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In the year 2002 people over 60 years constituted 16% of the population,
and people 65 years and older represented 12% of the population (US
Census Bureau \http//www.census.gov>). By the year 2050, the number of
Americans over 65 years of age is estimated to double to reach nearly 80
million. Despite the many advances that have occurred in the prevention,
diagnosis, and treatment of infectious diseases, infections still cause severe
morbidity and mortality in the elderly and are the most frequent cause of
hospitalization in this population.
Managing infections in the elderly is a challenge for a number of reasons.
Diagnosis of infections can be problematic, because elderly patients
frequently lack classical signs and symptoms of infection, such as fever
and leukocytosis. When infection occurs, the elderly often present with
unusual symptoms, such as poor appetite, dehydration, functional impairment, and changes in cognition. Physical ndings and laboratory results
are often dicult to interpret because many of the elderly have baseline
pulmonary, urinary tract, and laboratory abnormalities (eg, rales, bacteriuria, and pyuria). Therapy is problematic in the elderly because of the
increased potential for toxicity of antimicrobial agents and adverse drug
reactions caused by polypharmacy.
The following sections discuss some of the important physiologic
changes, drug-drug interactions, compliance issues, and reasons for increased adverse eects that aect use of antimicrobial agents in the elderly.
There is also a review of the most frequently encountered bacterial
infections in the elderly and recommendations for therapy.
It is estimated that more than 40% of the persons aged 65 years require
care in a long-term care facility (LTCF) or skilled nursing facility at some
point in their lifetime [1]. Special comments about patients in LTCF are
* Corresponding author. 1305 Cooper Circle, Audubon, PA 19403.
E-mail address: malastalam@aol.com (M. Stalam).
0891-5520/04/$ - see front matter 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.idc.2004.04.004
534
CLcr
140age y weight kg
0:85 in women
Cr mg=dL 72
The major drawback to using this equation is that it requires using the
patients ideal body weight. This may be dicult to determine, especially in
morbidly obese or edematous patients. Furthermore, the serum creatinine
value may be spuriously low in the elderly because of malnutrition and
decreased muscle mass. Often creatinine values within normal limits indicate
varying degrees of renal insuciency. For example, a serum creatinine of
1 in a frail 85-year-old woman weighing 86 lb may represent a creatinine
clearance as low as 25 mL/min.
Drugdrug interactions
Elderly patients are frequently taking a number of medications, such as
anticoagulants, antiarrhythmics, antihypertensives, antidepressants, and
antiseizure agents. Residents of LTCF receive an average of 5 to 10 prescribed drugs each day [4]. Table 1 lists some of the antibiotics commonly
used in the elderly and examples of drug-drug interactions that can occur.
535
Table 1
Selected drug- drug interactions
Antibiotic
Drugs
Interaction
Aminoglycosides
Loop diuretics
NSAIDS
Radiographic
contrast
Vancomycin
Allopurinol
Anticoagulants
Theophylline
Antiarrhythmics
Increase in ototoxicity
Increase in nephrotoxicity
Adrenergic agents
Serotonergic drugs
Cisapride Pimozide
Ampicillin, amoxicillin
Some cephalosporinsa
Ciprooxacin
Gatioxacin, levooxacin,
moxioxacin
Linezolid
Macrolides
Erythromycin,
clarithromycin
Metronidazole
Tetracyclines
Trimethoprim
Lovastatin
Simvastatin
Warfarin
Digoxin
Digoxin
Potassium-sparing diuretics
Compliance
Elderly patients have been perceived as being noncompliant with drug
regimens. Compliance remains a challenge especially in view of frequent
polypharmacy and may drop to 50% for oral therapy [5]. Some of the
reasons for noncompliance in this population are as follows:
1. Inability to follow directions (ie, to be taken on empty stomach or 1
hour before meals or to avoid antacids)
2. Fear of drug-drug interactions
3. Attributing unrelated symptoms as secondary to antibiotic intake (eg,
diaphoresis, palpitations, dizziness)
4. Improvement of symptoms and return to sense of well being
5. Symptoms did not improve despite several doses
6. Difculty in opening child-resistant containers
7. High cost of medications
8. Perceived need to save medication in case infection recurs
9. Impaired vision or difculty in hearing
10. Poor memory
Compliance can be improved by better communication between patient
and caregiver (eg, providing the patient with written and oral instructions);
536
Etiologic bacteria
Community-acquired pneumonia
in otherwise healthy
537
538
539
540
aeruginosa): piperacillin-tazobactam, ceftazidime, cefepime, imipenem, meropenem, and aztreonam. An aminoglycoside, such as gentamicin, is added
to the b-lactam antibiotics for its synergistic killing eect especially for
infections caused by P aeruginosa. If there is a history of hypersensitivity to
b-lactam antibiotics, aztreonam is the b-lactam least likely to result in
a reaction. If ciprooxacin is not included in the regimen, a macrolide may
be added for activity against atypical bacteria, such as Legionella. Aminoglycosides must be used with care, and peak and trough levels followed,
because of the increased occurrence of nephrotoxicity and ototoxicity in the
elderly. If an aminoglycoside is contraindicated, a uoroquinolone active
against P aeruginosa (ie, ciprooxacin) may be added to a b-lactam
antibiotic. As an alternative to use of b-lactam antibiotics, ciprooxacin
can be used together with an aminoglycoside. Vancomycin should be added
to the regimen unless MRSA is ruled out. Nafcillin is preferred for
methicillin-susceptible S aureus. Therapy is modied when results of
cultures and sensitivity studies are available. Hospital-acquired pneumonia
usually requires at least 10 to 14 days of therapy [35]. A recent study,
however, suggested that 8 days of appropriate therapy may be sucient in
some cases [36].
Prevention
Pneumonia and inuenza are the fourth leading cause of death among the
elderly [37]. Many cases of pneumonia can be prevented in the elderly by the
simple adherence to universal administration of pneumococcal vaccine and
yearly immunization against inuenza. Although the ecacy of inuenza
vaccine is reduced in the elderly, even in residents of LTCF it prevents 70%
to 80% of deaths from pneumonia following inuenza [38].
Pneumococcal polysaccharide vaccine is a 23-valent vaccine containing
the polysaccharide antigens of pneumococcal serotypes that cause more
than 90% of invasive pneumococcal infections. Case control and indirect
cohort studies indicate an ecacy of 60% to 70% in preventing invasive
pneumococcal infections [39,40]. Pneumococcal vaccine should be administered to patients 65 years of age and older if their prior vaccine history is
not known, because the incidence of adverse events is as low following
revaccination as it is following initial vaccination [41]. Despite of its ecacy
and safety, many people aged 65 years and older do not get vaccinated.
541
Table 3
Factors contributing to bacteriuria
Women
Men
542
543
544
streptococci or staphylococci. Antistaphylococcal penicillins, rst-generation cephalosporins (eg, cefazolin or cephalexin) or clindamycin are
commonly used to treat cellulitis caused by methicillin-susceptible S aureus
and streptococci. With deeper diabetic foot ulcers or ulcers caused by
peripheral vascular disease, however, polymicrobial infection with staphylococci, aerobic gram-negative bacilli, or anaerobes is common [61]. Broadspectrum antibiotic therapy is necessary for empirical treatment of cellulitis
in the presence of deep diabetic ulcers or ulcers from peripheral vascular
disease. Patients with these types of cellulitis should receive therapy active
against gram-positive and gram-negative aerobes and anaerobes. Vancomycin, linezolid, or quinupristin-dalfopristin must be used when serious
infection with MRSA is suspected. Linezolid has the advantage of being
available in oral form, which can be used after initial clinical response. In
cases of deep wound infection and osteomyelitis adequate surgical debridement is essential for cure.
Clostridium dicileassociated diarrhea
Epidemiology
Clostridium dicileassociated diarrhea is usually a complication of
antibiotic therapy and is a major cause of nosocomial infectious diarrhea
and common cause of acute diarrheal illness in LTCF [6264]. It is most
likely to occur in hospitals and less frequently in LTCF. Older age is a risk
factor for CDAD because the incidence increases dramatically in those over
60 years of age [65]. Although virtually any antimicrobial agent can be
associated with CDAD, most cases have occurred as a complication of use
of clindamycin or b-lactam antibiotics. C dicile colonization and CDAD
occur commonly in elderly LTCF residents. Contributing factors in LTCF
are thought to be the closed environment; contaminated inanimate objects
(eg, commodes); fecal incontinence; and a higher rate of exposure to
antibiotics [66].
Therapy
Metronidazole is the antibiotic of choice and should be given orally or by
a feeding tube. It can be used parenterally, if necessary, because adequate
amounts of drug reach the gastrointestinal tract when it is injected.
Vancomycin, which is much more expensive, should be avoided because
of the potential for facilitating the spread of vancomycin-resistant enterococci [67]. If used for CDAD, vancomycin must be given orally or by
a feeding tube. Parenterally administered vancomycin does not reach the
gastrointestinal tract and is of no value in treating CDAD. Therapy should
be continued for 7 to 10 days.
Prevention and control of CDAD in LTCF involves prudent use of
antimicrobials; providing a private room if possible for residents with fecal
545
incontinence; avoiding sharing patient care items (eg, stethoscope and blood
pressure cus); and disinfecting room surfaces of residents with CDAD
using dilute hypochlorite solution [68].
Resistant pathogens in long-term care facilities
The most frequently encountered resistant pathogens in LTCF are
MRSA, vancomycin-resistant enterococci, and multidrug-resistant gramnegative bacilli. Up to 25% of patients with MRSA colonization can
develop MRSA infections [69]. In residents with vancomycin-resistant
enterococci colonization, however, the rate of infection caused by vancomycin-resistant enterococci is low [70].
Predisposing factors for colonization with resistant pathogens are
frequent hospitalizations, decreased functional capacity, presence of urinary
catheter, tracheostomy, feeding tube, decubitus ulcer, and use of antibiotics
[55,71].
It is dicult to implement infection control guidelines in LTCF similar to
those in acute care facilities. Some of the limitations are a limited number of
single rooms; the cost of performing surveillance cultures; and the negative
aspects of isolation of LTCF residents, which restricts their functional
capacity and quality of life. Quality of life is an important priority in LTCF.
To prevent spread of these resistant pathogens, keeping decubiti (and other
colonized lesions) covered, judicious use of antibiotics, use of gloves by
caregivers, and using alcohol-based hand antisepsis are preventive methods
that can be implemented [55].
Summary
Changes that occur in the pharmacology of drugs in the elderly must be
considered in the use of antimicrobial agents. Although absorption of orally
administered drugs is not aected in a signicant way, renal function
decreases, drug-drug interactions increase, compliance with regimens may
be decreased, and drug toxicity is increased. The most frequent infections
occurring in the elderly are pneumonia, urinary tract infection, and soft
tissue infection. CDAD is usually a complication of antibiotic therapy.
Pneumonia can be categorized as community-acquired, LTCF acquired, and
hospital-acquired. Therapeutic approaches vary according to which of these
sites is involved. Urinary tract infection is divided into upper tract infection,
lower tract infection, and asymptomatic bacteriuria. Upper tract infection is
treated for a longer period of time than lower tract infection and
asymptomatic bacteriuria is usually not treated. Soft tissue infection is
usually caused by an infected pressure ulcer or cellulitis (which may be
a complication of a diabetic foot ulcer or an ulcer caused by peripheral
vascular disease) and may be supercial or deep. These infections have
dierent microbial causes and require dierent therapeutic approaches.
546
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