Antimicrobial Resistance
Antimicrobial Resistance
Antimicrobial Resistance
CLINICAL PHARMACOLOGY
Antimicrobial Resistance:
A Plan of Action for Community Practice
THOMAS M. HOOTON, M.D., University of Washington School of Medicine, Seattle, Washington
STUART B. LEVY, M.D., Tufts University School of Medicine, Boston, Massachusetts
S
ince their introduction in the morbidity and mortality. Compounding
1940s, antibiotics have been the this public health crisis is the fact that
primary treatment for bacterial few novel agents are being developed for
infections. Although antibiotics use in the future.
were once hailed as “miracle The growing sense of urgency surround-
drugs” without adverse consequences, ing the problem of antibiotic resistance was
widespread and often inappropriate use heightened recently by alarming reports of
has contributed to the emergence of bac- community-onset infections caused by
teria that are resistant to not just one, but strains of methicillin-resistant Staphylo-
multiple antibiotics. coccus aureus (MRSA) in Minnesota and
Most concerns about resistance have North Dakota.1 Although MRSA infec-
focused primarily on hospitals and the tions were once confined to patients in
developing world, seemingly with lim- hospitals and long-term care facilities (as
ited relevance to family physicians in the well as intravenous drug users), they were
Richard W. Sloan, United States; however, the problem is recently implicated as the cause of four
M.D., R.PH.,
coordinator of this
now increasing at an alarming rate in the pediatric deaths in the community over a
series, is chairman outpatient setting. In fact, various forms two-year period, raising concerns that this
and residency of antimicrobial resistance now pervade pathogen may spread to settings such as
program director all communities and all health care set- schools and day care facilities.1
of the Department tings, including the physician’s office and National medical organizations, in-
of Family Medicine at
York (Pa.) Hospital and
the home care environment. As a result, cluding the Infectious Diseases Society of
clinical associate pro- family physicians are confronted with America (IDSA), have identified antibi-
fessor in family and new diagnostic challenges, complicated otic resistance as a major concern. As the
community therapeutic choices, rising treatment problem worsens, physicians must evalu-
medicine at the costs and an increased risk of patient ate the ways in which they may be con-
Milton S. Hershey
Medical Center,
tributing to antibiotic resistance and ways
Pennsylvania State See editorial on page 1034. in which changes in their prescribing pat-
University, Hershey, Pa. terns can help manage it. Physicians have
MARCH 15, 2001 / VOLUME 63, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1087
when physicians know that the use of antibi-
Of all antibiotic prescriptions given in community settings, otics has marginal, if any, efficacy in particular
circumstances (e.g., viral infections), antibi-
20 percent to 50 percent are believed to be unnecessary.
otics may be prescribed so that physicians can
maintain good relationships with their
patients; these physicians are frequently torn
recognized the disturbing trends in resistance between scientific evidence and requests from
and are beginning to discuss solutions in their patients (Table 2).2
meetings such as the Summit on Antimicro- One recent study6 of parents found that
bial Resistance, sponsored by the Alliance for they would be satisfied with a medical visit
the Prudent Use of Antibiotics (APUA), which even if antibiotics were not prescribed, pro-
was convened in San Francisco before the vided the physician explained why this deci-
Interscience Conference on Antimicrobial sion was made. But a survey of primary care
Agents and Chemotherapy (ICAAC) in Sep- physicians in Massachusetts, conducted by
tember 1999. APUA in collaboration with the Massachu-
setts Department of Public Health and the
Scope of the Problem Massachusetts Infectious Diseases Society,
Millions of times each year physicians, found that the most common factors leading
regardless of specialty, prescribe antibiotics to increased antibiotic prescribing in outpa-
inappropriately. From 20 percent to 50 percent tient settings are patient requests for these
of antibiotic prescriptions in community set- drugs and the physician’s diagnostic uncer-
tings are believed to be unnecessary (Table 1).2,3 tainty. In addition, when physicians were
One recent report4 attributed these prescribing asked why they often prescribe broad-spec-
patterns to unreasonable patient expectations trum antibiotics if a targeted-spectrum agent
or demands, inadequate time to explain to would be effective, they cited diagnostic and
patients (or parents) why antibiotics are treatment uncertainty as the primary reasons
unnecessary and misdiagnosis of nonbacterial (unpublished data from APUA, retrieved
infections. Another study5 found that even August 1998, from: http://www.apua.org).
TABLE 1
Estimated Annual Human Antibiotic Use in the United States
Uses considered
Site of use Amount necessary (%) Resistant pathogens
Adapted with permission from Harrison PF, Lederberg J, eds. Antimicrobial resistance: issues and options. Work-
shop Report. Forum on Emerging Infections, Division of Health Sciences Policy, Institute of Medicine. Washing-
ton, D.C.: National Academy Press, 1998:40-1, and U.S. Congress, Office of Technology Assessment. Impacts of
Antibiotic-Resistant Bacteria, OTA-H-629. Washington, D.C.: US Government Printing Office, September 1995.
1088 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 63, NUMBER 6 / MARCH 15, 2001
Antibiotic Resistance
TABLE 2
Factors Responsible for Inappropriate Antibiotic Use
Adapted with permission from Harrison PF, Lederberg J, eds. Antimicrobial resistance: issues and options.
Workshop report. Forum on Emerging Infections, Division of Health Sciences Policy, Institute of Medicine.
Washington, D.C.: National Academy Press, 1998:46.
Because of the overuse of antibiotics, lance data, the prevalence of S. pneumoniae not
organisms that were susceptible to a number susceptible to penicillin varied among geo-
of agents even 10 years ago are now much graphic regions and among hospitals within
more difficult to manage. In the multina- those regions. Overall, 25 percent of isolates
tional SENTRY antimicrobial resistance sur- were not susceptible to penicillin: 11.4 percent
veillance program, 1,047 respiratory tract iso- exhibited intermediate susceptibility and
lates of Streptococcus pneumoniae were 13.6 percent were resistant. The highest pro-
obtained and analyzed in 1997.7 The percent- portion of nonsusceptible S. pneumoniae was
ages of penicillin-intermediate strains and found in Tennessee (38.3 percent).8
strains resistant to penicillin were 28 percent In the SENTRY surveillance program,
and 16 percent, respectively, in the United 92 percent of community-acquired respiratory
States; among 31 centers in the United States tract isolates of Moraxella catarrhalis produced
and Canada where 19 or more isolates were beta lactamase compared with 34 percent
collected, the combined incidence of inter- of isolates of Haemophilus influenzae; this
mediate plus highly resistant strains ranged beta-lactamase production results in amoxi-
from 24 percent to 68 percent.7 cillin resistance.9 Some strains of three bacter-
The Centers for Disease Control and Pre- ial species—Enterococcus faecalis, Myco-
vention (CDC) maintains its own population- bacterium tuberculosis and Pseudomonas
based surveillance system for S. pneumoniae aeruginosa—are resistant to almost every
within its Active Bacterial Core Surveillance antibiotic now available.10
program. It collects information on the sus- The problem of resistance is complicated
ceptibility patterns of invasive strains of this by the widespread use of antibiotics in ani-
organism.8 In a recent report of 1997 surveil- mals, which has implications for the treat-
MARCH 15, 2001 / VOLUME 63, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1089
sentative of areas in which increased caution
Although antibiotics may be effective in the treatment of may be advisable in administering antimicro-
bial agents.
acute exacerbations of chronic bronchitis, antibiotic therapy
is not generally indicated for cases of acute uncomplicated RESPIRATORY TRACT INFECTIONS
bronchitis. Research has failed to document a prophy-
lactic or therapeutic benefit from antibiotic
therapy in viral upper respiratory tract infec-
ment of human illness. For example, in low tions. Nevertheless, one study13 concluded
dosages, these compounds are used as growth that office visits for colds, upper respiratory
enhancers in animal feed for cattle and poul- tract infections and bronchitis accounted for
try. Although the mechanism by which about 2 million antibiotic prescriptions in
antibiotics promote animal growth is not well 1992; 51 percent of patients with colds, 52
understood, more than 40 percent of antibi- percent with upper respiratory tract infec-
otics manufactured in the United States are tions and 66 percent with bronchitis received
used in animals, mostly in feed but also to antibiotic treatment. Another study14 found
treat or prevent infections.10 This type of use that 60 percent of patients with an uncompli-
creates the circumstances for selecting resis- cated common cold received a prescription
tant bacteria in animals that may, in turn, be for an antibiotic.
passed to the human population at large.10,11 In many cases of uncomplicated upper res-
A panel of World Health Organization con- piratory tract infection, patients have mild
sultants has recommended the gradual dis- sinusitis-like symptoms (e.g., facial pressure,
continuation of antibiotics as growth pro- colored nasal discharge) and believe they need
moters in animals.12 antibiotics. As a result, they ask physicians for
these drugs, although there is no real need for
Appropriate Prescribing them. In most such patients, symptoms
For many of the leading illnesses diagnosed resolve spontaneously in seven to 10 days,
by office-based physicians, prescribing pat- although symptomatic management with
terns must be adjusted to minimize antibiotic nasal decongestants, hydration and antipyret-
resistance. The following diseases commonly ics may be warranted. One recent study15 con-
treated in family practice settings are repre- cluded that antibiotics did not improve the
clinical course of maxillary sinusitis in
patients presenting to general practices and
that initial treatment could be limited to
The Authors symptomatic management. The increasing
THOMAS M. HOOTON, M.D., is professor in the department of medicine at the Uni-
problem of antibiotic-resistant Haemophilus
versity of Washington School of Medicine, Seattle. He is also medical director of the influenzae and S. pneumoniae has provided
Harborview Medical Center AIDS Clinic in Seattle. Dr. Hooton received a medical further support for avoiding inappropriate
degree at the University of Texas Southwestern Medical School, Dallas, and completed
a residency in preventive medicine at the Centers for Disease Control and Prevention,
antibiotic use in managing sinusitis.16
Atlanta, and in medicine at the University of Washington School of Medicine. Nevertheless, the use of antibiotics is indi-
STUART B. LEVY, M.D., is professor of molecular biology and microbiology, professor
cated in patients with bacterial sinusitis. Cri-
of medicine and director of the Center for Adaptation Genetics and Drug Resistance teria for identifying the presence of infectious
at Tufts University School of Medicine, Boston. He received a medical degree from the sinusitis have been developed that include
University of Pennsylvania School of Medicine, Philadelphia, and completed a resi-
dency in internal medicine at Mt. Sinai Hospital in New York City.
five independent predictors of this infection:
purulent nasal secretions, history of colored
Address correspondence to Thomas M. Hooton, M.D., and Stuart B. Levy, M.D., c/o
Alliance for the Prudent Use of Antibiotics, 75 Kneeland St., Boston MA 02111 (e-mail:
nasal discharge, maxillary toothache, abnor-
apua@opal.tufts.edu). Reprints are not available from the authors. mal transillumination and poor response to
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pressure promoting an increased proportion they are afebrile and free of notable ear pain
of infections caused by multidrug-resistant or signs of middle ear pus or inflammation.33
strains of S. pneumoniae.31
About 80 percent of cases of acute otitis UNCOMPLICATED URINARY TRACT INFECTIONS
media in children resolve in seven to 14 days Urinary tract infections account for about
without treatment and with observation 7 million physician visits each year and are
alone, compared with about 95 percent of among the most common problems for which
patients receiving antibiotic therapy.30 Thus, young women seek medical care.35 In a recent
antibiotics have a modest but significant study36 of the prevalence of antimicrobial
impact on this condition.32 One current set resistance associated with acute uncompli-
of guidelines states that “antimicrobials are cated cystitis in women who visited a health
indicated for treatment of acute otitis media; maintenance organization, resistance to
however, diagnosis requires documented trimethoprim and trimethoprim-sulfame-
middle ear effusion and signs or symptoms thoxazole increased from 9 percent in 1992 to
of acute local or systemic illness.”30 Accord- 18 percent in 1996 among Escherichia coli and
ing to the same guidelines, “uncomplicated from 8 percent to 16 percent among all isolates
[acute otitis media] may be treated with a combined. The prevalence of resistance to
five- to seven-day course of antimicrobials in ampicillin and cephalothin also rose signifi-
certain patients.”30 On the other hand, cantly, although resistance to nitrofurantoin
antibiotics are not indicated for the initial and ciprofloxacin remained low.36 In other
treatment of otitis media with effusion in the surveys of young women with acute cystitis, 11
absence of signs or symptoms of acute infec- percent to 18 percent of causative strains were
tion or for persistent effusion after the treat- resistant to trimethoprim-sulfamethoxazole,
ment of acute otitis media.29 and 28 to 33 percent were resistant to ampi-
When antibiotic therapy is used, high-dose cillin. Resistance to nitrofurantoin and fluoro-
amoxicillin (in a dosage of 80 to 90 mg per kg quinolones was very low in these surveys.37
per day) is the treatment of choice in most According to the current practice guidelines
communities. If pain, fever and an inflamed of IDSA, a three-day regimen of trimetho-
tympanic membrane persist, resistance may be prim-sulfamethoxazole is considered standard
present. In such a case, the use of a second-line therapy for acute uncomplicated cystitis.38
drug, such as high-dose amoxicillin–clavu- Alternatives to trimethoprim-sulfamethoxa-
lanate potassium (Augmentin), cefuroxime zole should be considered in areas where the
axetil (Ceftin) or intramuscular ceftriaxone prevalence of resistance is 10 percent to 20 per-
(Rocephin) should be considered.33 cent or more.38 In mild uncomplicated cystitis,
“Watchful waiting,” or the withholding of it is reasonable to use a targeted-spectrum
antibiotic therapy from all but the sickest agent, such as a seven-day course of nitrofu-
children, is popular in some European coun- rantoin (Macrodantin) or a single dose of fos-
tries as a way of managing acute otitis media fomycin (Monurol). A three-day regimen of a
in children older than two years. The propo- fluoroquinolone is also acceptable treatment
nents of this approach in Europe initially use for uncomplicated cystitis.
analgesics for symptomatic management and To control costs and curtail antibiotic resis-
prescribe antibiotics only when signs or tance, however, IDSA recommends that fluo-
symptoms persist after observation for one to roquinolones not be used universally as first-
three days.33,34 In the United States, a review line agents for acute uncomplicated cystitis
article of recent consensus reports concluded but considered only in areas with high levels
that physicians could consider observation of resistance to trimethoprim-sulfamethoxa-
alone for children older than two years when zole.38 Increasing concerns over resistance
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more realistic through education. When given
Prescription Pad accurate information, patients tend to be sat-
isfied when reassured that symptomatic treat-
ment alone is appropriate in their case.
Name: ____________________________________ Date: ________________ • Before using antibiotics, make use of
diagnostic methods, when appropriate, to
Diagnosis: ■ Cold or flu ■ Middle ear fluid (otitis media with effusion) identify the causative pathogen so that a drug
■ Cough ■ Viral sore throat targeted at the microbe can be chosen.39
■ Other: • To help preserve the normal susceptible
flora in patients and slow the build-up of
antibiotic resistance in patients and in the
You have been diagnosed as having an illness caused by a
community, select targeted-spectrum antibi-
virus. Antibiotic treatment does not cure viral infections. If
given when not needed, antibiotics can be harmful. The otics when appropriate.10
treatments prescribed below will help you feel better while • Do not prescribe antibiotics for viral
your body’s own defenses are defeating the virus. infections, including the common cold.41,42 In
the management of otitis media, amoxicillin
General instructions:
should remain the agent of choice.33,43
■ Increase fluids.
• Recognize the importance of relieving
■ Use cool mist vaporizer or saline nasal spray to relieve symptoms experienced by patients. When
congestion.
appropriate, prescribe decongestants, cough
■ Soothe throat with ice chips or sore throat spray; lozenges medicine or antipyretics. The patients will be
for older children and adults.
appreciative and perhaps less demanding of
Specific medicines: antibiotics. The CDC has developed “pre-
■ Fever or aches: _____________________________________ scription pads” that help physicians explain to
their patients why an antibiotic is not being
■ Congestion: ________________________________________
prescribed and recommend symptomatic
■ Cough: ____________________________________________
treatments (Figure 1).44,45
■ Ear pain: ___________________________________________ • Make sure patients understand that, when
■ ________________ : ________________________________ they are prescribed an antibiotic, they must
■ ________________ : ________________________________ complete the full course of therapy even after
Use medicines as directed by your doctor or the package their symptoms have resolved to ensure that
instructions. Stop the medicine when the symptoms get better. all pathogenic bacteria are destroyed.42
Patients should be instructed not to keep left-
Follow-up:
over antibiotics in the medicine cabinet for
■ If not improved in _____ days, if new symptoms occur or if future use by family members.
you have other concerns, please call or return to the office
for a recheck.
• Use shorter courses of antibiotics when
supported by clinical data.
■ Other: _____________________________________________
• Adopt optimal hygiene practices and en-
courage your patients to do the same to
Signed: _______________________________________________ reduce infection risks. Washing hands thor-
oughly with soap and water between patient
visits is one of the best defenses against the
FIGURE 1. This “prescription pad” may be used to explain to patients
spread of antibiotic resistance.10,43 Waterless
why it is necessary for physicians to be cautious when prescribing hand-cleaning products, now used by person-
antibiotics. nel in many hospitals, are another increas-
Reprinted from Centers for Disease Control and Prevention, retrieved from: http:// ingly popular hygienic option.
www.cdc.gov/ncidod/antibioticresistance/files/viralprescriptionpad.pdf. • Remain abreast of the latest available data
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Antibiotic Resistance
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Final Comment
Haemophilus influenzae and Moraxella catarrhalis
Although managing antibiotic resistance is from patients with community-acquired respiratory
a major challenge, family physicians have an tract infections: antimicrobial susceptibility pat-
terns from the SENTRY Antimicrobial Surveillance
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