(Chest. 1999;115:34S-41S.)
© 1999
American College of Chest Physicians
Nosocomial Infections in the ICU*
The Growing Importance of Antibiotic-Resistant Pathogens
David J. Weber, MD, MPH;
Ralph Raasch, PharmD and
William A. Rutala, PhD, MPH
* From the Adult (Drs. Weber and Rutala) and Pediatric (Dr. Weber)
Infectious Disease Divisions, University of North Carolina School of Medicine;
the Department of Epidemiology (Dr. Weber), University of North Carolina
School of Public Health; the Department of Hospital Epidemiology (Drs. Weber
and Rutala), University of North Carolina Hospitals; and, the University of
North Carolina School of Pharmacy (Dr. Raasch), Chapel Hill, NC.
 |
Abstract
|
|---|
Patients hospitalized in ICUs are 5 to 10 times more likely to
acquire nosocomial infections than other hospital patients. The
frequency of infections at different anatomic sites and the risk of
infection vary by the type of ICU, and the frequency of specific
pathogens varies by infection site. Contributing to the seriousness of
nosocomial infections, especially in ICUs, is the increasing incidence
of infections caused by antibiotic-resistant pathogens. Prevention and
control strategies have focused on methicillin-resistant
Staphylococcus aureus, vancomycin-resistant Enterococcus,
and extended-spectrum ß-lactamase-producing Gram-negative bacilli,
among others. An effective infection control program includes a
surveillance system, proper handwashing, appropriate patient isolation,
prompt evaluation and intervention when an outbreak occurs, adherence
to standard guidelines on disinfection and sterilization, and an
occupational health program for health-care providers. Studies have
shown that patients infected with resistant strains of bacteria are
more likely than control patients to have received prior
antimicrobials, and hospital areas that have the highest prevalence of
resistance also have the highest rates of antibiotic use. For these
reasons, programs to prevent or control the development of resistant
organisms often focus on the overuse or inappropriate use of
antibiotics, for example, by restriction of widely used broad-spectrum
antibiotics (eg, third-generation cephalosporins) and
vancomycin. Other approaches are to rotate antibiotics used for empiric
therapy and use combinations of drugs from different
classes.
Key Words: antimicrobial resistance • broad-spectrum antibiotics • drug-resistant pathogens • nosocomial infections
|
Introduction
|
|---|
Since
the 1980s, infectious disease specialists have recognized that ICU
patients acquire nosocomial infections at a much higher rate than
patients elsewhere in the hospital. For ICU patients, the risk is as
much as 5 to 10 times greater than for those on general medical
wards.1
,2
,3
,4
This increased risk of nosocomial infection
results from three major factors: (1) intrinsic risk factors related to
the need for intensive care, such as severe underlying disease,
multiple illnesses, malnutrition, extremes of age, and
immunosuppression; (2) invasive medical devices, such as endotracheal
tubes for mechanical ventilation, intravascular catheters, and urinary
tract catheters; (3) crowding (eg, neonatal ICU) and animate
reservoirs (eg, colonized or infected patients), which
increase the risk of cross-infection in the ICU.
The most representative data on nosocomial infection rates have been
provided by the National Nosocomial Infections Surveillance (NNIS)
system.5
NNIS data indicate that today’s typical
hospitalized patient may be sicker than in former years. Data from
surveys of NNIS hospitals between 1988 and 1995 demonstrate a
significant increase in the number of ICU beds and a slight decrease,
not reaching statistical significance, in total beds.6
Surveillance data from ICUs are available for the years 1986 through
1997 (Table 1
).
7
Risk adjustment is provided by stratifying the data by
type of ICU and type of invasive medical device (ie,
ventilator, central venous catheter, urinary tract catheter) and by
presenting the infection rate as infections per 1,000 device days.
Further risk adjustment has been performed for infections in neonatal
ICUs by stratifying patients by birth weight.7
,8
From the NNIS data, one may conclude the following: the relative
frequency of different sites of nosocomial infections (ie,
ventilator-associated pneumonia, bloodstream infections, urinary tract
infections) and the absolute risk of infection (per 1,000 device days)
vary by type of ICU; the relative frequency of different nosocomial
pathogens varies by site of infection (Table 2
);
and the site-specific rates of nosocomial infections in similar types
of ICUs vary 10- to 20-fold among hospitals.7
View this table:
[in this window]
[in a new window]
|
Table 2. Distribution of the Five Most Common Nosocomial
Pathogens Isolated From the Four Major Infection Sites in the ICU,
January 1986–April 19977
|
|
|
Drug-Resistant Pathogens in the ICU
|
|---|
In the hospital, concern about drug-resistant pathogens has
focused on methicillin-resistant Staphylococcus aureus
(MRSA),9
,10
vancomycin-resistant Enterococcus sp
(VRE),11
,12
,13
extended-spectrum ß-lactamase-producing
Gram-negative bacilli,14
multidrug-resistant
Mycobacterium tuberculosis,15
fluconazole-resistant Candida sp,16
and most recently,
strains of S aureus with reduced susceptibility to
vancomycin—because such strains have now been isolated in Japan and
the United States.17
This concern has been fueled by
multiple reports of outbreaks of infection caused by these pathogens
and increasing rates of endemic infection in ICU patients. However,
only limited data are available regarding the prevalence of these
pathogens in ICUs throughout the United States. Data obtained from the
NNIS system documents the increasing frequency of VRE in US hospitals
(Fig 1 ).
17
,18
Archibald and colleagues6
reported the
prevalence of drug-resistant pathogens isolated from different patient
populations of eight hospitals between 1994 and 1995 (Table 3
).
For five of these antimicrobial/pathogen combinations, the percentage
of resistant isolates was significantly higher in the ICU than in the
two other settings.6
View this table:
[in this window]
[in a new window]
|
Table 3. Resistance to Specific Antimicrobials in Isolates
From Inpatients vs Outpatients for Sentinel Antimicrobial/Pathogen
Combinations*
|
|
|
Control of Nosocomial Infections in the ICU
|
|---|
Weinstein19
has summarized the traditional
infection-control measures used in ICUs (Table 4
).
Unfortunately, as noted by Weinstein, these control measures often fail
because frequently patients are already colonized with "nosocomial"
bacteria when hospitalized and because endogenous flora in ICU patients
is often amplified by antibiotics and gastric alkalization. Other
factors include selection by antibiotic pressure on
antibiotic-resistant bacterial subpopulations and spontaneous bacterial
resistance mutation, lapses in aseptic care during a crisis, spread on
hands of personnel caring for ventilator-dependent patients who have
heavy respiratory tract colonization or infection, unrecognized
environmental reservoirs, and new devices that break through anatomic
barriers.19
Key elements of an effective infection control program include a
surveillance system,20
proper hand washing before and
after contact with each patient or patient equipment,21
appropriate isolation of patients with transmissible pathogens, prompt
evaluation and intervention in cases of outbreaks,22
adherence to standard guidelines on disinfection and sterilization of
medical equipment,23
and an effective program of
occupational health focusing on preexposure and postexposure management
of health-care providers.24
Proper hand washing,
isolation, and disinfection are critical to prevent transmission of
resistant pathogens between patients via contaminated equipment or
contaminated hands of health-care providers. GI tract colonization of
health-care providers with resistant pathogens does not appear to be a
reservoir of these infectious agents.25
|
Prevention and Control of Antimicrobial Resistance
|
|---|
Consensus statements have been published recently that delineate
strategies to prevent and control the emergence and spread of
antimicrobial-resistant microorganisms in hospitals.26
,27
Prevention strategies are based on minimizing the transmission of
antibiotic-resistant pathogens between patients (Tables
5
and
6)
and developing a program to prevent or reduce antimicrobial resistance
(Table 7 ).
The Centers for Disease Control and Prevention (CDC) has published
general isolation guidelines to minimize the risk of transmission of
infectious agents from colonized/infected patients to other patients or
health-care providers.21
Detailed infection-control
recommendations have been published to minimize the transmission of
MRSA,28
VRE,18
and S aureus with
reduced susceptibility to vancomycin.17
View this table:
[in this window]
[in a new window]
|
Table 7. Elements of an Optimal Antimicrobial Control Program
to Study the Prevention or Reduction of Antimicrobial Resistance*
|
|
Consensus guidelines define an MRSA outbreak as "an increase in the
rate of MRSA cases or a clustering of new cases due to the transmission
of a single microbial strain in a health-care institution, including
long-term care facilities."28
The following threshold
rates (number of new nosocomial cases per 100 hospital
admissions/number of new nosocomial cases per 100 patient days) for
identifying high rates of MRSA transmissions are provided: < 200
hospital beds, 0.13/0.25; 200 to 499 hospital beds, 0.25/0.3; and, 
500 hospital beds, 0.5/0.6. A four-phase approach to control is
recommended (Table 5
).
The proper use of vancomycin (Table 6
)18
is especially
important because vancomycin use has risen dramatically in recent
years, and vancomycin use is one of the strongest risk factors for VRE
colonization/infection. The CDC guidelines for preventing the spread of
VRE include recommendations on the prudent use of vancomycin, an
educational program on VRE for hospital personnel, routine testing of
all enterococci isolated from blood and sterile body sites (except
urine) for vancomycin resistance, screening of all enterococcal
isolates for vancomycin resistance if VRE are detected, and appropriate
use of isolation precautions for all VRE-infected or colonized
patients.18
The focus on control of antimicrobial use stems from compelling
evidence of a causal association between antimicrobial use in hospitals
and resistance of pathogens to these antimicrobials.29
The
Society for Healthcare Epidemiology of America/Infectious Diseases
Society of America (SHEA/IDSA) guidelines point out the following:
changes in the use of antibiotics parallel changes in the prevalence of
resistance to them. Resistance is more prevalent in nosocomial
bacterial strains than in those from the community. Hospital patients
infected with resistant strains are more likely than control patients
to have received prior antimicrobials. Hospital areas that have the
highest prevalence of resistance also have the highest rates of use of
antibiotics. The longer a patient is exposed to antimicrobials, the
greater the likelihood of colonization with resistant
organisms.27
Risk Factors
Multiple case-control studies have analyzed the risk factors
associated with infection or colonization with MRSA or VRE. Both
univariate analysis in individual case studies and multivariate
analysis have demonstrated that antibiotic exposure30
,31
,32
,33
and cephalosporin use are risk factors for infection with
MRSA.33
,34
To prevent or control antimicrobial resistance, the SHEA/IDSA
guidelines propose the following: the selective removal, control, or
restriction of antimicrobial agents or classes; the rotation of
antimicrobial agents; and use of combination antimicrobial therapy. The
SHEA/IDSA guidelines also review specific methods to implement
antibiotic control policies (Table 8
).
The goal is to have all patients receive the most effective, least
toxic, and least costly antibiotic for the precise period needed to
cure or prevent an infection.27
Restriction of Antibiotic Use
By the early 1980s, most teaching hospitals had adopted
restriction policies for the use of selected expensive
agents.35
Himmelberg and colleagues36
demonstrated that institution of restriction policies was associated
with reduced antibiotic expenditures, but elimination of a restriction
policy resulted in an increase of 103% in the cost of the previously
restricted antibiotics.
In another study, implementation of a rigid protocol for the use of
preoperative prophylactic antibiotics resulted in cost savings of
57%.37
While antibiotic restriction policies clearly
result in lower cost, the influence of these programs on the prevalence
of resistance and on clinical outcomes has been less well defined.
Decreased use of broad-spectrum cephalosporins has been associated
temporally with decreased antibiotic resistance among Gram-negative
bacilli,38
,39
,40
,41
and decreased use of third-generation
cephalosporins and vancomycin has been associated with a decreased
incidence of VRE.42
Investigators have also found that
antibiotic control policies resulted in a stable median-length stay and
a reduction in the number of nosocomial infections treated with
antimicrobial drugs.37
White and colleagues43
evaluated the institution of a policy that required prior authorization
for selected parenteral antibiotics. Total parenteral antimicrobial
expenditures decreased by 32% and susceptibilities to all ß-lactam
and quinolone antibiotics increased. Importantly, for patients with
bacteremia caused by Gram-negative bacilli, the restrictions did not
change overall survival. Further, there were no differences in the
median time from positive blood culture to the prescription of an
appropriate antibiotic or in the median time to discharge from the
hospital. Evans and coworkers44
developed a computerized
decision-support program to assist physicians in the use of
anti-infective agents. Patients who received antibiotics recommended by
the computer program had significant reductions in the cost of
anti-infective agents, total hospital costs, and length of hospital
stay.
Substitution or rotation of antibiotics has been proposed as a method
for decreasing the prevalence of antibiotic-resistant pathogens.
Gerding et al45
reported that substitution of amikacin for
gentamicin led to a significant reduction in resistance to gentamicin
and tobramycin among Gram-negative bacilli. However, the first attempt
to reintroduce gentamicin led to a resurgence of gentamicin resistance.
Kollef and coworkers46
replaced ceftazidime with
ciprofloxacin for empiric therapy for ventilator-associated pneumonia
and demonstrated a reduction in the incidence of ventilator-associated
pneumonia attributed to antibiotic-resistant Gram-negative bacteria.
However, limitations with this study preclude accepting its conclusion
that a scheduled change of antibiotic classes can reduce the incidence
of ventilator-associated pneumonia. First, the incidence of pneumonia
declined for unclear reasons. Second, only a single change was
evaluated rather than multiple changes. Finally, the follow-up period
was only 6 months.
|
Conclusions
|
|---|
Nosocomial infections, especially those caused by
antibiotic-resistant pathogens, represent an important source of
morbidity and mortality for the patient hospitalized in an ICU.
Important antibiotic-resistant nosocomial pathogens include MRSA, VRE,
Gram-negative bacilli (especially, Klebsiella and Enterobacter)
producing extended-spectrum ß-lactamases, multiple drug-resistant
M tuberculosis, and fluconazole-resistant Candida sp.
The key to control of antibiotic-resistant pathogens in the ICU is
rigorous adherence to infection control guidelines and prevention of
antibiotic misuse. Antibiotic restriction policies clearly result in
reduced drug costs. Evidence suggests that reducing use of certain
antibiotics may lead to a decreased prevalence of antibiotic-resistant
pathogens: vancomycin, VRE; gentamicin, gentamicin-resistant
Gram-negative bacilli; and, ceftazidime, Gram-negative bacilli
producing extended-spectrum ß-lactamases. Limited data suggest that
measures to control antibiotic use do not adversely affect—and may
actually improve—patient outcomes (eg, decreased length of
stay, risk of subsequent infection).
Unfortunately, relatively few appropriately designed studies have
evaluated the impact of antibiotic- and infection-control interventions
on the prevalence of antibiotic resistance among nosocomial pathogens
and on patient outcomes. The efficacy of intensive antibiotic control
should be assessed in multicenter studies designed to avoid
methodologic flaws.47
Preventing the emergence of
multidrug-resistant microorganisms requires the adoption of a
multifaceted approach.48
|
Appendix 1
|
|---|
Dr. Weber: I just want to go over briefly the
nosocomial guidelines from the American Thoracic Society. These have a
complicated scheme based on risk factors, onset of disease, etc. One of
the weaknesses of the guidelines is that they just tell you to use a
quinolone or a ß-lactam/ß-lactamase inhibitor combination. I do not
think many of us would use ampicillin/sulbactam in the ICU for
nosocomial pneumonia, but that would meet the American Thoracic Society
guidelines. I have updated this and added specific drugs. I believe
that appropriate drugs would include piperacillin/tazobactam,
cefotaxime, ceftriaxone, and cefepime. If you have anaerobes, they
suggest adding clindamycin. If you are worried about that, you can use
piperacillin/tazobactam alone.
If the patient has severe pneumonia, then it is an aminoglycoside,
ciprofloxacin, or trovafloxacin plus one of the other drugs we just
mentioned. In the ICUs in general, people are going to pick one of the
combinations of piperacillin/tazobactam, ceftazidime, cefepime,
imipenem, or meropenem with ciprofloxacin, trovafloxacin, or an
aminoglycoside. I think that is going to be the standard therapy in
ICUs, plus or minus vancomycin, depending on MRSA.
So antibiotic resistance is a growing problem and control of antibiotic
use is crucial, but few guidelines can aid the clinician in what
interventions to use. There are very limited data demonstrating
effective control measures for outcomes other than cost. Most
guidelines and multiple studies suggest that vancomycin should be
limited, and that an increase in cephalosporin use increases the
likelihood of VRE and extended-spectrum ß-lactamase. Obviously
piperacillin/tazobactam is an excellent therapy for several common ICU
infections, such as pneumonia, and may have a reduced risk of
precipitating resistance.
Dr. Campbell: For prior authorization of an antibiotic, does
the prescribing physician call the infectious disease specialist to
ask, "May I use this drug?"
Dr. Weber: That is what we were doing up to about 8 years
ago. The prescribing physicians would have to call the infectious
diseases specialist, and then the infectious diseases specialist would
ask, "Why do you want to use that?"
Dr. Campbell: This may work in a university or Veterans
Affairs hospital, but once you try to move it into private
hospitals—you cannot do it.
Dr. Weber: I agree that it is particularly hard in the
private hospitals. Now we have moved away from prior authorization, and
pharmacy has a set of guidelines as to which antibiotics should be
used, depending on the clinical issues.
|
Footnotes
|
|---|
Correspondence to: David Jay Weber, MD, MPH, CB 7030
Burnett-Womack, 547, Division of Infectious Diseases, University of
North Carolina at Chapel Hill, Chapel Hill, NC 27599-7030
Abbreviations:
CDC = Centers for Disease Control and Prevention;
MRSA = methicillin-resistant Staphylococcus aureus;
NNIS = National Nosocomial Infections Surveillance;
SHEA/IDSA = Society for Healthcare Epidemiology of America/Infectious
Diseases Society of America; VRE = vancomycin-resistant Enterococcus
sp
|
References
|
|---|
- Donowitz, LG, Wenzel, RP, Hoyt, JW (1982) High risk of hospital-acquired infection in the ICU patient. Crit Care Med 10,355-357[ISI][Medline]
- Chandrasekar, PH, Kruse, JA, Matthews, MF (1986) Nosocomial infection among patients in different types of intensive care units at a city hospital. Crit Care Med 14,508-510[ISI][Medline]
- Brown, RB, Hosmer, D, Chen, HC, et al (1985) A comparison of infections in different ICUs within the same hospital. Crit Care Med 13,472-476[ISI][Medline]
- Brawley, RL, Weber, DJ, Samsa, GP, et al (1989) Multiple nosocomial infections: an incidence study. Am J Epidemiol 130,769-780[Abstract/Free Full Text]
- Emori, TG, Culver, DH, Horan, TC, et al (1991) National nosocomial infections surveillance system (NNIS): description of surveillance methods. Am J Infect Control 19,19-35[CrossRef][ISI][Medline]
- Archibald, L, Phillips, L, Monnet, D, et al (1997) Antimicrobial resistance in isolates from inpatients and outpatients in the United States: increasing importance of the intensive care unit. Clin Infect Dis 24,211-215[ISI][Medline]
- . National Nosocomial Infections Surveillance (NNIS) report (1997) Data summary from October 1986–April 1997, issued May 1997: a report from the NNIS System. Am J Infect Control 25,477-487[CrossRef][ISI][Medline]
- Gaynes, RP, Edwards, JR, Jarvis, WR, et al (1996) Nosocomial infections among neonates in high-risk nurseries in the United States. Pediatrics 98,357-361[Abstract/Free Full Text]
- Boyce, JM (1989) Methicillin-resistant Staphylococcus aureus: detection, epidemiology, and control measures. Infect Dis Clin North Am 3,901-913[Medline]
- Mulligan, ME, Standiford, HC, Kauffman, CA (1993) Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. Am J Med 94,313-328[CrossRef][ISI][Medline]
- Murray, BE (1997) Vancomycin-resistant enterococci. Am J Med 102,284-293[CrossRef][ISI][Medline]
- Eliopoulos, GM (1997) Vancomycin-resistant enterococci: mechanism and clinical relevance. Infect Dis Clin North Am 11,851-865[CrossRef][ISI][Medline]
- Boyce, JM (1997) Vancomycin-resistant enterococcus: detection, epidemiology, and control measures. Infect Dis Clin North Am 11,367-384[CrossRef][ISI][Medline]
- Paterson DL, Ko WC, Mohapatra S, et al. Klebsiella pneumoniae bacteremia: impact of extended spectrum beta-lactamase (ESBL) production in a global study of 216 patients [abstract]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept 28–Oct 1, 1997; Toronto, Ontario, Canada
- . CDC. (1994) Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities, 1994. MMWR 43(No. RR-13),1-132
- White, TC, Marr, KA, Bowden, RA (1998) Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 11,382-402[Abstract/Free Full Text]
- . CDC. (1997) Update: Staphylococcus aureus with reduced susceptibility to vancomycin—United States, 1997. MMWR 46,813-815[Medline]
- . CDC. (1994) Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR 44,1-13
- Weinstein, RA (1991) Epidemiology and control of nosocomial infections in adult intensive care units. Am J Med 91(suppl 3B),179S-184S[CrossRef][Medline]
- Perl, TM (1997) Surveillance, reporting, and the use of computers. Wenzel, RP eds. Prevention and control of nosocomial infections 3rd ed. ,127-161 Williams & Wilkins Baltimore, MD.
- Garner, JS (1996) Hospital Infection Control Practices Advisory Committee: guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol 17,53-80[Medline]
- Wendt, C, Herwaldt, LA (1997) Epidemics: identification and management. Wenzel, R eds. Prevention and control of nosocomial infections 3rd ed. ,175-213 Williams & Wilkins Baltimore, MD.
- Rutala, WA (1996) APIC guideline for selection and use of disinfectants. Am J Infect Control 24,313-342[ISI][Medline]
- Bolyard, EA, Tablan, OC, Williams, WW, et al (1998) Guideline for infection control in health care personnel, 1998. Am J Infect Control 26,289-354
- Carmeli, Y, Venkataraman, L, DeGirolami, PC, et al (1998) Stool colonization of healthcare workers with selected resistant bacteria. Infect Control Hosp Epidemiol 19,38-40[ISI][Medline]
- Goldmann, DA, Weinstein, RA, Wenzel, RP, et al (1996) Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals: a challenge to hospital leadership. JAMA 275,234-240[Abstract]
- Shlaes, DM, Gerding, DN, John, JF, Jr, et al (1997) Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals. Clin Infect Dis 25,584-599[ISI][Medline]
- Wenzel, RP, Reagan, DR, Bertino, JS, Jr, et al (1998) Methicillin-resistant Staphylococcus aureus outbreak: a consensus panel’s definition and management guidelines. Am J Infect Control 26,102-110[CrossRef][ISI][Medline]
- McGowan, JE (1983) Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 5,1033-1048[ISI][Medline]
- Law, MR, Gill, ON (1988) Hospital-acquired infection with methicillin-resistant and methicillin-sensitive staphylococci. Epidemiol Infect 101,623-629[Medline]
- Hershow, RC, Khayr, WF, Smith, NL (1992) A comparison of clinical virulence of nosocomially acquired methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections in a university hospital. Infect Control Hosp Epidemiol 13,587-593[ISI][Medline]
- Coll, PP, Crabtree, BF, O’Connor, PJ, et al (1994) Clinical risk factors for methicillin-resistant Staphylococcus aureus bacteriuria in a skilled-care nursing home. Arch Fam Med 3,357-360[Abstract]
- Washio, M, Mizoue, T, Kajioka, T, et al (1997) Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in a Japanese geriatric hospital. Public Health 111,187-190[CrossRef][ISI][Medline]
- Peacock, JE, Jr, Marsik, FJ, Wenzel, RP (1980) Methicillin-resistant Staphylococcus aureus: introduction and spread within a hospital. Ann Intern Med 93,526-532[ISI][Medline]
- Klapp, DL, Ramphal, R (1983) Antibiotic restriction in hospitals associated with medical schools. Am J Hosp Pharm 40,1957-1960[Abstract]
- Himmelberg, CJ, Pleasants, RA, Weber, DJ, et al (1991) Use of antimicrobial drugs in adults before and after removal of a restriction policy. Am J Hosp Pharm 48,1220-1227[Abstract]
- Gyssens, IC, Geerligs, IEJ, Dony, JMJ, et al (1996) Optimising antimicrobial drug use in surgery: an intervention study in a Dutch university hospital. J Antimicrob Chemother 38,1001-1012[Abstract/Free Full Text]
- Ballow, CH, Schentag, JJ (1992) Trends in antibiotic utilization and bacterial resistance: report of the National Nosocomial Resistance Surveillance Group. Diagn Microbiol Infect Dis 15,37S-42S[Medline]
- Bamberger, DM, Dahl, SL (1992) Impact of voluntary vs enforced compliance of third-generation cephalosporin use in a teaching hospital. Arch Intern Med 152,554-557[Abstract]
- Jones, RN (1992) The current and future impact of antimicrobial resistance among nosocomial bacterial pathogens. Diagn Microbiol Infect Dis 15,3S-10S[Medline]
- Meyer, KS, Urban, C, Eagan, JA, et al (1993) Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins. Ann Intern Med 119,353-358[Abstract/Free Full Text]
- Quale, J, Landman, D, Saurina, G, et al (1996) Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin Infect Dis 23,1020-1025[ISI][Medline]
- White, AC, Jr, Atmar, RL, Wilson, J, et al (1997) Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities, and clinical outcomes. Clin Infect Dis 25,230-239[ISI][Medline]
- Evans, RS, Pestotnik, SL, Classen, DC, et al (1998) A computer-assisted management program for antibiotics and other antiinfective agents. N Engl J Med 338,232-238[Abstract/Free Full Text]
- Gerding, DN, Larson, TA, Hughes, RA, et al (1991) Aminoglycoside resistance and aminoglycoside usage: 10 years of experience in one hospital. Antimicrob Agents Chemother 35,1284-1290[Abstract/Free Full Text]
- Kollef, MH, Vlasnik, J, Sharpless, L, et al (1997) Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 156,1040-1048[Abstract/Free Full Text]
- McGowan, JE, Jr (1994) Do intensive hospital antibiotic control programs prevent the spread of antibiotic resistance? Infect Control Hosp Epidemiol 15,478-483[ISI][Medline]
- Jarvis, WR (1996) Preventing the emergence of multidrug-resistant microorganisms through antimicrobial use controls: the complexity of the problem. Infect Control Hosp Epidemiol 17,490-495[ISI][Medline]
- . CDC. (1997) Summary of notifiable diseases, United States, 1996. MMWR 45,1-87[Medline]
This article has been cited by other articles:
|
|
|
|
 
A. Corona, A. P. R. Wilson, M. Grassi, and M. Singer
Prospective audit of bacteraemia management in a university hospital ICU using a general strategy of short-course monotherapy
J. Antimicrob. Chemother.,
October 1, 2004;
54(4):
809 - 817.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-L. Wu, P. Domenico, D. J. Hassett, T. J. Beveridge, A. R. Hauser, and J. A. Kazzaz
Subinhibitory Bismuth-Thiols Reduce Virulence of Pseudomonas aeruginosa
Am. J. Respir. Cell Mol. Biol.,
June 1, 2002;
26(6):
731 - 738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-S. Jean, L.-J. Teng, P.-R. Hsueh, S.-W. Ho, and K.-T. Luh
Antimicrobial susceptibilities among clinical isolates of extended-spectrum cephalosporin-resistant Gram-negative bacteria in a Taiwanese University Hospital
J. Antimicrob. Chemother.,
January 1, 2002;
49(1):
69 - 76.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-P. Choo-Smith, K. Maquelin, T. van Vreeswijk, H. A. Bruining, G. J. Puppels, N. A. N. Thi, C. Kirschner, D. Naumann, D. Ami, A. M. Villa, et al.
Investigating Microbial (Micro)colony Heterogeneity by Vibrational Spectroscopy
Appl. Envir. Microbiol.,
April 1, 2001;
67(4):
1461 - 1469.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. Singh and V. L. Yu
Rational Empiric Antibiotic Prescription in the ICU
Chest,
May 1, 2000;
117(5):
1496 - 1499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S G B Amyes
The rise in bacterial resistance
BMJ,
January 22, 2000;
320(7229):
199 - 200.
[Full Text]
|
|
|
TOP
Abstract
Introduction
