x-ray is appropriate.  If a difficult diagnosis, an MRI can be done and occasionally, a nuclear medicine Technetium-99 study may be helpful to indicate areas of bone inflammation or infection. (see images: “foot osteomyelitis” and “nuclear medicine osteomyelitis”)
    
    
  • General management should include intravenous antibiotics.  Aggressive antimicrobial therapy is directed toward mixed aerobic and anaerobic bacteria. 
    
    
  • In efforts to prevent progression of a nonhealing ulcer to osteomyelitis or to prevent potential need for amputation in the setting of existing osteomyelitis, then surgery is used to aggressively debride the wound.  Amputation is frequently necessary to salvage the unaffected portion of the limb.
• HIV
  • In the United States, epidemiology demonstrates that 10% of all newly diagnosed AIDS (acquired immunodeficiency syndrome) patients are over the age of 65. The primary mode of transmission is heterosexual activity, and there is lack of sexual education among the elderly.  In particular, the elderly lack the regular use of condoms.
    
    
  • Diagnosis of HIV in the elderly supports another atypical presentation.  Forgetfulness, lack of appetite and weight loss can be symptoms of HIV infection.  They may also have clinical findings of dementia, recurrent pneumonia and bilateral peripheral neuropathy (paresthesias). The altered T cell response in the elderly places them at risk of rapid progression to AIDS if untreated.
    
    
  • Therapy can be successful with the elderly having similar response to HAART (highly active antiretroviral therapy) and similar treatment response of opportunistic infections as compared to younger adults.   Side effects of HAART can be accelerated atherosclerosis and glucose intolerance, so aggressive prevention of these conditions is required.

  HIV is probably the most treatable infectious cause of dementia and much more likely to reverse with therapy than syphilis.

• Neurosyphilis
  • An atypical presentation of this condition should be considered in the setting of stroke or dementia especially in someone younger than 65 years old.  Additional atypical features could include unilateral deafness, altered gait, uveitis, and optic neuritis.  (see image: “uveitis”)
    
    
  • Diagnosis can be completed by use of cerebrospinal fluid (CSF) to demonstrate elevated total protein, lymphocytic pleocytosis and positive CSF VDRL which is 75% sensitive.
    
    
  • Treatment uses aqueous penicillin G.  All forms of treatment for neurosyphilis last for 10-14 days.  If penicillin allergy, the alternatives could be doxycycline 100 mg twice a day for 28 days if syphilis present for more than one year duration or if duration is unknown. 
    
    
  • Follow up of neurosyphilis requires repeat lumbar punctures every six months to follow cerebrospinal fluid cell count.

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XIII. FEVER OF UNKNOWN ORIGIN

• Epidemiology
  • In the elderly, it is possible to determine the cause of the FUO in over 90% of the cases; 33% of the cases are a treatable infection.  When comparing the elderly to younger population, treatable infections have similar incidence rates including intra-abdominal abscesses, bacterial endocarditis, tuberculosis or osteomyelitis. 
  • In contrast to the young, there is a more common occurrence of collagen vascular diseases in the elderly including giant cell arteritis, polymyalgia rheumatica and polyarteritis nodosa.  Two other etiologies of FUO in the elderly are malignancies (i.e., lymphoma and leukemia) and medications.
• Diagnosis
  • It is defined as a temperature greater than 101 degrees F for 3 weeks, and it must persist without a diagnosis after 1 week inpatient evaluation for the etiology. 
  • The comprehensive evaluation should be initiated with a detailed history to review the patient’s travel history, medications (antibiotics, corticosteroids, or chemotherapeutic agents), recent procedures or surgeries.  In addition, one should discuss any potential for past exposure to tuberculosis, HIV or any other potential for immunosuppression.
  • After the history has been discussed and an all inclusive physical examination has been completed, then the evaluation should be expanded to laboratory testing.  The initial labs should include complete blood cell count with differential, hepatic transaminases, sedimentation rate and three different sets of blood cultures from 3 different sites.  According to the individual’s history, then the following should be done:  PPD skin test, thyroid stimulating hormone, antinuclear antibody, antinuclear cytoplasmic antibody, or human immunodeficiency virus.
  • If there is still no obvious source, then it is beneficial to proceed to imaging or biopsy as indicated by prior findings.  Thus, a CT scan of the chest or abdomen or pelvis could be used to assess for lymphadenopathy or an occult mass or abscess.  If temporal arteritis is suspected, then a temporal artery biopsy could be helpful.  If the labs indicated, then a bone marrow or liver biopsy could be completed.
  • If above studies are non diagnostic, then alternate approaches could include an Indium-111 labeled WBC or a Gallium-67 scan and/or a surgical approach per laparoscopy or exploratory laparotomy.
  • If this extensive evaluation does not lead to an appropriate diagnosis, then an empiric medication trial may applicable.  This empiric trial is reserved for antituberculosis therapy in rapidly declining host or high suspicion for tuberculosis.

  Fever of unknown origin has been categorized based on specific sources of acquiring the infection and associated comorbid conditions.  (see attached chart)

• Treatment

The goal is to determine the underlying illness which then can be treated accordingly.  Otherwise, it is recommended to delay empiric treatment of a fever to avoid altered clinical picture from the antibiotic therapy unless the patient is in imminent risk of dying.

Category	Fever Definition	Medical Evaluation	Duration of Fever	Sources of Condition
Classic	Temp > 38.3 Celsius	Minimum of 3 outpatient visits or 3 inpatient days	Greater than 3 weeks	Infection, malignancy, collagen vascular disease
Nosocomial	Temp > 38.3 Celsius	Evaluation of 3 inpatient days	Hospitalized greater than 24 hours but  without fever on admission	Clostridium difficile enterocolitis, medication induced, pulmonary embolism, septic thrombophlebitis, sinusitis
Immune deficient	Temp > 38.3 Celsius	Evaluation of at least 3 days with hx of neutrophil count <500 per mm^3		Opportunistic bacterial infections, aspergillosis, candidiasis, herpes virus
HIV-associated	Temp>38.3 Celsius		Greater than 4 weeks for outpatients versus >3 days for inpatients	Cytomegalovirus, Mycobacterium avium-intracellulare complex, Pneumocystis carinii pneumonia, medication induced, Kaposi’s sarcoma, lymphoma

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XIV. REFERENCES

1. Pompei P, Murphy JB, eds. Geriatric Review Syllabus:  A Core Curriculum in Geriatric Medicine.  6th ed.  New York:  American Geriatrics Society; 2006.
2. Mouton, C; Bazaldua, OV; Common Infections in Older Adults.  American Family Physician. 2001; 63(2):  257-267.
3. Castle SC, Yeh M, Toledo S, et al.  Lowering the temperature criterion improves detection of infections in nursing home residents.  Agign Immunol Infect Dis. 1993;4(2):  67-76. 
4. Roth, AR; Basello, GM; Approach to the Adult Patient with Fever of Unknown Origin.  American Family Physician.  2003;  68(11): 2223-2228
5. Loeb M, et al. Development of minimum criteria for initiation of antibiotics in residents of long term care facilities:  results of a consensus conference.   Infect Control Hosp Epidemiol.  2001;22:120-124.)
6. Ely EW, Angus DC. Williams, MD, et al. Drotrecogin alfa (activated) treatment of older patients with severe sepsis.  Clin Inf Dis.  2003;37 (2):187-195.
7. Fine MJ, Smith DN, Singer DE.  Hospitalization decision in patients with community acquired pneumonia:  a prospective cohort study.  Am J Med 1990; 89:713-21. 
8. Fine MJ, Auble TE, Yealy DM, et al.  A prediction rule to identify low risk patients with community acquired pneumonia.   N Engl J Med 1997;336: 243-50.
9. Falsey, AR, Hennessey PA, et al.  Respiratory syncytial virus infection in elderly and high-risk adults.  N Engl J Med. 2005 Apr 28;352(17):1749-59.

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Case Study #1

Mr. A is a 85 year old Caucasian male who has been a long term care resident for the past 6 months due to his Dementia of Alzheimer’s Type (DAT).  Normally, he is a pleasant and appropriate resident who only requires moderate assistance with his ADLs and management of his longstanding antihypertensive medications, including atenolol and lisinopril.  In the past 3-4 days, he has been difficult to manage with refusal of his medications and eating as reported by the nursing staff.  He has become aggressive, and he is hitting other residents.

His past medical history includes hypertension (baseline blood pressure of 130’s/80’s), DAT, mild prostatic hypertrophy (with a history of a normal prostate serum antigen; digital rectal exams in the past have only demonstrated mild enlargement of the prostate without nodules).  He has not been hospitalized in the past year and he has not had any medication changes recently.  His medications are noted previously with the addition of daily aspirin and multivitamin. 

At this time, what additional information would be helpful in your evaluation of this patient?

Review of systems:  Temp – 100.8 degrees F (baseline temp of 97.0 degrees F), poor appetite, behavior changes, one episode of new urinary incontinence. He has no diarrhea, nausea, vomiting, dyspnea, cough, and an otherwise negative ROS.

Exam: Temp.- 100.8 F  R – 22  P – 100   BP- 100/72 

Pertinent positives on exam: Less energetic than usual, follows commands, dry mucus membranes, tachycardic with regular cardiac rhythm, clear lung fields, abdomen soft without masses, positive costovertebral angle tenderness, dry skin without rash, extremities without edema, prostate tender with mild bogginess and no nodules.

A UA with micro is obtained and shows positive leukocyte esterase, nitrites, moderate amount of bacteria, and greater than 50 WBC per HPF.  Thus, the urine sample is sent for culture with sensitivities.   He also has a basic metabolic panel with normal electrolytes but he has a mildly elevated creatinine from his baseline of 1.1 to 1.8 now.  Finally, a prostate serum antigen was elevated at 5 (from baseline of 1.5).  At this time, his antihypertensive medications are held and supportive measures are provided including oral hydration.  In addition, he is empirically treated with ciprofloxacin (renal dosed). 

Questions

1. What is your diagnosis at this time?
2. How would you like to manage and treat Mr. A?

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Case Study #2

Mrs. P is an 82 year old female residing in the assisted living facility.  Her family brought her to the emergency department due to a vague report of her mental status changing with her report of general malaise and body aches.  In further review, she describes more severe symptoms of body and joint aches with associated sharp headache and dry cough.  She denies recent travel or known ill contacts in the facility.  After much questioning, she reports that her great grandchildren did visit her about one week ago to show her their Halloween costumes. 

Her past medical and surgical history includes osteoporosis, controlled hypertension,   hyperlipidemia, osteoarthritis, and a history of cholecystectomy, hysterectomy, and appendectomy.  Her current medications are alendronate, hydrochlorothiazide, simvastatin, aspirin, and acetaminophen as needed for joint pain.   Her social history is significant for lifelong nonsmoker status, one glass of wine per month, and no other herbal, over the counter medications or alternative substances.  Prior to the hospitalization, she was independent in her activities of daily living with minimal assistance needed for reminders to take her medications.

Review of systems (as per above)

On exam:

Temp 102 degrees F  P– 110  R 28  BP – 95/52  SaO2 – 87% on room air

Gen: Fatigued appearance, answers questions and follows commands fully, small statured 82 year old Caucasian female with difficulty staying awake on exam.

HEENT:  NCAT, PERRLA, OP –dry membranes, hyperemia of the posterior pharynx, no exudate/tonsillar enlargement

Neck:  supple, no cervical lymphadenopathy;  CV:  tachycardia with regular rhythm

Lungs:  coarse diffusely with mild expiratory wheeze;  Abd:  benign 

Extremities: nontender to touch diffusely, good range of motion without joint effusions, no edema

Skin: no rash, but flushed and warm to touch diffusely

Labs: basic metabolic panel normal, normal creatine kinase of 46, but a complete blood cell count showed an elevated white blood cell count of 18,000 with predominant lymphocytes on differential with stable hemoglobin of 11.  An arterial blood gas showed a PaO2 of 55 mmHg and PaCO2 of 40 mmHg. 

Chest x-ray showed diffuse interstitial infiltrates.

Questions

1. At this time, how would you help Mrs. P?  What additional information would be helpful to assist your diagnosis of her illness?
2. What is this lab?
3. How would you adjust your management of Mrs. P at this time?

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Case Study #3

Mrs. K is a 68 year old Caucasian female who presents as an inpatient for her routine colonoscopy in follow up of her known history of ulcerative colitis.  In the past year, she has been well controlled on azathioprine with a history of failed response to maintenance therapy using mesalamine and past intermittent steroid therapy due to frequent relapses. 

In obtaining her complete history, she relates ulcerative colitis without evidence of malignant changes on prior colonoscopies.  Her other medical conditions include treated dyslipidemia with omega-3 without need for additional medications.  Otherwise, she only takes a baby aspirin daily, multivitamin, calcium with vitamin D.  She has been very dedicated in her annual physical exams with routine mammograms, one normal bone mineral density test, annual flu vaccines, a pneumococcal vaccination since age 65, and biannual normal dental cleanings.  She denies a life long history of tobacco use, alcohol use, or illicit drug use.

In reviewing her organ systems, she reports fairly stable weight with possible 6 pound weight loss in the 6 months.  Then, she admitted to recurrent elevated body temperatures over the past 2 weeks without additional symptoms.  And otherwise, she has a negative review of systems.

On exam:

Temp 102 (baseline 97.0 degrees F),  P – 99,  R – 24,  BP – 100/70,  SaO2 – 93% on Room Air

Pertinent exam findings include

Gen:  No acute distress, Small statured CF who appears her stated age, Alert, Oriented x 3

Lungs: Occasional cough on exam, otherwise clear lung exam

Fingernails with mild clubbing

Otherwise negative exam

Questions

1. At this time, what would you like to do for further evaluation and management of her fever?
2. Now how would you like to manage this patient?

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