Michael J. Koronkowski, Pharm.D.
Spring 1998

Infectious Disease and Host Resistance in Older Persons

  1. Introduction to Infectious Disease in the Elderly
  2. Pharmacokinetics of Antibiotics in the Elderly
  3. Alterations in Host Resistance
  4. Bacterial Pneumonia
  5. Urinary Tract Infections (UTI's)
  6. Herpes Zoster or "Shingles"
  7. Case 1
  8. Case 2

Assigned Readings:

  1. Handout materials.

Suggested Readings:

  1. Yoshikawa TT. The cost of inappropriate use of anti-infective agents in older patients. Drugs & Aging 1995;6(4):263-7.
  2. Yoshikawa TT, Norman DC. Treatment of infections in elderly patients. Med Clin North Am 1995;79(3):651-61.
  3. Yost RL. Infectious Diseases. Pgs. 176-184.In eds. Delafuente JC, Stewart RB. Therapeutics in the Elderly. Williams and Wilkens, Baltimore, Maryland 1988.

Learning objectives:

  1. Identify the age associated alterations in host resistance as they relate to specific systems.
  2. Given a case, be able to identify the patient’s risk factor for infection as they relate to learning objective #1, the patient’s environment, and co-morbid conditions.
  3. Compare the different patterns of infecting organisms based upon the setting in which the patient resides or where the infection was acquired.
  4. Identify patients whose antibiotic selection and/or dosing may need to be adjusted based upon clinical findings, disease state an presentation, and history.
  5. List situations where the pneumococcal or influenza vaccine is indicated.
  6. Identify situations where amantadine prophylaxis is warranted, including how the it should be dosed, duration of treatment, risk for adverse effects and adverse effects.

I. Introduction to Infectious Disease in the Elderly

A. Epidemiology

Infections rank as the second leading cause of death in persons 65 years. Only deaths from cardiovascular disease rank higher. Among the individual causes of death, pneumonia an influenza rank 6th, 5th and 4th for persons 65-74, 75-84, and 85+, respectively. The mean age of patients diagnosed with infective endocarditis is -55 years and more than 50% of cases are in persons >60 years. Forty percent of bacteremia/sepsis occur in the older adult and is responsible for 60% of deaths in this population. Tuberculosis is disproportionately prevalent in older persons for two reasons 1) reactivation of old cavitation disease and 2) its spread in nursing homes from residents with reactivated old disease to residents without prior exposure. Several other common infectious processes include UTI’s, intra-abdominal, and soft-tissue infections. Sixty percent of all cases of tetanus in the U.S. occur in older adults. Tetanus is a common cause of infection in the nursing home due to poor booster programs and the great prevalence of soft-tissue wounds/infection. Finally, one cannot overlook the oral cavity as a source of infection in this population.

B. Altered Clinical Presentation

1. Classic symptoms such as fever, elevated white blood cell count (WBCs), or productive cough may be absent.

2. Subtle symptoms - loss of appetite, confusion, delirium, weight loss, or weakness may be the earliest or only symptom of an infection.

II. Pharmacokinetics of Antibiotics in the Elderly

A. Absorption (examples of alterations)

Delayed Absorption

No Change

Increased Variability

Sulfisoxazole Penicillin V Ampicillin
  Cephalexin Sulfamethoxazole
  Tetracycline Ciprofloxacin
  Metronidazole  

Interactions affecting absorption

B. Distribution

Volume of Distribution (Vd)

Increased Vd

No Change

Decreased Vd

Vancomycin Ampicillin Metronidazole
Cephalothin Aminoglycosides  
Cefoxitin Isoniazid  
  Rifampin  
  Aztreonam  

Protein Binding

Reduced

No Change

Cefoxitin Penicillin
Ceftriaxone Aztreonam
  Sulfadiazine
  Vancomycin

C. Clearance

Reduced

No Change

Aminoglycosides Aztreonam
Most Penicillins Isoniazid
Most Cephalosporins Rifampin
Most Quinolones  
Vancomycin  
Metronidazole  

NOTE: The significance of these changes is discussed in the assigned reading. The elderly are a very heterogeneous group an it is just as easy to under dose someone as it is to overdose them.

III. Alterations in Host Resistance

A. Age-related Reduction in Inflammatory and Immune Response (A state of immune dysregulation )

All changes are believed to be related to the involution of the thymus and a decrease in the functional activity of T-lymphocytes.

1. Nonspecific responses in older persons

a . Polymorphonuclear neutrophils (PMN’s, segs and bands)

* decreased chemotaxis

* decreased intracellular killing

* particle ingestion unchanged

* decreased colony-stimulating factor older

persons with and without chronic disease compared to younger persons.

b. Macrophage - no consistent changes have been identified.

2. Humoral Immunity - decreases with age

a. Peak response (in terms of antibody production) occurs in childhood, by age 50 a 50% decrease in response and age 75 a 90% decrease in response has been reported. Examples include the diminished antibody response by older persons after pneumococcal and influenza vaccination.

3. Cell-Mediated Immunity

Delayed hypersensitivity reactions are decrease after age 60. An important example is the purified protein derivative skin test (PPD) for tuberculosis for which a decrease or false negative response is common after the age of 70 (the population at greatest risk for reactivation). The lack of response, even when an anergy battery is positive, may be due to immunosenescense and the reapplication of a second 5U ppd -2 week later a booster) is indicated.

4. Fever is usually triggered by a microbial agent or an antigen which either directly or indirectly stimulates the phagocytes in the bone narrow to produce endogenous pyrogen (interleukin 1) which then stimulates the anterior hypothalamus to elevate the bcdy's temperature "set point". In order to achieve the new set point vasoconstriction and shivering occur as well as a behavioral response to seek a warm environment. It is the purpose of fever to inhibit microbial growth and enhance immune function. Therefore, some specialists in geriatric infectious disease do not always advocate treating fever providing adequate hydration, neurologic and nutritional status can be maintained.

Most older persons are capable of generating a febrile response in the face of infection and this usually signifies a serious infection. However, it not uncommon for the older patients to remain afebrile or have a blunted febrile response. Such cases are associated with a poor prognosis because the delay in diagnosis. One series of 187 cases of pneumococcal bacteremia found that 29% of older patients were afebrile.

The reason why some older patients remain afebrile or have a blunted febrile response is unclear. Several hypotheses have been suggested 1) thermal homeostasis is disturbed, 2) changes in endogenous pyrogen, 3) a decreased response by the hypothalamus to endogenous pyrogen and 4) an inability to conserve and maintain body heat. In any case, a temperature of 100' in an elderly patient (without a known source) warrants a comprehensive work-up for a infection.

B. Age-related Changes in Organ Structure and Function

1. Skin

As we age the skin becomes thinner and less hydrated. These changes reduce its effectiveness as a barrier to infection and make it less resistant to shearing forces and subsequent tearing.

2. Respiratory Tract

As a result of the loss of elastic tissue and tone an increased chest diameter and weakened musculature, lower airways collapse, the ability to cough up secretions decreases, and colonization of the tracheobronchial tree results. In addition, mucocilliary transport of secretions and foreign material is decreased.

3. G.I. Tract

  1. Saliva production can decrease with aging or as a result of therapies. Saliva contains antibacterial properties and buffers that maintain the pH of the oral cavity.
  2. A slowing or decrease in esophageal motility may increase the risk of aspiration.
  3. Achlorhydria has been associated with infection secondary to E. coli and the reactivation of tuberculosis.

4. Urinary Tract

Any condition (not necessarily aging) resulting in urine retention in the bladder can lead to chronic bacteriuria. This does not signify an infection unless symptoms or pyuria coexist. Examples include a neurogenic bladder, an obstruction, or an indwelling catheter. In addition, the associated decline in renal function reduces ones ability to acidify the urine, maintain its high osmolality, and excrete a high urea and organic acid load. The normal homeostasis of these functions are defense mechanism against infection in the urinary tract. It has also been shown that the concentration of Tamm-Horsfall protein is lower in older persons. This protein is believed to inhibit the adherence an colonization of gram negative bacteria to the bladder.

C. Diseases That Compromise Host Defense

1. atherosclerosis 5. osteoporosis
2. diabetes mellitus 6. dementia
3. COPD 7. diverticulosis
4. neoplasms 8. constipation

D. Environmental Factors

1. More frequent admissions, increased length of stay

2. Increased drug use (particularly those that affect the immune system)

IV. Bacterial Pneumonia

A. Predisposing Factors to Severe Infection

1. increased virulence of the respiratory pathogens

2. inability of the hosts defense to confine the infection

3. delay in recognition and treatment

4. decreased pulmonary reserve

5. number and severity of other preexisting illnesses

B. Clinical manifestations in Young vs.Older Adults

Manifestation Young Adult Older Adult
Onset of illness Abrupt Often insidious
Fever Common May be absent
Chest pain Common Less common
Cough Common Mild or absent
Sputum Productive Often nonproductive
Delirium Infrequent Common
Lungs Consolidation Variable
Hypotension Infrequent Common

Adapted from Yoshikawa TT and Norman DC. Aging and Clinical Practice: Infectious Disease, "Pneumonia", IGAKU- SHOIN Medical Publishers, Inc., New York.

Other clinical findings include: breath sounds dull to percussion, rales are not always present. A respiratory rate of 24/minute is also significantly associated with a pneumonia.

C. Laboratory

1. X-ray - invaluable, especially in demented or delirious patients. The initial X-ray may be normal if the pneumonia is in its early stages, if the patient is significantly dehydrated (an infiltrate may appear after hydration), if the patient is neutropenic with a gram negative pneumonia, or has endobronchial tuberculosis. Obtaining an X-ray may be limited in a confused or agitated patient, severe dyspnea, or the lack of available equipment in the nursing home or physician's office.

2. WBCs & Cultures

  1. Up to 50% of older infected patients will not develop a total WBC outside of the normal range, but 95% of older patients develop a left shift.
  2. Cultures - Blood and sputum cultures should be obtained before empiric antibiotic therapy is started. Up to 25% of patients will be bacteremic. Obtaining a significant volume of sputum is often difficult due the changes discussed above and dehydration. In nursing home patients, ~50% of sputum cultures obtained by transtracheal aspiration revealed only "normal respiratory floral."

D. Causes

1. Community-acquired pneumonia in older patients is caused by a greater diversity of organisms than younger patients.

Streptococcal pneumonia - still the most common organism accounting for 50% of cases.

Hemophilus influenza - responsible for 2 - 20% of cases. Its greater prevalence in the aged may be due to its colonization in the respiratory tract and in patients with chronic bronchitis.

Gram (-) bacteria (GNB) - responsible for 21% of pneumonias in older adults compared to 8% in patients 20-40 years old. The mortality of GNB pneumonias is as high as 70% in persons over the age of 65.

Staphylococcal aureus - pathogen greater prevalence in older persons

Legionella pnuemophilia- pathogen greater prevalence in older persons

Mycobacterium pathogen greater prevalence in older persons

2. Nosocomial Pneumonia (including nursing home acquired pneumonias)

The risk for a nosocomnial pneumonia is 2-3 times greater in patients 60 years than in persons less than 40. An additional risk factor is recent previous) antibiotic therapy.

Streptococcus pnuemoniae, is still most prevalent bacteria, accounting for -33% of cases. However, nearly 50% of all cases are due to a GNB. The most prevalent isolates were (from most-to-least) Klebsiella sp., E. coli, Proteus mirabilis, and Pseudomonas auerugenosa. Hemophilus influenza is also a prevalent bacteria in nursing home acquired pneumonias. Staph.aureus was found in 26% of cultures. Less than 10% of "pure" culture findings implicate anaerobes.

In hospital and nursing home acquired pneumonias, the isolation of a single causative bacteria occurs in less than 50% of cases. In the majority, some combination of gram positive, gram negative and anaerobic bacteria are isolated suggesting aspiration. In theses situations the clinician will feel obligated to continue empiric therapy.

E. Antibiotic Treatment

1. Outpatient treatment of community-acquired pneumonia in older adults. (All treatments are oral and do not require hospitalization)

Marcolides

Dose

Erythromycin  
base, stearate, estolate 250-500mg q 6hrs
ethylsuccinate 400-800mg q 6hrs
Azithromycin 500mg first day, then 250mg/day
Clarithromycin 250-500mg q 12 hrs

Cephalosporins/Carbapenems

Dose

Cefaclor 250-500mg q8hrs
Cefpodoxil 200mg q 12 hrs
Cefuroxime 250-500mg q 12 hrs
Loracarbef 400mg q12hrs

Sulfa

Dose

Trimethoprim/sulfamethoxazole TMP 80 to 160 mg q12hr

Beta-lactam

Dose

Amoxicillin-clavulanic acid 250-500mg q8hrs

NOTE: The quinolone antibiotics have received tremendous support for use in outpatient treatment regimens. Please refer to the reading for specifics relative to dosing and monitoring.

2. Empiric therapy for pneumonia acquired in the community or nursing home (All treatments are IVBP and assume hospitalization).

Patient Characteristics Drug Alternative
Clinically stable Gram stain which indicates a predominant organism Treat according to Gram stain results Treat according to Gram stain results
Sputum unavailable or no predominant organism 2nd generation cephalosporin 3rd generation cephalosporin or clindamycin + aminoglycoside
Toxic, septic, clinically unstable, immunosuppressed, or recently on antibiotics 1st or 2nd generation cephalosporin + aminoglycoside

or 3rd generation cephalosporin +/- aminoglycoside

Penicillin G (or Ampicillin)

+ nafcillin

+aminoglycoside

3. Empiric therapy for pneumonia acquired during an acute hospitalization (All treatments are IVBP and assume hospitalization)

Patient characteristics Drug Alternative
Clinically stable 3rd gen ceph or

2nd gen ceph + pipercillin

clindamycin + aminoglycoside
Toxic, septic, clinically unstable or recently on antibiotics 1st or 2nd gen ceph + aminoglycoside or

Pen G + nafcillin + aminoglycoside

3rd gen ceph +/- aminoglycoside or

vancomycin + clindamycin + aminoglycoside

**** Discussion of specific classes of antibiotics and individual agents are covered in the assigned reading****

G. Treatment of pneumonias in an extended care facility

With the introduction of broad spectrum oral antibiotics, most notably the floroquinolones, physicians may try to treat pneumonias in the nursing home. At times this may be appropriate, specifically when it is the patient's or their guardian’s wishes that the patient not be hospitalized. While the literature on the efficacy of such treatment is minimal, the facility must also be capable of providing other form of support and comfort for the patient. Specifically, 24 hour nursing must be available; ready access to blood gases, microbiology results, blood chemistries and X-rays; oxygen and pharmacy stores must be accessible; and the physician must be available daily and feel comfortable treating a serious infection in this setting.

H. Pneumococcal Vaccine in the Elderly

Pneumococcal pneumonia accounts for an estimated 40,000 deaths each year in the United States. It is still the leading cause of pneumonia in persons 65 years of age. The CDC's Immunization Practices Advisory Committee recommends that all persons 65 years be vaccinated. Most have not been vaccinated. The vaccines efficacy in this population is been controversial with efficacy rates between 44-77%. Persons with chronic diseases (heart, pulmonary or renal), alcoholism or diabetes mellitus appear to have the poorest response. In spite of the controversy, the benefits of vaccination out way the risks.

Revaccination is another area of controversy. When the vaccine was introduced in 1977 it contained 14 types of S. pneumoniae. The current 23-variant vaccine was introduced in 1983. Whether persons who were vaccinated with the 14-variant vaccine should be revaccinated is debatable since the risk for adverse effects (primarily local reactions) is increased. In addition, antibody titers have been reported to decrease in patients with nephrotic syndrome, renal failure or transplant recipients. Revaccination is not routinely recommended unless the person is asplenic, has renal disease, or is at high risk for pneumococcal pneumonia and was vaccinated with the 14-variant vaccine or received the 23-variant vaccine 6 or more years ago.

I. Influenza vaccine and prophylaxis with amantadine

The significance of Influenza A in the elderly is that 80-90% of its mortality occurs in persons 65 years. At present, all persons 65 years old should receive the influenza vaccine annually in October or early November (for persons residing in the Northern Hemisphere). The only contraindication is an allergy to eggs. A thorough immunization program is particularly important in nursing homes where both residents and staff should be immunized. Individuals who are resistant to vaccination should be informed that they can not get the flu from the vaccine since it is not made with a live virus. A method that I have found to sway many older persons into receiving the vaccine is to ask them if they or someone they know remembers the influenza epidemic earlier this century - try it, it works!!! For those persons who can not be vaccinated, refuse, or even though vaccinated are exposed to an influenza A outbreak or develop symptoms amantadine prophylaxis should be offered.

1. Prophylaxis

Amantadine and rimantadine have been shown to be 50-90% effective in preventing influenza A infections. Duration of prophylaxis is between 5 to 7 weeks. Rimantadine was recently approved by the FDA. Its efficacy and adverse effect profile is similar to amantadine.

2. Reduction in symptoms and duration of illness when started within the first 48 hours of symptoms.

3. Mechanism - inhibit viral replication by blocking or reducing the uncoating of viral RNA within the host cell.

4. Pharmacokinetics - eliminated unchanged in the urine by both glomerular filtration and tubular secretion. In older patients, the half-life can be >30 hours or twice that of younger patients. Therefore, persons with renal impairment can have even a greater reduction in clearance.

5. Amantadine Dosing

CrCl (ml/min) Dosing
Normal CrCl, and 65 years old 100mg daily
30 - 50 200mg load x1, then 100mg daily
15 - 29 200mg load x1, then 100mg qod
< 15 200mg once weekly

6. Adverse Effects and Toxicity

One study of retirement home residents found 41% of patients receiving amantadine prophylaxis experienced at least one side effect 22% were severe.

a. Severe - psychosis (9%), hallucinations (13%), seizure (3%), ataxia (11%), falls (11%), and CHF (1%).

b. Moderate - anxiety (13%), nervousness (1%), irritability (5%), fatigue (8%), depression (6%), confusion (11%), impaired concentration (3%), headache (3%), drowsiness (3%), dizziness (11%), slurred speech (3%), rash (3~%)

c. Risk factors - poor health requiring assisted living, multiple medical problems, congestive heart failure and a high serum creatinine. In addition, concurrent drugs with anticholinergic effect should be stopped or their dose reduced.

V. Urinary Tract Infections (UTI’s)

A. General Considerations

1. Factors related to the presence of ~bacteriuria

* sex

* catheters

* functional ability

* fecal impaction

* function and anatomy of the Urinary tract

2. Prevalence

Setting % Elderly Females % Elderly Males
Community 15-30 5-30
Nursing Home 25-50 15-20
Acute Hospital 30 30

B. Etiology - the elderly are similar to other adults with complicated UTI’s

  1. E.coli - most common etiological organism
  2. Other organisms - Klebsiella, Proteus, Enterobacter, Citrobacter, Serratia, Pseudomonas aeur., Enterococcus, and Staph. coag. negative
  3. In the presence of an indwelling catheter, 30% of infections are due to Enterobacter and Gram negative organisms. Bacteriuria, either symptomatic or asymptomatic is universal 30 day after the placement of an indwelling catheter.

C. Clinical Manifestations

The classic symptomatic complaints of dysuria, flank pain, fever and chills may or may not be present. often symptoms are vague or may manifest as another problem such as confusion, hyperglycemia, urinary frequency or incontinence, lethargy, falls, anorexia weakness or decreased mobility.

D. Diagnostic Approach

1. Urine analysis as well as cultures & sensitivity (C&S) should be sent prior to starting antibiotic therapy. The source for the specimen should always be noted. For ambulatory patients urine can be obtained via the midstream clean catch technique, however, many older patients can not perform this task and straight catheterization is recommended. For patients with an indwelling catheter the specimen should never obtained from the catheter bag or tubing since the results may indicate growth in the bag or colonization in the tubing. Instead, the catheter should be removed and a new one inserted from which the sample can be obtained.

2. Blood cultures, electrolytes, CBC

Two sets of blood cultures should be drawn and sent along with a blood chemistries (sodium, serum creatinine, BUN, etc..) and a complete blood count with a differential. These studies are necessary to determine if the patient is septic, dehydrated or developing renal insufficiency that may influence drug selection.

E. Treatment

The choice of empiric therapy should be based on the following parameters:

1) the location of the patient (home, hospital or nursing home)

2) the known flora of bacteria and their sensitivity patterns that frequent the setting

3) previous UTIs experienced by the patient

4) any drug allergies the patient may have

5) whether the patient has been catheterized recently.

Listed below are some general guidelines for treatment.

1. Single dose therapy is NOT effective in the elderly

2. Uncomplicated UTI (oral dosing sufficient)

Trimethoprim 160mg/Sulfamethoxazole 800mg bid x l0-14days OR

-Cephalexin 500mg bid - qid

-Amoxicillin 500mg tid

-Ampicillin 500mg qid

[Note]: Under certain circumstances the use of the amoxicillin-clavulonic acid combination or a quinolone may be appropriate. Avoid the use of nitrofurantoin since it does not achieve high enough urinary tract concentrations in patients with a creatinine clearance below 35 ml/min and can cause peripheral neuropathy and pulmonary fibrosis.

3. Complicated UTI - hospitalize the patient

Empiric treatment - IV 2nd or 3rd generation cephalosporin OR IV Ciprofloxacin

Add an aminoglycoside if necessary.

4. Chronic indwelling catheter

Empiric treatment - Ampicillin 500-1000mg q6h and 3rd generation ceph. if stable

An aminogylcoside if unstable

F. Asymptomatic Bacteriuria -

Bacteriuria in women is defined as two urine cultures with >105 colony forming units (CFU)/mL for the same organism without pyuria within 1 week. In men it is defined as the growth of >103 CFU/mL on a single urine culture. The consensus is that patients who have no symptoms, but positive bacteriuria should not be treated because bacteriuria has not been shown to increase mortality, the risk of adverse reactions and bacterial resistance is great with treatment, and the bacteriuria is often transient. Routine cultures should not be ordered unless the patient becomes symptomatic.

G. Prevention

1. Chemoprophylaxis - to prevent bacteriuria

Indicated for recurrent infections secondary to reinfection when their is normal urinary tract, not for the catheterized patient. * 1/ 2 regular strength TMP 80mg/SMZ 400mg qhs

2. Suppressive chemotherapy prevents symptomatic disease.

May be indicated for the male with asymptomatic bacteriuria with an obstruction (most commonly benign prostatic hyperplasia) who can't or refuses surgery. Usually started after antibiotic therapy for an acute symptomatic infection. *1 regular strength TMP/SMZ bid

VI. Herpes Zoster or "Shingles"

Cutaneous vesicular eruptions followed by radical pain secondary to the recrudescence of the varicella zoster virus which also causes chickenpox.

A. Epidemiology

< 50 years old incidence 2.5/1000 persons

> 80 years old incidence 10/1000 persons

B. Why the recrudescence?

Thought to be related to the decline in cell-mediated immune response.

C. Clinical Manifestations

1. Abrupt onset of pain along a specific dermatome

2. After -3 days a macular erythematous rash appears which become vesicular and pustular, they then dry to a crust and clear in 10 to 21 days.

3. Eruption is primarily unilateral; rarely crossing the midline.

D. Complications

- #1 Postherpetic neuralgia - pain month after rash has healed

- likelihood increases with age: rare <30, 50% in those >60 and >75% in those > 75

E. Treatment-

1. Goal - prevent the post-herpetic neuralgias and relieve discomfort from the lesions

2. Local tx. - aluminum acetate wet-to-wet compress for 30 minutes three times a day until crusting of lesions.

3. Acyclovir - po or iv has been shown to decrease severity and duration of the illness if started within 72 hours of the appearance of the rash. It does not consistently prevent the post-herpetic neuralgias. (valcyclivir is currently available for use as treatment)

Acyclovir - Dose is adjusted based on renal function

CrCl(ml/min)

Dose (po)

Dose(iv)

0-10 200mg q12h 2.5mg/kg q24h
10-25 200mg 5x daily 5.0mg/kg q24h
25-50 800mg 5x daily 5.0mg/kg q12h
>50 "" 5.0mg/kg q8h
Normal "" 10mg/kg q8h

4.Pain

oral analgesics (including antidepressants)

Topical capsacian cream 0.025% or 0.075% applied 3 - 4 times daily. Patients should be warned of a burning sensation an that they may need to apply it less often. Avoid contact with the eyes and mucous membranes; wash hands after applying.

Glucocorticoids - to prevent post-herpetic neuralgias. It is controversial whether prednisone or prednisolone prevent the occurrence of post-herpetic neuralgias. A meta-analysis of published studies concluded that glucocorticoids may have short-term beneficial effect of 6-12 weeks after the onset of rash, but no long-term benefit (24 weeks after rash onset).

Dose: Prednisone 60mg/day x 1 week, then 30mg/day x lweek, and then 15mg/day x 1 week

SELECTED REFERENCES

  1. Warren JW, Palumbo FB, Fitterman L, et al. Incidence an characteristics of antibiotic use in aged nursing home patients. JAGS 1991;39:963-72.
  2. Ljungberg B, Nilsson-Ehle I. Pharmacokinetics of antimicrobial agents in the elderly. Rev Infect Dis 1987;9:250.
  3. Yoshikawa TT. Antimicrobial therapy for the elderly. JAGS 1990;38:1353-72.
  4. Donowitz GR, Mandell L. Beta-lactam antibiotics. NEJM 1988;318:419-26 and 490-500.
  5. Nilsson-Ehle I, Ljungberg B. Quinolone Disposition in the elderly: Practical implications. Drugs and Aging 1991;1:279-88.
  6. Mayer PR, Brown CH, Carter RA, et al. Intramuscular tobramycin pharmacokinetics in geriatric patients. DICP 1986;20:611-5.
  7. Fang G, Brennen C, Wagener M, et al. Use of ciprofloxacin versus use of aminoglycosides for therapy of complicated urinary tract infection: Prospective, randomized clinical and pharmacokinetic study. Antimicrob Agents Chemo 1991;35:1849-55.
  8. Hirata-Dulas CA, Stein DJ, Guay DRP, et al. A randomized study of ciprofloxacin in the treatment of nursing home-acquire lower respiratory tract infections. JAGS 1991;39:979-85.
  9. Peterson PK, Stein D, Guay DRP, et al. Prospective study of lower respiratory tract infections in an extended-care nursing home program: Potential role of oral ciprofloxacin. Am J Med 1988;85:164-71.
  10. Sirgo NA, Norris S. Ceftazidime in the elderly Appropriateness of twice-daily dosing. DICP 1991;25:284-8.
  11. Douglas RG. Prophylaxis and treatment of influenza. NEJM 1990;322:443-50.
  12. Stange KC, Little DW, Blatnik B. Adverse reactions to amantadine prophylaxis in a retirement home. JAGS 1991;39:700-5.

CASE STUDY

Case 1:

JO is an 85 year old white women who has resided in the county nursing home for nearly 5 years. Her medical problems include multi-infarct dementia, a neurogenic bladder for which she has a chronic indwelling catheter, and type II diabetes mellitus which is diet controlled. She has a past medical history of hypertension, but as been normotensive for 4 years without medications. Her functional status is that she is ambulatory, requires assistance bathing and dressing, but can feed herself an perform grooming tasks if cued. Her mental status impairment is manifested by short term memory impairment and occasional disorientation to other persons and place. Her medications consists of only one aspirin a day and she has no known allergies. Her most recent laboratory and vital information is as follows: 2/4/89 - Sodium l40mEq/L, Potassium 3.9mEq/L, Chloride 102mEq/L, CO2 34mEq/L, BUN l0mg/dl, SCr 1.0mg%, and glucose 122mg%

3/3/89 - BP 134/78, HR 70 and regular, Resp. 14/min., and Temp 98.7

On 3/7/89, JO did not eat breakfast or lunch. That afternoon she fell and took to her bed, lethargic, would not answer when spoken to and resistant to having her vitals taken. Later that evening she was calling out "Mother, I don't want to go to school today" and combative when approached. The charge nurse was able to take her vitals which were as follows: BP 110/70, HR 84 an regular, Resp. 18/min and Temp. 99'F. Her mental status was change in that she was oriented only to herself, she was inattentive an did not answer questions appropriately. The nurse called JO physician, who gave the order for JO to be sent to the local hospitals emergency room where she was admitted with the preliminary diagnosis of urosepsis.

Question - What evidence is their that JO has an infection? What are her risk factors?

After admission, blood chemistries, urine analysis, urine and blood cultures were sent (urine was obtained after removing her catheter and inserting a new one). Urine analysis was as follows: color - amber and cloudy, pH 8.0, specific gravity 1.020, glucose negative, protein 30 gm/dl, bacteria -many, WBCs - 50-100/hpf, RBCs 2.. A gram stain of the urine was not done, and cultures and sensitivities are pending.

Blood - Na=132, K=3.8, Cl=100, CO2=30, BUN=16, Scr=1.1, and glucose 220mg%.

Vitals are: BP 120/74, HR 80, Resp 14, Temp.99.4 rectal.

Question - What laboratory information suggests that JO has an infection?

Question - At this point in her hospital course what antibiotic regimen would you recommend and why?

After 48 hours JO's blood cultures are negative, but her urine culture is positive for Proteus mirabilis >105. The organism is sensitive to amikacin, ceftizoxime, ceftazidime, ciprofloxacin, gentamicin, piperacillin, and trimethoprim/sulfamethoxazole, an resistant to ampicillin, cephalothin and nitrofurantoin.

Question - Given the culture and sensitivity results above, do they alter our therapy? If so, what changes would you make?

KEY TO CASE #1

Risk factors include chronic indwelling catheter, diabetes mellitus, dementia, female gender. The fact that she resides in a nursing home is not exactly a risk factor, although the prevalence is greater due to other risk factors which in part explain why the individual is in a nursing home. Signs or symptoms of infection include loss of appetite, a fall, took to her bed, lethargic, would not answer when spoken to and resistant to having her vitals taken, delirium (calling out, combative, and inattentive). Her blood pressure is lower and her heart rate is elevated.

Evidence from urinalysis: color - amber and cloudy, pH 8. 0, protein 30 gm/dl, bacteria -many, WBCs - 50-100/hpf. Evidence from blood chemistries: Glucose of 220mg% even though she has not eaten today. Note: her lower serum sodium (132), BUN and Scr indicate dehydration which commonly accompanies infections in older persons since they tend to stop eating and drinking. A low serum sodium in the face of dehydration is not uncommon since older persons lose their ability to concentrate their urine and conserve sodium. Her vitals: BP 120/74 and HR 80.

Ampicillin lgm IVPB q6 hours and a third generation cephalosporin, an aminoglycoside could be used in place of the cephalosporin if the patient is unstable.

Stop the ampicillin, since the blood cultures were negatives a single agent should be adequate therapy.

Case 2:

It is January and your community is experiencing an Influenza A epidemic. Dr. Maxwell, a local internist, calls you about which of his older patients should be receive amantadine prophylaxis, what adverse effects it can cause and who is most likely to experience them. How do you respond to his queries?

Answers Case 2:

Persons 65 years who were not vaccinated in the fall, persons who develop influenza or its symptoms, and high risk persons or any other person who was vaccinated but would like prophylaxis.

Adverse effects - psychosis, hallucinations, seizures, ataxia, falls, CHF, anxiety, nervousness, irritability, fatigue, depression, confusion, impaired concentration, headache, drowsiness, dizziness slurred speech, and rash.

Risk factors - poor health requiring assisted living, multiple medical problems, congestive heart failure and a high Scr. In addition, concurrent drugs with anticholinergic effects should be stopped or their dose reduced.

 


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