The new england journal of medicine
health policy report
Infection Control — A Problem for Patient Safety
John P. Burke, M.D.
Nosocomial, or hospital-acquired, infections (more
appropriately called health care–associated infec-
tions) are today by far the most common complica-
tions affecting hospitalized patients. Indeed, the
Harvard Medical Practice Study II found that a sin-
gle type of nosocomial infection — surgical-wound
infection — constituted the second-largest catego-
ry of adverse events.1 Long considered the greatest
risk that the hospital environment poses to pa-
tients,2 nosocomial infections abruptly became the
province of public health officers at the time of a
nationwide epidemic of hospital-based staphylo-
coccal infections, in 1957 and 1958.3 Since then, the
study and control of nosocomial infections have
been profoundly shaped by the discipline of pub-
lic health, with its emphasis on surveillance and
epidemiologic methods. These infections are not
only the most common types of adverse events in
health care; they may also be the most studied.
Currently, between 5 and 10 percent of patients
admitted to acute care hospitals acquire one or more
infections, and the risks have steadily increased dur-
ing recent decades (Table 1).4,5 These adverse events
affect approximately 2 million patients each year in
the United States, result in some 90,000 deaths, and
Table 1. Nosocomial Infections in the United States.*
Variable Year
1975
No. of admissions (¬10¡6) 37.7
No. of patient-days (¬10¡6) 299.0
Average length of stay (days) 7.9
No. of inpatient surgical proce- 18.3
dures (¬10¡6)
No. of nosocomial infections 2.1
(¬10¡6)
Incidence of nosocomial infections 7.2
(no. per 1000 patient-days)
*Data are from Weinstein4 and Jarvis.5
n engl j med 348;7
add an estimated $4.5 to $5.7 billion per year to the
costs of patient care.6,7 Infection control is therefore
a critical component of patient safety. In this article
I describe the common ground shared by these two
disciplines. I also discuss the major problems in in-
fection control, approaches to their solutions, the
role of the National Nosocomial Infections Surveil-
lance (NNIS) System of the Centers for Disease Con-
trol and Prevention (CDC) as a model, and the need
for renewed commitment to and innovations in in-
fection control to help ensure patient safety.
the nature of nosocomial
infections
Four types of infection account for more than 80
percent of all nosocomial infections: urinary tract
infection (usually catheter-associated), surgical-site
infection, bloodstream infection (usually associat-
ed with the use of an intravascular device), and pneu-
monia (usually ventilator-associated) (Fig. 1).8,9
One fourth of nosocomial infections involve pa-
tients in intensive care units, and nearly 70 percent
are due to microorganisms that are resistant to one
or more antibiotics — an emerging public health
crisis that is due in large part to indiscriminate use
of antibiotics.10
Nosocomial infections can also be ranked accord-
ing to their frequencies, associated mortality rates,
costs, and relative changes in frequency in recent
1995
years.4,7 Catheter-associated urinary tract infections
are the most frequent (accounting for about 35 per-
35.9
cent of nosocomial infections) but carry the lowest
190.0 mortality and lowest cost. Surgical-site infections
5.3 are second in frequency (about 20 percent) and third
in cost. Bloodstream infections and pneumonia are
13.3
less common (about 15 percent each) but are asso-
ciated with much higher mortality and costs. Blood-
1.9
stream infections and methicillin-resistant Staphy-
lococcus aureus infections share notoriety for being
9.8
both the highest-cost infections and the most rap-
idly increasing in frequency; the current incidence
of bloodstream infections is nearly three times the
incidence in 1975.4,11 The rates of both urinary tract
www.nejm.org february 13, 2003 651
 The new england journal of medicine

ventions to reduce the risk of infection. For exam-

40,000 ple, avoiding the use of invasive devices altogether
by means of alternative strategies (for example, per-
35,000
forming urinary drainage by condom catheter) and
Nosocomial Pathogens (no. of isolates)

30,000
25,000
20,000
15,000
10,000
5,000
0
Urinary Surgical- Bloodstream Pneumonia Other
Tract Site Infection Sites
Infection Infection
Figure 1. Number of Nosocomial Pathogens, According to Infection Site,
Identified in the Hospital-Wide Component of the National Nosocomial Infec-
tions Surveillance System from January 1990 to March 1996.
The hospital-wide component of the National Nosocomial Infections Surveil-
lance System consists of a subgroup of hospitals reporting data on nosoco-
mial infections from all patients. In January 1999, this component was
eliminated from the system.
and surgical-site infections have declined slightly,
perhaps because of surveillance artifacts caused by
decreases in the length of hospital stays and increas-
ing numbers of infections that develop after dis-
charge from the hospital.
Each of the main types of infection comprises
more than one syndrome and has multiple patho-
genetic pathways. For example, ventilator-associ-
ated pneumonia, a cause of one fourth of the deaths
attributed to nosocomial infections, commonly oc-
curs as a result of infection with one or more bacte-
rial species, but it may also occur with less common
pathogens, such as legionella, respiratory viruses,
or Aspergillus fumigatus.12 For each of the device-asso-
ciated infections, multiple risk factors are related to
the patient, the personnel caring for the patient, the
procedures they use, and the device itself.
prevention of
nosocomial infections
Identification of risk factors permits elucidation
of those that are alterable from those that are not
and facilitates the development of targeted inter-
shortening the duration of use of the device (for ex-
ample, reducing the number of days of mechanical
ventilation) have been proposed in many guidelines.
Strategies to prevent infections have been subdi-
vided into several groups (education-based, proc-
ess-based, and systems-based),13 but many of the
suggested interventions — such as “use antibiotics
wisely” or “educate and train staff”12 — have been
vague and difficult to implement.
Behavioral change remains a formidable ob-
stacle. For example, cross-infection of patients by
health care workers with contaminated hands is a
major source of infections. Despite educational ef-
forts, health care workers, including physicians,
continue to fail to adhere to standards for hand hy-
giene, which is universally considered the single
most important method for infection control. The
average level of compliance has varied among hos-
pitals from 16 percent to 81 percent.14 Barriers to
compliance include understaffing and poor design
of facilities, confusing and impractical guidelines
and policies, failure to apply behavioral-change the-
ory fully, and insufficient commitment and enforce-
ment by infection-control personnel.14,15 Remark-
ably, the use of waterless antiseptic hand rubs, when
part of a multifaceted campaign that encourages
appropriate hand washing, has been shown to be
more practical than standard hand washing alone
and has been shown to improve the adherence of
health care workers to hand-hygiene guidelines and
to prevent the transmission of methicillin-resistant
S. aureus to patients.16
The new Guideline for Hand Hygiene in Health-
Care Settings, developed by a multidisciplinary
task force,17 may facilitate system improvements
by resolving many inconsistencies among previous
guidelines from the CDC and other groups. It also
includes a requirement for monitoring adherence
to the guideline, along with suggested methods for
doing so. The guideline bans the use of artificial
nails when providing patient care, defines the dif-
ferent indications for hand washing as opposed to
decontamination, and calls for the use of alcohol-
based, waterless antiseptics for decontaminating
the hands before and after any direct contact with a
patient’s intact skin.
The history of infection control is littered with
commercial products and devices to prevent infec-

652 n engl j med 348;7 www.nejm.org february 13, 2003

 health policy report
tion that were widely promoted after limited test-
ing and have since been discredited.18 The devel-
opment of safer devices (for example, needles with
safety features and antimicrobial-coated catheters)
has produced incremental gains in infection con-
trol, but devices constructed of biomaterials that
fully prevent infections remain a tantalizing pros-
pect. Conversely, the actual infection-control bene-
fits of many technological improvements that were
not designed primarily to prevent infections, such
as improvements in anesthesia equipment and prac-
tice,19 are inestimable but probably great.
Because of the limitations of infection-control
methods, the fundamentals of prevention have nec-
essarily been grounded in epidemiology through the
development of standard definitions and classifi-
cations; surveillance and early reporting of infec-
tions, with feedback to “those who need to know”
(i.e., responsible authorities); evaluation of risk-
based interventions; and production of evidence-
based guidelines.20 This process has been guided by
the CDC, with the help of the American Hospital
Association and the regulatory efforts of the Joint
Commission on Accreditation of Healthcare Or-
ganizations.
Epidemiologic analysis, often by means of case–
control studies, is a powerful tool for identifying
the cause or source of nosocomial infections. One
example among hundreds is the recognition of a
hospital outbreak in which 11 cases of neonatal
sepsis over a period of four years were traced to a
single human carrier.21 Root-cause analysis of in-
dividual cases would have been incapable of identi-
fying the source of these or most other hospital in-
fections. Another example is the recognition of
erroneous handling of closed urinary-drainage sys-
tems as a cause of catheter-associated urinary tract
infections.22 In this analysis, too, there was epide-
miologic evidence of the importance of errors, even
though most of the errors were not followed by in-
fection. Moreover, voluntary reporting of frequently
occurring infections has been found to underesti-
mate greatly the true rate of avoidable infections, be-
cause most infections are considered unfortunate,
inevitable consequences of medical procedures.
Active surveillance is necessary to identify alter-
able risk factors (sometimes called process indica-
tors). Various indicators for infection control have
been extensively evaluated, for example, in the devel-
opment of a collaborative project to monitor health
care processes and outcomes.23 The growing im-
portance of monitoring process indicators is a be-
n engl j med 348;7 www.nejm.org
lated but major trend in infection control, but one
that does not diminish the need for surveillance of
outcomes. Without surveillance, we will not know
the effect of our efforts to prevent infection. Two
examples illustrate the value and limitations of proc-
ess indicators and the need for continued surveil-
lance: surgical-site infections and outbreaks in
hospitals.
surgical-site infections
Many quality-improvement projects have identi-
fied errors in the administration of antibiotic pro-
phylaxis before surgery as an independent risk fac-
tor for some postoperative infections. Incorrect
timing of surgical prophylaxis is associated with
increases by a factor of two to six in the rates of
surgical-site infection for operative procedures in
which prophylaxis is generally recommended.24
Failure to administer the first dose of antibiotic
within the two-hour window before incision (to
achieve adequate blood levels of the antibiotic dur-
ing surgery) remains a common error, occurring,
for example, in 27 to 54 percent of all selected op-
erations in a 1996 New York State study.25 Effec-
tive programs have recognized and addressed the
root causes of errors that result from faulty systems
of care.26 In most patients who receive inappropri-
ate prophylaxis, however, infections do not devel-
op, and therefore relatively stable (and seemingly
low) rates of surgical-site infections in an individual
hospital can mask the problem and create compla-
cency. Therefore, some limited monitoring of proc-
ess indicators, such as timely prophylaxis, is nec-
essary to detect system problems.
Improving the timing of antibiotic prophylaxis
does not supersede other elements of infection con-
trol. In several early studies, surveillance of surgi-
cal-site infections with confidential feedback of the
relevant data to surgeons was found to reduce the
risk of infection.27 Regardless of the reasons for
these results, the reasons for surveillance are no less
pressing today and have additional justifications,
with the use of ever more complex surgical proce-
dures and with the development of most postop-
erative infections after discharge from the hospi-
tal. Voluntary reporting of wound infections by
surgeons has not worked, and effective surveillance
requires active identification of cases by trained per-
sonnel and consideration of the use of automated
detection systems.28 The downsizing of many in-
fection-control programs due to hospitals’ financial
constraints29 has further increased the need for
february 13, 2003 653
 The new england journal of medicine

new types of surveillance and process indicators to of infections and to improve the use of isolation and
identify surgical-site infections. barrier precautions for infection control.35 Also
called “signals” or “alerts,” clinical triggers are ele-
outbreaks in hospitals ments drawn from patients’ electronic medical rec-
At least 5 to 10 percent of infections occur in clus- ords by means of programmed logic or algorithms
ters, or outbreaks, that can be detected from care- that suggest ongoing or potential adverse events,
ful review of surveillance information.30 Many out- including infections. Continuous, real-time scan-
breaks are recognized only by astute clinicians or ning of laboratory and pharmacy records, for ex-
laboratory workers. Most, if not all, infections in ample, facilitates cost-effective surveillance and ac-
outbreaks can be construed as accidental injuries. tive interventions to prevent or ameliorate adverse
Therefore, the detection, investigation, and control events. The LDS Hospital team monitored drug
of outbreaks are a critical issue in patient safety and doses, renal function, the prescription of common
require vigilance. antidotes, and other triggers to track and prevent
Though occasionally dramatic, outbreaks may adverse drug events.36 Interventions by a clinical
be insidious and may be protracted causes of sub- pharmacist reduced the use and misuse of antibiot-
stantial morbidity and mortality.21,31 They occur in ics and showed that the potential to stabilize anti-
all health care settings and with all classes of infec- biotic resistance existed.37 Voluntary reporting of
tious agents, especially antibiotic-resistant bacteria, medication errors had little overlap with adverse
and because of their sometimes widespread nature, drug events detected by this method. These concepts
often have a considerable effect on the public. Of are now being widely adopted by hospitals across
114 health care–associated outbreaks investigated the country through collaborative efforts coordi-
by CDC personnel over a 10-year period, 6 were na- nated by the Institute for Healthcare Improvement.
tional in scope and were traced to contaminated Recently, the Agency for Healthcare Research
products or devices.32 Contamination of commer- and Quality released a controversial report that re-
cially distributed products may be detected only by viewed the evidence in favor of 79 patient-safety
spontaneous reporting from infection-control units practices, of which 22 (28 percent) involved infec-
in hospitals. tion control.38 Further illustrating the common
Recently, data-mining tools have been applied ground shared by these two disciplines, 5 of the 11
to detect previously unrecognized outbreaks.33 practices that were judged worthy of widespread
Molecular techniques have been used to show that implementation involved infection control. Two of
seemingly unrelated infections have been caused these five practices — the appropriate use of antibi-
by interspecies transfer of genes encoding antibiot- otic prophylaxis in surgical patients and the use of
ic resistance, suggesting that the true rate of cross- maximal sterile barriers during the placement of
infection in hospital settings remains greatly un- central venous catheters — were readily accepted.
derestimated.34 These data indicate that the role of Curiously, the Agency for Healthcare Research and
laboratory-based surveillance in public health is Quality reported that there was weaker evidence
likely to increase. supporting methods to improve adherence to hand
hygiene and limitations in antibiotic use — practic-
the patient-safety movement es that some infection-control experts believe offer
the greatest potential benefit. These and other in-
The importance of the patient-safety movement in fection-control practices were listed as priorities
energizing infection control is already manifest. for further research.
Many infection-control units have broadened their
activities in monitoring the use of antibiotics and
is the nnis system a model
in preventing adverse drug events due to antibiot- for infection-control programs?
ics. (Antibiotic resistance may even be considered
a special type of adverse drug event, one with soci- The NNIS System of the CDC is a voluntary,
etal consequences.) confidential, hospital-based reporting system that
More than 25 years ago, the Department of Clin- has been influential in guiding infection-control
ical Epidemiology and Infectious Diseases of the efforts in hospitals across the United States and
LDS Hospital, in Salt Lake City, devised “clinical around the world; it is the only national source of
triggers” to facilitate the detection and surveillance systematically gathered data on hospital infections.

654 n engl j med 348;7 www.nejm.org february 13, 2003

 health policy report
Monthly reports of nosocomial infections from
more than 300 hospitals (a nonrandom sample of
U.S. hospitals, all with at least 100 beds and nearly
60 percent academic medical centers) have allowed
benchmarks for infection rates to be established
through the use of standardized case definitions
and data-collection methods and computerized
data entry and analysis.30 Analysis of NNIS System
data helps reveal changes in patterns of incidence,
distribution, antibiotic resistance, sites of infection,
outcomes, and risk factors for infection. In March
2000, the NNIS System reported that during the
1990s, the rates of infection for respiratory tract,
urinary tract, and bloodstream sites, after adjust-
ment for the duration of the use of invasive devices,
had decreased in intensive care units in selected hos-
pitals.39 The multiple reasons for these reductions,
however, cannot be attributed to any specific inter-
ventions, nor does the report mean that all hospi-
tals providing data to the NNIS System obtained
these salutary results, since only a subgroup of hos-
pitals participated.
The NNIS System is viewed as a benchmark on
the basis of the reasonable expectation that the par-
ticipating infection-control programs possess the
components for effectiveness identified by the CDC
in previous studies: intense surveillance, intense
control measures, and an adequate number of in-
fection-control professionals. Though not fully ad-
justed for patient risk factors, the rates of endemic
infections in participating hospitals have been used
to help drive improvement efforts. A few success
stories have been reported from selected hospitals
in which problems (such as excessive use of certain
invasive devices and deviations from national guide-
lines) were identified and addressed, but evaluation
is still incomplete.
Each hospital participating in the NNIS Sys-
tem provides data on only one or two high-risk com-
ponents of surveillance, such as intensive care or
selected surgical procedures. In addition, case ascer-
tainment is time-consuming and costly for hospi-
tals, and the definitions for infections are complex
and difficult to apply. Therefore, the NNIS System is
a model for focused surveillance but not for overall
infection control. This system has not yet addressed
many important safety issues, such as clinical errors
of omission leading to failures to diagnose infec-
tion or delays in the diagnosis of infection. Further-
more, the definitions used during surveillance (for
example, the definitions for ventilator-associated
n engl j med 348;7 www.nejm.org
pneumonia and for infections developing after hos-
pital discharge) are a work in progress.
Perhaps the most important outcome of the
NNIS System is the infrastructure of trained infec-
tion-control professionals that it has nurtured and
the cadre of CDC-trained infectious-disease physi-
cians who have migrated to university and commu-
nity hospitals during the past 30 years. These hu-
man resources are now endangered because of the
economic forces shaping health care and the down-
sizing of many, if not most, infection-control units
in hospitals. The voluntary nature of NNIS may be
an important factor in its success, but participation
also helps hospitals meet regulatory requirements.
In addition, the support of CDC epidemiologists is
a vital asset. More than a decade ago, the Institute
of Medicine called for further development of the
NNIS System and its expansion to include more U.S.
hospitals40; indeed, the system has grown rapidly,
from 120 hospitals in 1991 to more than 300 in
2001. The call for broader participation among all
U.S. hospitals is even more urgent today.
From the Department of Clinical Epidemiology and Infectious
Diseases, LDS Hospital; and the Department of Internal Medicine,
University of Utah School of Medicine — both in Salt Lake City.
1. Leape LL, Brennan TA, Laird N, et al. The nature of adverse
events in hospitalized patients: results of the Harvard Medical Prac-
tice Study II. N Engl J Med 1991;324:377-84.
2. Rothman KJ. Sleuthing in hospitals. N Engl J Med 1985;313:
258-60.
3. Langmuir AD. The Epidemic Intelligence Service of the Center
for Disease Control. Public Health Rep 1980;95:470-7.
4. Weinstein RA. Nosocomial infection update. Emerg Infect Dis
1998;4:416-20.
5. Jarvis WR. Infection control and changing health-care delivery
systems. Emerg Infect Dis 2001;7:170-3.
6. Public health focus: surveillance, prevention, and control of
nosocomial infections. MMWR Morb Mortal Wkly Rep 1992;41:
783-7.
7. Stone PW, Larson E, Kawar LN. A systematic audit of economic
evidence linking nosocomial infections and infection control inter-
ventions: 1990-2000. Am J Infect Control 2002;30:145-52.
8. Haley RW, Culver DH, White JW, Morgan WM, Emori TG. The
nationwide nosocomial infection rate: a new need for vital statistics.
Am J Epidemiol 1985;121:159-67.
9. National Nosocomial Infections Surveillance (NNIS) report,
data summary from October 1986–April 1996, issued May 1996: a
report from the National Nosocomial Infections Surveillance (NNIS)
system. Am J Infect Control 1996;24:380-8.
10. Eggimann P, Pittet D. Infection control in the ICU. Chest 2001;
120:2059-93.
11. Wenzel RP, Edmond MB. The impact of hospital-acquired
bloodstream infections. Emerg Infect Dis 2001;7:174-7.
12. Fleming CA, Steger KA, Craven DE. Host- and device-associated
risk factors for nosocomial pneumonia: cost-effective strategies for
prevention. In: Jarvis WR, ed. Nosocomial pneumonia. New York:
Marcel Dekker, 2000:53-92.
13. Olsen MA, Fraser VJ. Proving your value in healthcare epidemi-
ology and infection control. Semin Infect Control 2002;2:26-50.
february 13, 2003 655
 health policy report

14. Pittet D. Improving adherence to hand hygiene practice: a mul-
tidisciplinary approach. Emerg Infect Dis 2001;7:234-40.
15. Farr BM. Reasons for noncompliance with infection control
guidelines. Infect Control Hosp Epidemiol 2000;21:411-6.
16. Pittet D, Hugonnet S, Harbarth S, et al. Effectiveness of a hospi-
tal-wide programme to improve compliance with hand hygiene.
Lancet 2000;356:1307-12. [Erratum, Lancet 2000;356:2196.]
17. Boyce JM, Pittet D. Guideline for hand hygiene in health-care
settings: recommendations of the Healthcare Infection Control Prac-
tices Advisory Commmittee and the HICPAC/SHEA/APIC/IDSA
Hand Hygiene Task Force. MMWR Morb Mortal Wkly Rep 2002;
51(RR-16):1-45. (Also available at http://www.cdc.gov/ncidod/hip/
default.htm.)
18. Burke JP. Randomized controlled trials in hospital epidemiol-
ogy: sixth annual National Foundation for Infectious Diseases lec-
ture. Am J Infect Control 1983;11:165-73.
19. Hunt TK. Surgical wound infections: an overview. Am J Med
1981;70:712-8.
20. Scheckler WE, Brimhall D, Buck AS, et al. Requirements for
infrastructure and essential activities of infection control and epide-
miology in hospitals: a consensus panel report. Infect Control Hosp
Epidemiol 1998;19:114-24.
21. Burke JP, Ingall D, Klein JO, Gezon HM, Finland M. Proteus mira-
bilis infections in a hospital nursery traced to a human carrier.
N Engl J Med 1971;284:115-21.
22. Garibaldi RA, Burke JP, Dickman ML, Smith CB. Factors predis-
posing to bacteriuria during indwelling urethral catheterization.
N Engl J Med 1974;291:215-9.
23. Kritchevsky SB, Simmons BP, Braun BI. The Project to Monitor
Indicators: a collaborative effort between the Joint Commission on
Accreditation of Healthcare Organizations and the Society of
Healthcare Epidemiology of America. Infect Control Hosp Epide-
miol 1995;16:33-5.
24. Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL,
Burke JP. The timing of prophylactic administration of antibiotics
and the risk of surgical-wound infection. N Engl J Med 1992;326:
281-6.
25. Silver A, Eichorn A, Kral J, et al. Timeliness and use of antibiotic
prophylaxis in selected inpatient surgical procedures. Am J Surg
1996;171:548-52.
26. Burke JP. Maximizing appropriate antibiotic prophylaxis for
surgical patients: an update from LDS Hospital, Salt Lake City. Clin
Infect Dis 2001;33:Suppl 2:S78-S83.
27. Scheckler WE. Feedback of surgical-site infection rates to sur-
geons: recommendations, the data, and the current reality. Semin
Infect Control 2002;2:81-5.
28. Platt R. Progress in surgical-site infection surveillance. Infect
Control Hosp Epidemiol 2002;23:361-3.
29. Calfee DP, Farr BM. Infection control and cost control in the era
of managed care. Infect Control Hosp Epidemiol 2002;23:407-10.
30. Gaynes RP, Richards C, Edwards J, et al. Feeding back surveil-
lance data to prevent hospital-acquired infections. Emerg Infect Dis
2001;7:295-8.
31. Weinstein RA. Lessons from an epidemic, again. N Engl J Med
2001;344:1544-5.
32. Jarvis WR. Hospital Infections Program, Centers for Disease
Control and Prevention on-site outbreak investigations, 1990 to
1999. Semin Infect Control 2001;1:74-84.
33. Peterson LR, Brossette SE. Hunting health care-associated
infections from the clinical microbiology laboratory: passive, active,
and virtual surveillance. J Clin Microbiol 2002;40:1-4.
34. Leverstein-van Hall MA, Box ATA, Blok HEM, Paauw A, Fluit
AC, Verhoef J. Evidence of extensive interspecies transfer of inte-
gron-mediated antimicrobial resistance genes among multi-drug
resistant Enterobacteriaceae in a clinical setting. J Infect Dis 2002;
186:49-56.
35. Burke JP, Classen DC, Pestotnik SL, Evans RS, Stevens LE. The
HELP system and its application to infection control. J Hosp Infect
1991;18:Suppl A:424-31.
36. Classen DC, Pestotnik SL, Evans RS, Burke JP. Computerized
surveillance of adverse drug events in hospital patients. JAMA 1991;
266:2847-51. [Erratum, JAMA 1992;267:1922.]
37. Evans RS, Pestotnik SL, Classen DC, et al. A computer-assisted
management program for antibiotics and other antiinfective agents.
N Engl J Med 1998;338:232-8.
38. Making health care safer: a critical analysis of patient safety
practices. Evid Rep Technol Assess (Summ) 2001;43:1-668.
39. Monitoring hospital-acquired infections to promote patient
safety — United States, 1990–1999. MMWR Morb Mortal Wkly Rep
2000;49:149-53. [Erratum, MMWR Morb Mortal Wkly Rep 2000;
49:189-90.]
40. Lederberg J, Shope RE, Oaks SC Jr, eds. Emerging infections:
microbial threats to health in the United States. Washington, D.C.:
National Academy Press, 1992:121-2.
Copyright © 2003 Massachusetts Medical Society.

clinical problem-solving series

The Journal welcomes submissions of manuscripts for the Clinical Problem-Solving
series. This regular feature considers the step-by-step process of clinical decision
making. For more information, please see http://www.nejm.org/hfa/articles.asp.

656 n engl j med 348;7 www.nejm.org february 13, 2003