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Antimicrobial prescribing
in older adults
Abstract: Infectious diseases pose a significant threat to older adult health and
well-being. Determining the appropriate use and selection of antimicrobials in older
adults can be challenging. Age-related physiologic changes, multiple comorbidities,
and polypharmacy are factors that can make prescribing antimicrobials
complicated and the effectiveness of therapy unpredictable.
By Gloria L. Brandburg, PhD, RN, GNP-BC
I
nfectious diseases can pose a major threat to
anti microbial drug resistance and the need for im
older adults. Susceptibility to infection in-
proved stewardship.
creases with age, and treatment is often com-
It is estimated that at least 30% of antibiotics pre
plex due to multiple comorbidities and decreased
scribed in the US are not needed.2 Judicious use of
organ functional reserves. Older adults can present
antimicrobials is warranted because adverse drug reac
atypically with infections, which increases the risk of
tions and Clostridium diff cile infection (CDI) are lead-
a delayed or missed diagnosis.1 Common infections in
ing causes of morbidity and mortality in older adults.3
older adults include pneumonia, urinary tract infec-
CDIs are becoming more prevalent, including antibi
tions (UTIs), skin infections, and chronic disease ex-
otic-resistant strains that can often lead to
acerbations (which may also require antimicrobial
hospitalizations in older adults.3 Polypharmacy, poor
treatment). However, the frequent use of antimi-
adherence to treatment, greater severity of illness, and
crobials in older adults has led to concerns about
comorbidities are common factors in older adults that
Keywords: antibiotic resistance, antibiotic stewardship, antibiotic use, antimicrobials, geriatrics, infectious disease, older adults
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Immunosenescence affects all branches
of the immune system (cellular, humoral,
and innate immunity).

Copyright (c) 2019 Wolters Kluwer Health, Inc. All rights reserved.
can impact treatment success. Increased individual
variation secondary to altered pharmacokinetics and
pharmacodynamics also makes prescribing a challenge
in these patients.1,4,5
 Aging immune system and risk of infection
Age-related physiologic changes place older adults at
higher risk for infectious diseases. Immunosenescence
affects all branches of the immune system (cellular,
humoral, and innate immunity). Signifi cant changes
include atrophy of the thymus, a reduction in lym
phocytes, altered B- and T-cell function, changes in
cytokines and growth factor secretion, and changes
in antibody production and antibody response.
By age 75, the thymus gland is
nothing more than fatty scar tissue.
It is responsible for T-lymphocyte
development in childhood that will
last a lifetime; the total number of
T-lymphocyte cells does not signifi 
cantly decrease with age, but the T-
cell subset populations change.6 The cumulative effects
of aging on T-helper cell function are most pronounced,
affecting both cellular and humoral immunity. T-cell
mediated defects increase the risk of intracellular patho
gens, such as Listeria monocytogenes, Salmonella spp.,
Legionella spp., and mycobacterial infections.5
Although B-cell numbers are not significantly
affected by aging, B-cell ability to respond to antigens
is limited. Encapsulated bacteria such as Streptococcus
pneumoniae are associated with B-cell mediated defects
and lowered antibody production.1 There can also be a
reduced response to immunizations and reactivation of
latent infections, such as Mycobacterium tuberculosis and
varicella-zoster virus.5 Overall, fewer mature B and T
cells are produced with age.7 Chronic low-grade infl am
mation in older adults that can be observed by increased
proinflammatory cytokines, such as interleukin-6 and
tumor necrosis factor-alpha, can further compromise
the immune system.7
The effects of proinflammatory cytokines include
oxidative stress, lowered antioxidants, and increased
cortisol levels that can further accelerate the decline
in immunity.7 Changes in growth factor secretion
associated with aging have implications in the devel
opment of cardiovascular disease, type 2 diabetes
 mellitus (T2DM), and retinal eye disease.8
The most common infectious diseases among older
adults are UTIs, lower respiratory tract infections, and
Antimicrobial prescribing in older adults
skin and soft tissue infections that occur across settings
(community, hospital, or long-term-care [LTC] facili
ties).1,5 Bloodstream infections are more likely to be
found in the hospital, and gastrointestinal (GI) infec
tions are more common in community dwellers and
LTC facility residents.1
Comorbidities in the older adult population-
particularly chronic cardiac and pulmonary diseases-
can increase susceptibility to infection. Comorbid
conditions include chronic inflammatory diseases
(chronic obstructive pulmonary disease, atherosclero
sis, diabetes mellitus) that produce proinfl ammatory
cytokines and have been linked to higher risk for infec
tions, such as pneumonia.7,9 Medical devices such as
indwelling urinary catheters, joint prostheses, pace
makers, and artifi cial cardiac valves can also be risk
factors for infection.1
Older adults living in institutions are particularly
challenged in host defenses and environmental risk
factors. Host defenses in this population can be com
promised by dysphagia, malnutrition, and poor oral
hygiene, which are often related to dementia. Com
munal living can promote rapid transmission of
respiratory and GI infections, including multidrug
resistant organisms. The severity of infection increases
with age, and prognosis of recovery has been linked
to functional status in those over age 80, leaving LTC
facility residents at a high risk for poor outcomes,
including death.5,10
 Atypical presentation of infectious disease
in older adults
Ms. M, 75, lives in an LTC facility. She has a history of
hypertension, chronic kidney disease (stage 2), and
T2DM. The nursing staff reports a decrease in her ap
petite and a decline in her ability to participate in activi
ties of daily living. Ms. M complains of being tired and
not feeling like her normal self but offers no other specif c
complaints. She is afebrile.
Diagnosis of an infection may be delayed in part
because of the unusual way older adults present with
the signs and symptoms of illness. This can be further
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Copyright (c) 2019 Wolters Kluwer Health, Inc. All rights reserved.
Antimicrobial prescribing in older adults
complicated by the presence of comorbidities that the
clinician may consider as the cause of the complaint
instead of infection. The added challenge of cogni
tively impaired older adults who may not be able to
provide a history of present illness requires even more
vigilance from the clinician. The usual febrile response
that accompanies infection may be blunted, absent,
or have a delayed onset, such as with Ms. M in the case
example.1,5
Normal baseline temperature of older adults is
lower than younger adults, and this can lead to missing
a significant rise in body temperature. Furthermore,
other signs of inflammation, such as leukocytosis, may
not be present. Approximately half of older adults with
an infection will not have localizing symptoms or
findings on physical exam that suggest infection, and
that same percentage will have normal lab results.1
The blunted or lack of inflammatory response is
largely responsible for this unexpected or atypical
presentation. Therefore, it is essential that infection be
considered in older patients even if the signs of
Effects and implications of aging on
pharmacokinetics12,13
Absorption: Aging can increase gastric pH, decrease
absorptive surface area, decrease splanchnic blood fl ow,
decrease GI motility, and delay gastric emptying. The rate
of absorption may be slowed, and drugs requiring a
high-acid environment may have reduced absorption.
Less drug absorption means less clinical effi cacy.
Distribution: Older adults have higher body fat, decreased
lean body mass, decreased total water, decreased serum
albumin, and decreased cardiac output. Lipid-soluble
drugs may be stored longer in the body; concentrations
of water-soluble drugs may be increased. The number
of sites where drugs bind to protein will be decreased,
causing an increase in free drug levels. Only unbound or
free drugs are able to reach their site of action. Bound
drugs can lower therapeutic drug levels, leading to a
blunted or no response to treatment; free drugs can lead
to toxicity and overdose.
Metabolism: Decreased hepatic blood fl ow, decreased
hepatic mass, and decreased activity of hepatic enzymes are
associated with aging. Half-life of drugs increases, giving a
prolonged drug effect. First-pass metabolism is decreased,
leading to higher active drug levels in circulation.
Excretion: Aging is associated with decreased renal blood
flow, decreased glomerular filtration rate, decreased
tubular secretion, and decreased number of nephrons.
Creatinine clearance can be used as an index of kidney
function in older adults, however it may be normal due to
decline in muscle mass, so levels may be normal in
reduced kidney function.
inflammation are absent; however, diagnostic criteria
for the specifi c infection should be met before pre
scribing antibiotics.1,5,11 The McGeer  Criteria for Infec
tious Syndromes in Older Adults is a helpful evidence-
based framework for clinicians who are trying to
diagnose infections in older adults.1,11
 Pharmacodynamics and pharmacokinetics
in older adults
There is no clear and definitive picture of pharmaco
dynamics and aging. Changes in how the aging body
responds to a given drug may be related to several fac
tors, such as the availability of receptors (increase or
decrease), receptor affinity, and postreceptor alterations.
A receptor can be defined as any functional macromol
ecule in a cell to which a drug binds to produce its ef
fects. For example, beta-adrenergic blocking agents are
generally less effective in older adults than in younger
adults, even when they have the exact same drug con
centrations. It could be a reduction of beta-receptors
in older adults or a reduction in the affinity of the beta-
receptor for the agent that produces this change in drug
response.12,13
Older adults may experience more intense effects
of drugs, which suggests a possible increase in receptors,
stronger receptor affinity, or both. Affinity refers to the
strength of the attraction between a drug and a receptor.
Examples of drugs that produce strong effects in older
adults include warfarin and central nervous system
depressants. Impairment of homeostatic mechanisms
such as fluid and electrolyte balance and acid-base bal
ance can also play a role in how the body responds to a
certain drug. It can be difficult to predict drug response,
as age-related changes can vary greatly from person to
person. There is limited information on the pharma
codynamics of antimicrobials in older adults, but it
should be considered when a drug does not have the
desired effect.12
Disease and the aging process can affect all phases
of pharmacokinetics. The extent of age-related changes
varies greatly among patients because general health
and fi tness are major contributors to a slower aging
process. Starting in early adulthood, there is a gradual
and progressive decline in organ function. Reduced
hepatic and renal function has the greatest infl uence on
the body's sensitivity to drugs. Pharmacokinetics is how
drugs move through the body in four phases: absorp
tion, distribution, metabolism, and excretion (see Effects
and implications of aging on pharmacokinetics).9
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Copyright (c) 2019 Wolters Kluwer Health, Inc. All rights reserved.
 General considerations
A long-standing clinical pearl for prescribing drugs to
older adults is to "start low and go slow" when initiating
and titrating drug therapy; however, this approach can
lead to suboptimal clinical outcomes, particularly with
antimicrobial therapy. It can be a delicate balance to
provide aggressive antimicrobial dosing to achieve a
satisfactory clinical response without doing harm to the
aging body.1 Adverse drug reactions (ADRs) are seven
times more likely to occur in older adults than younger
adults. ADRs account for 16% of hospital admissions
and 50% of medication-related deaths in older adults.13
The increase in ADRs is related to multiple factors
that often accompany the aging process, including
greater severity of illness, the presence of comorbidities,
inadequate supervision of therapy, and poor patient
adherence.1,9 The majority of ADRs in older adults can
be avoided by taking a few measures that are effective
in reducing their incidence:13
-  Take a thorough drug history, including over-the-
counter medications, to decrease the incidence of
drug-to-drug interactions.
-  Consider pharmacodynamic and pharmacokinetic
changes that may occur with aging and understand
that there is wide individual variation.
-  Start at a low dose if indicated.
-  Closely monitor plasma drug levels if indicated and
the clinical response.
-  Order the simplest treatment regimen possible.
Careful consideration of potential drug-to-drug in
teraction is important when prescribing antimicrobials
(see Common antimicrobial-induced interactions and
adverse reactions in older adults).1,11,13 Commonly used
drugs in older adults can potentially interact with
many antimicrobials, including warfarin, loop diuret
ics, digoxin, antacids, and proton pump inhibitors
(PPIs). In some cases, another class of anti microbial
is indicated, whereas in others, increased patient moni
toring will suffice. For example, frequent monitoring
of the international normalized ratio (INR) for pa
tients taking warfarin is warranted because studies
show exposure to a variety of antimicrobial agents
(azoles and other classes of antifungals, macrolides,
trimethoprim/sulfamethoxazole, penicillins, and ceph
alosporins) is associated with increased bleeding.14
A baseline kidney function test and ongoing moni
toring during therapy are warranted prior to starting
aminoglycosides.13 It is essential that the prescriber
knows all medications the patient is taking as well as
Antimicrobial prescribing in older adults
accurate information on alcohol, tobacco, and recre
ational drug use to minimize drug-to-drug interac
tions. This includes the type of substances used, how
often, and for how long the patient has been using
them. Abstaining from alcohol is important whenever
drug-induced hepatitis is a concern (for example, with
antifungal medications).12,13
Common medications can interact with antimi
crobials. For example, HMG-CoA reductase inhibitors
(statins) can interact with certain macrolides to in
crease the risk of rhabdomyolysis by inhibiting the
CYP3A4 isoform of cytochrome P450. Fortunately,
azithromycin, a commonly prescribed macrolide, does
not inhibit CYP3A4, but clarithromycin and erythro
mycin do.14 Older adults with T2DM may  experience
severe hypoglycemic episodes when taking certain
antimicrobials. The underlying mechanism is likely
that certain antimicrobials may inhibit the CYP2C9
mediated sulfonylurea metabolism, causing increased
bioavailability of sulfonylurea medication; however, it
is equally important to be aware that clarithromycin
and fluoroquinolones should be used with caution in
patients with diabetes mellitus and avoided if
possible.14
Another major contributing factor in ADRs in older
adults is polypharmacy. Polypharmacy is often defi ned
as taking five or more medications, but it can be medi
cally necessary to use multiple medications to treat a
chronic disease. In addition, older adults can have mul
tiple chronic diseases, allowing this threshold to be
easily met or exceeded. There should be a diagnosis for
each drug the patient is taking. It is also important to
include start and stop dates for antimicrobials and to
set times to evaluate response to treatment. Long-term
use of antimicrobials should also be evaluated for ef
fectiveness and necessity to continue.4,10
As the number of medications taken rises, the risk
of drug-to-drug interactions also rises. In 1 year, the
average older adult with five or more chronic illnesses
will see 11 different providers, make 37 provider offi ce
visits, and fi ll 50 prescriptions.1 This reinforces the
importance of having a primary care provider coor
dinate the patient's overall treatment plan. Technology-
driven prescribing with electronic prescriptions can
assist in alerting providers to  potential drug-to-drug
interactions and polypharmacy issues via the  electronic
health record. Asking patients to bring all current
medications to each clinic visit so a review can be
completed is recommended.4
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Copyright (c) 2019 Wolters Kluwer Health, Inc. All rights reserved.
Antimicrobial prescribing in older adults
Common antimicrobial-induced interactions and adverse drug reactions in older adults
Selected
Commonly used drug
Possible drug-drug interaction
Adverse drug reactions/
antimicrobials
in older adults
implications
Penicillins
Diuretics
Potassium wasting may increase
Hypokalemia; monitor electrolytes
Warfarin
Increased or decreased warfarin
Increased risk of bleeding or
effects (depends on the specifi c
decreased therapeutic effect;
penicillin)
monitor INR
Ampicillin
Beta-blockers
May reduce the bioavailability
Worsening hypertension; select
of atenolol
another penicillin
Allopurinol
Higher incidence of drug rash
Rash; avoid coadministration
All cephalosporins
Loop diuretics
Increased risk of nephrotoxicity
Monitor kidney function closely
Warfarin
Increased warfarin effects
Risk of bleeding; monitor INR
Cefotetan
Ethanol
Acute disulfiram-like reaction
Avoid concurrent alcohol
consumption
Cefaclor, cefdinir,
Antacids
Reduced plasma concentrations
Separate administration by at least
cefpodoxime
2 hours; if appropriate, substitute
(extended-release)
cefprozil because it is not affected
by antacids
All fl uoroquinolones Antacids, bismuth,
Interferes with GI absorption of
Separate antacids and mineral
subsalicylates, mineral
the fl uoroquinolone
supplements by 2 to 4 hours
supplements
Antidiabetic drugs
Increase or decrease in blood
Increase glucose monitoring
glucose levels
Classes 1 and 3 anti-
Increased risk of fatal
Select different antibiotic
arrhythmics
dysrhythmia
Glucocorticoids
Concurrent use increases risk of
Select different antibiotic
tendon rupture/tendonitis
Warfarin
May increase anticoagulant
Monitor INR
effects
All macrolides
Methadone
Prolonged QT interval
Avoid concurrent use
Digoxin
May elevate digoxin levels
Monitor for signs and symptoms
of digoxin toxicity
Aminoglycosides
Ethacrynic acid
Increased ototoxicity
Select a different loop diuretic,
such as furosemide, bumetanide
Nonsteroidal anti-
Increased nephrotoxicity
Discontinue during therapy;
infl ammatory drugs
monitor kidney function and
(NSAIDs)
drug levels
Oxazolidinones
Selective serotonin
Serotonin syndrome
Monitor for signs and symptoms
reuptake inhibitors, tri
of serotonin syndrome, use if no
cyclic antidepressants
other alternative
Tramadol, methadone
May be a significant increase in BP
with tyramine-rich food and drinks
Trimethoprim/
Sulfonylureas
Increased half-life of sulfonyl-
Hypoglycemia
sulfamethoxazole
ureas
Trimethoprim
Angiotensin-converting
Decreased potassium excretion
Hyperkalemia
enzyme (ACE) inhibitors
and angiotensin II recep
tor blockers
Nitrofurantoin
Anticholinergics
Increased absorption of nitro-
Increased risk of ADR and toxicity
furantoin
(continued on next page)
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Antimicrobial prescribing in older adults
Common antimicrobial-induced interactions and adverse drug reactions in older adults (continued)
Selected
Commonly used drug
Possible drug-drug interaction
Adverse drug reactions/
antimicrobials
in older adults
implications
Tetracyclines
Antacids, iron
Impaired absorption
Separate doses by 2 hours and
take antibiotic class fi rst
Warfarin
May increase warfarin effects
Choose a different antibiotic if
possible; monitor INR
Digoxin
May increase digoxin levels
Select a different antibiotic class
Insulin
May reduce insulin requirements Monitor blood glucose closely
Glycopeptides
ACE inhibitors, loop
Increased risk of nephrotoxicity
Monitor kidney function closely
diuretics, NSAIDs
Antimycobacterials
Digoxin
May decrease digoxin levels
Monitor digoxin levels
Streptomycin
Loop diuretics
Increased risk of ototoxicity
Avoid concurrent use; hearing loss
may be permanent
Nucleoside
Probenecid
Increased serum levels and
Avoid concurrent use
analogues
terminal half-life of acyclovir
Antifungals
Hydrochlorothiazide
Increase in fluconazole
Avoid concurrent use
Fluconazole
Phenytoin
Increase in phenytoin
Monitor phenytoin levels
Sulfonylureas
Hypoglycemia
Monitor glucose levels
Warfarin
Increases warfarin effects
Monitor for bleeding and INR
Ketoconazole
Antacids, H2 blockers,
Inhibited ketoconazole absorption
Avoid concurrent use
PPIs
Corticosteroids, warfarin
Ketoconazole decreases metabo-
Monitor INR closely
lism of these drugs
Terbinafine
Alcohol
Increased risk of liver damage
Abstain from alcohol while on
terbinafine; monitor liver enzymes
Phenytoin
Increased metabolism of
Avoid concurrent use
terbinafi ne
Caffeine
Decreased metabolism of caffeine Reduce use of caffeine
Metronidazole
Warfarin
Warfarin increased
Monitor INR
Alcohol
Disulfiram-like reaction
Abstain from alcohol
Adapted from Burchum JR, Rosenthal LD. Lehne's Pharmacology for Nursing Care. 9th ed. St Louis, MO: Elsevier Saunders; 2016:92-95;
Woo TM, Robinson MV. Pharmacotherapeutics for Advanced Practice Nurse Prescribers. 4th ed. Philadelphia, PA: F.A. Davis Company; 2016.
Mr. K, 60, lives in an assisted living facility. He had
a stroke 3 years earlier. He has some mild short-term
memory defcits and right hemiplegia. Mr. K comes to
the clinic because of a nagging cough after a recent upper
respiratory infection. The cough is productive with small
to-moderate amounts of yellow sputum. He also com
plains of chest discomfort with the cough but denies any
fever or chills. Mr. K is worried that he has pneumonia
and wants an antibiotic. He is given a prescription for
azithromycin.
Antimicrobial resistance is a growing problem, and
the leading risk factors for having a drug-resistant
pathogen include recent use of antibiotics, age younger
than 2 years or older than 65, day-care center attendance,
exposure to children, multiple comorbidities, recent
hospitalization, and immunosuppression.15 Outbreaks
of multidrug-resistant organisms are often reported in
LTC facilities. Colonization with resistant pathogens
occurs in both institutionalized and community-
dwelling older adults.5 Excessive and inappropriate use
of antimicrobial agents is a major factor in the develop
ment of drug resistance.2 Common examples include
the use of antibiotics in viral infections, inadequate
dosing, excessive duration of therapy, and increased
empirical use of broad-spectrum antibiotics when not
required.11
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Copyright (c) 2019 Wolters Kluwer Health, Inc. All rights reserved.
Antimicrobial prescribing in older adults
In the case of Mr. K, he likely has a viral infection
with acute bronchitis, and antibiotics would not be
indicated. Antimicrobial stewardship strategies include
meeting diagnostic criteria for an infectious disease,
treatment pathways for specifi c infectious diseases,
formulary restrictions, dose optimization, prospective
audits of prescribed antimicrobials, and continuing
education for prescribers.10,16
Drug therapy based upon culture and sensitivity
specimen reports using the drug with the lowest mini
mum inhibitory concentration is preferred.15 However,
this is not always feasible in primary care clinics due to
lack of insurance coverage, so treatment may be de
layed. Consider obtaining a culture and sensitivity
specimen if there is no response to treatment within
48 hours. Duration of therapy should be the shortest
recommended length. These considerations highlight
the importance of timely follow-up with the patient
when prescribing antimicrobials.
In addition to the concern about the development
of drug-resistant organisms, there is the negative effect
of anti biotic exposure on the older adult's microbiome.
The most common example is CDI. C. diffcile is an
anaerobic, Gram-positive, spore-forming, toxigenic
bacterium that is one of the most common causes of
healthcare-acquired diarrhea in the US.17 Antibiotic-
associated pseudomembranous colitis pathogenesis
begins with alteration of the normal microflora due to
antibiotic exposure in the gut.18
Older adults are more susceptible to CDI due to
age-related decline in immunity and are at higher risk
for the more severe form of infection. Patients over age
65 have a greater chance of developing CDI compared
with younger patients.18 Long-term PPIs may also be
an additional risk factor for CDI. This risk is related to
the reduced gastric acid secretion that may allow C.
difficile to survive longer in the GI tract.17 It is not
uncommon for older adults to be on long-term PPIs;
this serves as a reminder to discontinue antiulcer
and gastroesophageal reflux disease medications that
are no longer needed. However, there is no recommen
dation for discontinuing PPIs as a preventive measure
for CDI.17
 Conclusion
There are many considerations when prescribing anti
microbials to older adults. The aging immune system
impacts infection risk and severity, which at times
makes recognizing an infection diffi cult. Aging alters
pharmacokinetics and pharmacodynamics in ways
that increase ADRs and suboptimal treatment success.
Comorbid conditions with multiple  prescribers in
crease the risk of drug-drug interactions. The growing
problem of antibiotic resistance and CDI highlights
the need for antibiotic stewardship. Prescribers must
be diligent to prevent unnecessary antimicrobial use
and when used to monitor the older adult's  response
closely.
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Gloria L. Brandburg is an associate professor at the University of Texas Medical
Branch, School of Nursing, Galveston, Tex.
The author has disclosed no financial relationships related to this article.
DOI-10.1097/01.NPR.0000524666.24469.d1
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