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Original Article |

Use of Antimicrobial Prophylaxis for Major Surgery:  Baseline Results From the National Surgical Infection Prevention Project FREE

Dale W. Bratzler, DO, MPH; Peter M. Houck, MD; Chesley Richards, MD, MPH; Lynn Steele, MS, CIC; E. Patchen Dellinger, MD; Donald E. Fry, MD; Claudia Wright, MS; Allen Ma, PhD; Karina Carr, RN; Lisa Red, MSHA
[+] Author Affiliations

Author Affiliations: Oklahoma Foundation for Medical Quality, Inc, Oklahoma City (Drs Bratzler and Ma and Mss Wright, Carr, and Red); Centers for Medicare [[amp]] Medicaid Services (CMS), Seattle, Wash (Dr Houck); Division of Healthcare Quality Promotion, National Center for Infectious Diseases (Dr Richards), and Office of the Director (Ms Steele), Centers for Disease Control and Prevention, Atlanta, Ga; and Departments of Surgery, University of Washington, Seattle (Dr Dellinger); and University of New Mexico, Albuquerque (Dr Fry).


Arch Surg. 2005;140(2):174-182. doi:10.1001/archsurg.140.2.174.
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Published online

Hypothesis  Surgical site infections (SSIs) are a major contributor to patient injury, mortality, and health care costs. Despite evidence of effectiveness of antimicrobials to prevent SSIs, previous studies have demonstrated inappropriate timing, selection, and excess duration of administration of antimicrobial prophylaxis. We herein describe the use of antimicrobial prophylaxis for Medicare patients undergoing major surgery.

Design  National retrospective cohort study with medical record review.

Setting  Two thousand nine hundred sixty-five acute-care US hospitals.

Patients  A systematic random sample of 34 133 Medicare inpatients undergoing coronary artery bypass grafting; other open-chest cardiac surgery (excluding transplantation); vascular surgery, including aneurysm repair, thromboendarterectomy, and vein bypass operations; general abdominal colorectal surgery; hip and knee total joint arthroplasty (excluding revision surgery); and abdominal and vaginal hysterectomy from January 1 through November 30, 2001.

Main Outcome Measures  The proportion of patients who had parenteral antimicrobial prophylaxis initiated within 1 hour before the surgical incision; the proportion of patients who were given a prophylactic antimicrobial agent that was consistent with currently published guidelines; and the proportion of patients whose antimicrobial prophylaxis was discontinued within 24 hours after surgery.

Results  An antimicrobial dose was administered to 55.7% (95% confidence interval [CI], 54.8%-56.6%) of patients within 1 hour before incision. Antimicrobial agents consistent with published guidelines were administered to 92.6% (95% CI, 92.3%-92.8%) of the patients. Antimicrobial prophylaxis was discontinued within 24 hours of surgery end time for only 40.7% (95% CI, 40.2%-41.2%) of patients.

Conclusion  Substantial opportunities exist to improve the use of prophylactic antimicrobials for patients undergoing major surgery.

Figures in this Article

Surgical site infections (SSIs) are a major contributor to patient injury, mortality, and health care costs. Of the nearly 30 million operations in the United States each year, more than 2% are complicated by an SSI.15 Mortality rates are 2 to 3 times higher in patients in whom an SSI develops compared with uninfected patients, and hospital readmission rates are significantly increased.68 Surgical site infections increase length of stay by an average of 7 days and charges by approximately $3000.6,9 When an SSI is diagnosed after hospital discharge, outpatient and emergency department visits, use of radiology services, hospital readmissions, and use of home health care services increase significantly, as do total health care costs.10 The attributable costs of an SSI may be more than $30 000 for patients undergoing cardiac or orthopedic operations.1114

The effectiveness of antimicrobials administered shortly before skin incision for prevention of SSIs was established in the 1960s and has been repeatedly demonstrated since.1521 However, despite evidence of effectiveness and the publication of guidelines for antimicrobial prophylaxis,2228 use is often suboptimal. Previous studies have demonstrated inappropriate timing of antimicrobial administration, inappropriate selection of the antimicrobial agent, and excess duration of prophylaxis.2934 In a 1996 study of patients undergoing abdominal aortic aneurysm repair, hip replacement, or large-bowel resection in 44 hospitals in New York State, Silver and colleagues30 demonstrated that 14% did not receive antimicrobial prophylaxis, and only 63% of those who received antimicrobials had them administered in the 2 hours before incision.

In 2002, the Centers for Medicare & Medicaid Services, in collaboration with the Centers for Disease Control and Prevention, implemented the National Surgical Infection Prevention Project. The project promotes prophylactic practices that have been shown to reduce the risk of SSI, and thus reduce morbidity and mortality in the Medicare population. This project builds on experience that the Centers for Disease Control and Prevention has gained from implementation of the National Nosocomial Infections Surveillance System3538 and on previous efforts by Centers for Medicare & Medicaid Services to improve health care quality through its Medicare quality improvement organizations.3941 This report describes baseline results of an assessment of use of antimicrobial prophylaxis for a national sample of Medicare patients undergoing 5 types of major surgery during 2001.

STUDY DESIGN

After a literature review, a panel of experts in surgical infection prevention, hospital infection control, and epidemiology developed 3 performance measures for national surveillance and quality improvement.42 These measures include (1) the proportion of patients in whom parenteral antimicrobial prophylaxis is initiated within 1 hour before the incision (2 hours for vancomycin hydrochloride); (2) the proportion of patients who are given a prophylactic antimicrobial regimen consistent with published guidelines2226,28; and (3) the proportion of patients whose antimicrobial prophylaxis is discontinued within 24 hours after the end of surgery. Timing and selection of antimicrobial prophylaxis were selected as measures because of the association with reduced SSI incidence. Duration was selected because excessive use of antimicrobials promotes bacterial resistance. Operations were selected for inclusion in the project based on frequency in the Medicare population, rate of postoperative SSI, and consensus regarding appropriate antimicrobial prophylaxis. Informed consent and institutional review board approval were not required because access to these data for quality assurance is given to the Medicare program by statute.

PATIENT POPULATION

The study population included Medicare fee-for-service beneficiaries from all states or territories except the Virgin Islands who underwent selected operations from January 1 through November 30, 2001. A case was defined by a Medicare part A claim with a principal or secondary procedure code from the International Classification of Diseases, Ninth Revision, Clinical Modification,43 for coronary artery bypass grafting (36.10-36.17, 36.19, and 36.2), open-chest cardiac surgery (35.0-35.51, 35.53-35.95, 35.98, and 35.99), colon surgery (45.00, 45.03, 45.41, 45.49, 45.50, 45.7-45.90, 45.92-45.95, 46.03, 46.04, 46.1-46.14, 46.52, 46.75, 46.76, 46.91, 46.92, 46.94, 48.5, and 48.6-48.69), hip or knee arthroplasty (81.51, 81.52, and 81.54), abdominal or vaginal hysterectomy (68.3, 68.4, and 68.5-68.7), or vascular surgery (38.14, 38.16, 38.18, 38.34, 38.36, 38.37, 38.44, 38.48, 38.49, 38.51, 38.52, 38.64, 39.25, 39.26, and 39.29).42 A systematic random sample of 788 cases was selected for each state or territory to give approximately 750 usable records after allowing for exclusions and unavailable charts. In states with fewer than 750 eligible medical charts based on the selected operations, all available discharges were reviewed.

DATA COLLECTION

Hospitals sent photocopies of medical records to 1 of 2 clinical data abstraction centers. Abstractors used computerized tools with explicit predefined criteria to record data elements, including patient demographics, diagnosis and procedure codes, antimicrobial use before surgery, documented antimicrobial allergies, presence of any preoperative infection, operating room arrival time, anesthesia start time, surgical incision time or surgery start time, and surgery end time. Detailed information on route, administration time of all doses, and time of discontinuation were collected for each course of antimicrobial prophylaxis administered during the hospitalization. Data on postoperative complications, including infections during the hospitalization, were collected if documented in the medical chart.

DATA RELIABILITY

A subset of 559 cases was randomly selected for an independent review by a second abstractor. The κ statistics for the 3 performance measures included 0.76 for antimicrobials received within 1 hour before incision, 0.91 for antimicrobial selection consistent with published guidelines, and 0.86 for antimicrobial prophylaxis discontinued within 24 hours after the end of surgery, indicating high interabstractor agreement.

DATA ANALYSIS

Cases were excluded from analysis if results of the medical chart review did not confirm that 1 of the operations of interest was performed or if there were missing dates or times that prevented evaluation of antimicrobial administration timing. Because the project focuses on prophylactic antimicrobial use, cases with documented preoperative infection, preadmission antimicrobial administration (except for oral antimicrobial prophylaxis for colon surgery), or more than 24 hours of preoperative antimicrobial administration were excluded.

The proportion of patients receiving antimicrobial prophylaxis within 60 minutes (120 minutes for vancomycin) before incision was determined by comparing the start time of the last parenteral antimicrobial dose before the surgical incision with the documented incision time. Cases without an explicitly documented incision time were excluded from this measure. We also excluded cases with insufficient timing data or if a patient undergoing colon surgery received oral antimicrobial prophylaxis only.

The proportion of patients receiving antimicrobial drugs consistent with published guidelines was calculated by evaluating whether the patient received any antimicrobial or combination of antimicrobials consistent with any of the guidelines.42 Antimicrobials were considered prophylactic if given before surgery, intraoperatively, or within 24 hours of the end of surgery. Cases were excluded from this measure if no antimicrobials were administered or if no antimicrobials were considered prophylactic. Because there were no guidelines for antimicrobial selection in patients with a β-lactam allergy undergoing colon surgery or hysterectomy, these patients were excluded from this measure.

The proportion of patients whose antimicrobial prophylaxis was discontinued within 24 hours after the end of surgery was calculated by comparing the start time of the last dose of prophylactic antimicrobial with the surgery end time. Cases were excluded from this measure if any infection was documented intraoperatively or within 48 hours after the end of surgery. In addition, cases were excluded if no antimicrobials were administered, if no antimicrobials were considered prophylactic, if there were insufficient data to determine antimicrobial timing, or if the patient underwent more than 1 operation of interest during the hospitalization.

Because the sample of cases represented a fixed maximum number of patients per state, we applied normalized weights to adjust all performance measures. We calculated exact binomial 95% confidence intervals (CIs) for unweighted and weighted performance measure rates. All analyses were completed using SAS statistical software (SAS version 8.2; SAS Institute Inc, Cary, NC).

We abstracted data from a total of 39 086 medical records and applied general exclusions sequentially. Excluded cases included 205 (0.5%) with no surgery of interest performed, 1817 (4.7%) with documentation of preoperative infection, 2 (<0.01%) with all antimicrobial dates and times missing, 1461 (3.7%) with preadmission antimicrobial administration, 1432 (3.7%) with antimicrobial administration for more than 24 hours preoperatively, and 36 cases (0.09%) for other reasons. After exclusions, 34 133 (87.3%) cases from 2965 hospitals (median, 5 cases per hospital; range, 1-386 cases) remained available for analysis.

Patient demographic characteristics are summarized in Table 1. The mean age was 73.3 years (SD, 9.4 years); 89.3% were white; and 58.6% were female. Hip or knee arthroplasty made up the largest group (44%) of operations evaluated. The median length of stay for all patients was 5 days (interquartile range, 4-8 days), and the in-hospital mortality rate was 2.7% (95% CI, 2.5%-2.9%).

Table Graphic Jump LocationTable 1. Demographic Characteristics of Medicare Patients Undergoing Evaluation in the National Surgical Infection Prevention Project*

Only 232 patients (0.7%) did not receive a prophylactic antimicrobial agent. The proportion of patients who received an antimicrobial dose within 60 minutes (120 minutes for vancomycin) before the incision is summarized in Table 2. An explicit incision time was documented for only 11 220 patients (32.9%). Of these, 55.7% (95% CI, 54.8%-56.6%) received an antimicrobial dose in the recommended time frame. We randomly selected and reabstracted 1728 cases for which an explicit incision time was missing. Using proxy times (eg, surgery start time) to approximate the incision time, we estimated that 54.3% of these patients received their antimicrobial dose within 1 hour before incision. Patients undergoing cardiac and orthopedic surgery were more likely to receive an antimicrobial dose within 1 hour before incision. This may reflect the much more common use of preprinted care plans or order forms (50.0% of patients undergoing hip or knee arthroplasty and 36.6% of patients undergoing cardiac surgery), which often included antimicrobial protocols. Preprinted care plans or order forms were found in only 4.0% of colorectal surgery cases, 4.5% of hysterectomy cases, and 5.3% of vascular surgery cases. The distribution of antimicrobial start times related to incision is demonstrated in Figure 1. We noted that 9.6% of patients received their first antimicrobial dose more than 4 hours after incision. For those patients whose operation was still under way more than 4 hours after incision, 12.2% received an additional intraoperative antimicrobial dose.

Place holder to copy figure label and caption
Figure 1.

Documented time of prophylactic antimicrobial administration as related to the surgical incision, based on 11 220 patients who had an explicitly documented incision time. Patients who were being treated for infections before surgery, patients who were receiving antimicrobials before admission, and patients who were receiving antimicrobials for more than 24 hours before surgery were excluded from the study. In addition, patients for whom there were insufficient data to determine timing of antibiotic administration as related to the time of incision and patients undergoing colon surgery who received oral antimicrobial prophylaxis only were excluded from the performance measure (described in Table 2).

Graphic Jump Location
Table Graphic Jump LocationTable 2. Proportion of Patients Who Received a Prophylactic Antimicrobial Within 1 Hour Before the Surgical Incision*

The proportion of patients who received an antimicrobial drug consistent with published guidelines is summarized in Table 3. Most patients (92.6%; 95% CI, 92.3%-92.8%) received a guideline-recommended antimicrobial regimen. The most commonly prescribed agents for patients who received any antimicrobial or combination of antimicrobials consistent with surgical antimicrobial prophylaxis guidelines are summarized in Table 4. First- or second-generation cephalosporins were the most commonly used agents in those cases that met the criteria. In cases of cardiac and vascular surgery and total joint arthroplasty, the antimicrobial most commonly considered inappropriate was vancomycin because of no documentation of a β-lactam allergy. Combinations of ampicillin sodium and sulbactam sodium and of piperacillin sodium and tazobactam sodium, antimicrobials not included in any guidelines for surgical prophylaxis, were the most commonly used drugs in colon surgery cases that failed the performance measure. The proportion of patients who received prophylaxis that was limited to a guideline-recommended regimen (ie, no additional antimicrobials were given beyond those recommended) was 78.7%.

Table Graphic Jump LocationTable 3. Proportion of Patients Who Received a Prophylactic Antimicrobial Drug Consistent With Published Guidelines*
Table Graphic Jump LocationTable 4. Most Commonly Prescribed Agents for Patients Who Received Any Antimicrobial or Combination of Antimicrobials Consistent With Surgical Antimicrobial Prophylaxis Guidelines*

The proportion of cases in which prophylaxis was discontinued within 24 hours after the end of surgery is shown in Table 5 and Figure 2. Only 40.7% (95% CI, 40.2%-41.2%) of patients had their antimicrobial prophylaxis discontinued within 24 hours. Patients undergoing cardiac surgery (34.4%; 95% CI, 33.4%-35.5%) and hip or knee arthroplasty (36.7%; 95% CI, 35.9-37.4) were least likely to have antimicrobial prophylaxis discontinued, although the median duration of antimicrobial prophylaxis was longest (57.0 hours) for patients undergoing colon surgery. At 48 hours after the end of surgery, 26.7% of patients were still receiving prophylaxis, and 9.3% continued to receive prophylaxis for more than 96 hours (Figure 2).

Place holder to copy figure label and caption
Figure 2.

Time of discontinuation of antimicrobial prophylaxis, based on 32 603 patients who received antimicrobial prophylaxis. The bars show the proportion of patients who had their antimicrobial prophylaxis discontinued during each time interval, and the line shows the cumulative proportion of patients whose antimicrobial therapy was discontinued. Cases were excluded from the denominator of this performance measure if there was any documentation in the medical record of an infection during surgery or within 48 hours after the end of surgery. Patients who did not receive prophylactic antimicrobials and patients who underwent more than 1 surgical procedure of interest during the hospitalization were excluded from the performance measure. In addition, patients for whom there were insufficient data to determine the time of antimicrobial discontinuation in relation to the end of surgery were excluded (described in Table 5).

Graphic Jump Location
Table Graphic Jump LocationTable 5. Proportion of Patients Whose Antimicrobial Prophylaxis Was Discontinued Within 24 Hours of the End of Surgery*

Postoperative infections were documented during hospitalization in 2875 patients (8.4%). Pneumonia or other lung infection was documented in 1235 patients (3.6%); urinary tract infections, in 974 (2.9%); bloodstream infections, in 541 (1.6%); and SSIs in 357 (1.0%). Rates of SSIs by procedure type were 1.3% for cardiac surgery, 2.9% for colon surgery, 0.2% for hip or knee arthroplasty, 0.4% for hysterectomy, and 1.7% for vascular surgery. The most commonly documented noninfectious complications included hemorrhage in 1411 patients (4.1%), heart failure or pulmonary edema in 1400 (4.1%), respiratory failure in 1282 (3.8%), and cardiac arrest in 556 (1.6%).

Antimicrobial prophylaxis to prevent SSI is one of the most widely accepted practices in surgery. Optimal prophylaxis requires application in appropriate types of operations, selection of safe and effective antimicrobials, initial administration and redosing to maintain effective serum and tissue levels throughout the operation, and discontinuation when the patient is no longer receiving a benefit.5,17,23,25 The results of this population-based study of selected operations performed on Medicare beneficiaries suggest that essentially all patients (99.3%) receive antimicrobial prophylaxis, but that there is still considerable room for improvement in its timing and discontinuation.

Overall, 55.7% of patients received prophylactic antimicrobials during the 60 minutes (120 minutes for vancomycin) before incision. Prior studies have demonstrated that timing is critical to the effectiveness of prophylaxis, and current guidelines recommend dosing within 1 hour before incision. In 1957, Miles et al15 demonstrated that measures that influenced the development of experimental infections were effective only during the 3 to 4 hours after bacterial contamination of a wound. In 1961, Burke16 reported that a variety of antimicrobials could prevent the development of experimental infections, but only if given within about 3 hours after wound contamination. In randomized clinical trials reported in 1964 and 1969, antimicrobials given before, during, and shortly after abdominal surgery were effective in preventing SSI.17,44 Stone et al18 showed that the lowest rates of SSI in abdominal operations were associated with prophylaxis started within 1 hour before the incision, whereas Classen et al21 reported similar findings for cardiac operations in 1992. It is of interest that 9.6% of the patients in our assessment received their first antimicrobial dose more than 4 hours after incision when little if any benefit would be expected based on these previously published studies.16,18,21

Most (92.6%) of the patients in this assessment received a prophylactic antimicrobial regimen consistent with current guidelines. However, only 78.7% received regimens that were limited to recommended agents, suggesting that a substantial amount of antimicrobials are used unnecessarily.

Many different antimicrobial regimens are effective for preventing SSI. The optimal agent is effective against the organisms that are most likely to be encountered during the type of operation that is to be performed; is safe, inexpensive, and bactericidal; and has a long half-life.25 Several professional organizations have published guidelines for the selection and use of prophylactic antimicrobials.2228 These guidelines generally favor the use of older, relatively narrow-spectrum agents such as the first- and second-generation cephalosporins. There is no evidence that newer antimicrobials are more effective than older options. The prophylactic use of newer, broad-spectrum drugs that are frontline therapeutic agents is generally discouraged because of concern that widespread use will promote the emergence and spread of bacterial strains that are resistant to them. Our data suggest that newer antimicrobials are frequently used when older agents would be effective.

The results of this study raise additional concerns regarding antimicrobial resistance. Our data suggest that vancomycin continues to be used excessively for surgical prophylaxis. The primary indication for use of prophylactic vancomycin is a β-lactam allergy. In almost 50% of the cases in this study where vancomycin was used, there was no documented β-lactam allergy. In addition, 59.3% of patients received prophylaxis for more than 24 hours after the end of surgery. The optimal duration of prophylaxis has been controversial, especially for cardiovascular and orthopedic surgery, where many surgeons prefer to continue prophylaxis until all drains and tubes have been removed. However, the bulk of published evidence, including studies of orthopedic and cardiac surgery, suggests that short-duration prophylaxis—as little as 1 dose in many studies—is equally effective as longer-duration administration in preventing infection.5,2228,4562 There is also evidence that prolonged antimicrobial administration can be harmful to patients by promoting antimicrobial-resistant bacteria and increasing the incidence of antibiotic-associated complications.6371

Our study has several limitations. We only included Medicare patients undergoing 5 major surgical procedures, and our findings may not apply to younger patients or those undergoing other operations. Our findings were limited to information documented in the medical record, and important case findings may have been omitted. This was especially apparent in the lack of an explicitly documented incision time in almost two thirds of the charts. We also had no information on rates of methicillin-resistant Staphylococcus aureus infection in individual hospitals and no information on prior methicillin-resistant S aureus colonization of patients undergoing surgery. This prevented us from determining if there might be legitimate reasons for use of vancomycin in some patients without a documented β-lactam allergy. Vancomycin might be the agent of choice for certain operations when a hospital has high rates of infection with methicillin-resistant S aureus or methicillin-resistant coagulase-negative staphylococci or when a patient has known colonization with these organisms. Unfortunately, an institutional threshold rate that should trigger the use of vancomycin has not been established.25 Routine use of vancomycin for prophylaxis is not justified for any operation type because of the risk of promoting vancomycin-resistant bacteria in the patient and hospital environment. Finally, data on postoperative infections were limited to those documented in the chart. No information about nosocomial infection surveillance or postdischarge complications was available for this study, thereby limiting our ability to compare SSI incidence with existing national data (eg, the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention).38

The findings of this study continue to document the challenges of disseminating evidence-based knowledge systematically and expeditiously into clinical practice.72,73 The scientific basis for antimicrobial prophylaxis was first published more than 40 years ago.1517 When considering the broad range of evidence-based recommendations for clinical practice, appropriate surgical antimicrobial prophylaxis would appear to be a relatively straightforward practice to implement. However, many patients continue to undergo operations without having received antimicrobials during the critical period before incision, and prolonged duration of antimicrobial prophylaxis remains common. Although the demand for high quality and accountability in health care is increasing, greater effort is needed to ensure that proven treatments are routinely implemented in practice. In the recent Institute of Medicine report, Priority Areas for National Action: Transforming Health Care Quality,74 prevention and surveillance of nosocomial infections was recommended as a priority area for health care quality improvement. The authors noted that “prevention of nosocomial infections through the implementation of evidence-based guidelines and a surveillance program demonstrates how effective systems interventions can lead to more widespread improvements in quality of care.” One option to improve surgical antimicrobial prophylaxis and prescribing may be broader development and use of computer-assisted order entry and decision support.75,76

The findings from this baseline evaluation represent the first step in a number of interventions designed to improve the delivery of surgical care in the United States. Medicare quality improvement organizations across the country have implemented local quality improvement initiatives with hospitals to improve delivery of antimicrobial prophylaxis for surgical patients.42 In addition, the Joint Commission on Accreditation of Healthcare Organizations has adopted the 3 National Surgical Infection Prevention Project performance measures as an ORYX core measure initiative (Joint Commission on Accreditation of Healthcare Organizations, Oakbrook Terrace, Ill) that will be used in the future to focus on-site survey evaluation activities.77 The performance measures related to timing, selection, and duration of antimicrobial prophylaxis have been slated for voluntary submission and public reporting of hospital performance beginning in the summer of 2005.78

Substantial opportunities remain to improve the use of prophylactic antimicrobials for patients undergoing major surgery. Achieving high rates of performance for appropriate antimicrobial prophylaxis to prevent SSIs will require the development of systems in which the knowledge from years of research and recommendations from clinical practice guidelines are routinely incorporated into practice.

Correspondence: Dale W. Bratzler, DO, MPH, Oklahoma Foundation for Medical Quality, Inc, 14000 Quail Springs Pkwy, Suite 400, Oklahoma City, OK 73134-2627 (dbratzler@okqio.sdps.org).

Accepted for Publication: July 27, 2004.

Disclaimer: The analyses on which this publication is based were performed under contract 500-99-P619, entitled “Utilization and Quality Control Peer Review Organization for the State of Oklahoma,” sponsored by the Centers for Medicare & Medicaid Services, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and the mention of trade names, commercial products, or organizations does not imply endorsement by the US government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by CMS, which has encouraged identification of quality improvement projects derived from analyses of patterns of care, and therefore required no special funding on the part of this contractor. Ideas and contributions to the authors concerning experience in engaging with issues presented are welcomed.

Acknowledgment: We thank the following professionals who have served on the expert panel for the National Surgical Infection Prevention Project: Jason H. Calhoun, MD, and Arlen D. Hanssen, MD (American Academy of Orthopaedic Surgery, Rosemont, Ill); Justine Medina, RN, MS (American Association of Critical Care Nurses, Aliso Viejo, Calif); Sandra Tunajek, CRNA, MSN (American Association of Nurse Anesthetists, Park Ridge, Ill); Vanessa Dalton, MD, MPH (American College of Obstetricians and Gynecologists, Washington, DC); Philip S. Barie, MD, and Christopher Daly, MD (American College of Surgeons, Chicago, Ill); Robert A. Bonomo, MD (American Geriatrics Society, New York, NY); Carl W. Armstrong, MD (American Hospital Association, Chicago); James E. Cottrell, MD, Lee A Fleisher, MD, and Jonathon R. Gavrin, MD (American Society of Anesthesiologists, Park Ridge); Neil H. Hyman, MD (American Society of Colon and Rectal Surgeons, Arlington Heights, Ill); Keith M. Olsen, PharmD (American Society of Health-System Pharmacists, Bethesda, Md); Leslie Shultz, PhD, CPHQ (Ascension Health, St Louis, Mo); Carol Peterson, RN, BSN, MAOM, CNOR (Association of periOperative Registered Nurses, Denver, Colo); Audrey Adams, RN, MPH, CIC (Association for Professionals in Infection Control and Epidemiology, Washington); Julie Gerberding, MD, MPH, Chesley Richards, MD, MPH, and Lynn Steele, MS, CIC (Centers for Disease Control and Prevention, Atlanta, Ga); Peter M. Houck, MD, and Judy Goldfarb, RN, MA (CMS, Seattle, Wash); James T. Lee, MD, PhD (Healthcare Infection Control Practices Advisory Committee, Atlanta); E. Patchen Dellinger, MD, and Peter Gross, MD (Infectious Diseases Society of America, Alexandria, Va); Sharon Sprenger, RHIA, CPHQ, MPA (Joint Commission on Accreditation of Healthcare Organizations, Oakbrook Terrace, Ill); Gianna Zuccotti, MD, MPH (The Medical Letter, New Rochelle, NY); Dale W. Bratzler, DO, MPH, Karina Carr, RN, and Lisa Red, MSHA (Oklahoma Foundation for Medical Quality, Inc, Oklahoma City); Meera Kelly, MD, George Parkins, MD, Gina Pugliese, RN, MS, Judene Bartley, RN, MPH, and Colleen M. Vetere, RN, MPH (Premier, Inc, Oak Brook, Ill); Rosa Johnson, ARNP, MN (Qualis Health, Seattle); William R. Jarvis, MD, and Edward S. Wong (Society for Healthcare Epidemiology of America, Alexandria); Fred H. Edwards, MD, and Mary Eiken (Society of Thoracic Surgeons, Chicago); Donald E. Fry, MD (Surgical Infection Society, Cincinnati, Ohio); and John A. Hitt, MD (VHA, Inc, Denver).

Financial Disclosure: Dr Fry is a member of the speakers’ bureaus of and has received research grants from Pfizer and Merck. Dr Dellinger has received grants for clinical research from, served on an advisory board for, and/or lectured for honoraria from SmithKline Beecham, Glaxo, Bayer, Eli Lilly, Merck, Wyeth-Ayerst, Pharmacia, Bristol-Myers Squibb, AstraZeneca, Pfizer, Aventis, Hoffmann–La Roche, Arrow, NABI, Ortho-McNeil, Parke-Davis, Abbott, ICOS, Immunex, Chiron, Searle, Cubist, Versicor, InterMune, Peninsula, BRAHMS, and Centocor.

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Polk  HC  JrTrachtenberg  LFinn  MP Antibiotic activity in surgical incisions: the basis for prophylaxis in selected operations. JAMA 1980;2441353- 1354
PubMed
DiPiro  JTVallner  JJBowden  TAClark  BASisley  JF Intraoperative serum and tissue activity of cefazolin and cefoxitin. Arch Surg 1985;120829- 832
PubMed
Classen  DCEvans  RSPestotnik  SLHorn  SDMenlove  RLBurke  JP The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992;326281- 286
PubMed
Page  CPBohnen  JMFletcher  JRMcManus  ATSolumkin  JSWittman  DH Antimicrobial prophylaxis for surgical wounds: guidelines for clinical care. Arch Surg 1993;12879- 88
PubMed
Dellinger  EPGross  PABarrett  TL  et al.  Quality standard for antimicrobial prophylaxis in surgical procedures: Infectious Diseases Society of America. Clin Infect Dis 1994;18422- 427
PubMed
American Society of Health-System Pharmacists, ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 1999;561839- 1888
PubMed
Mangram  AJHoran  TCPearson  ML  et al.  Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1999;20250- 278
PubMed
 Antimicrobial prophylaxis in surgery. Med Lett Drugs Ther 2001;4392- 97[published correction appears in Med Lett Drugs Ther. 2001;43:108].
PubMed
ACOG Committee on Practice Bulletins, Antibiotic Prophylaxis for Gynecologic Procedures.  Washington, DC American College of Obstetricians and Gynecologists January2001;ACOG Practice Bulletin 23
Gilbert  DNMoellering  RCSande  MA The Sanford Guide to Antimicrobial Therapy, 2003. 33rd ed. Hyde Park, Vt Antimicrobial Therapy Inc2003;123- 124
Polk  HC  JrWilson  MA Systemic antibiotic prophylaxis in surgery. Fry  DESurgical Infections Boston, Mass Little Brown & Co Inc1995;127- 133
Silver  AEichorn  AKral  J  et al.  Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. Am J Surg 1996;171548- 552
PubMed
Matuschka  PRCheadle  WGBurke  JDGarrison  RN A new standard of care: administration of preoperative antibiotics in the operating room. Am Surg 1997;63500- 503
PubMed
Gorecki  PSchein  MRucinski  JCWise  L Antibiotic administration in patients undergoing common surgical procedures in a community teaching hospital: the chaos continues. World J Surg 1999;23429- 433
PubMed
Trick  WEScheckler  WETokars  JI  et al.  Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2000;119108- 114
PubMed
Burke  JP Maximizing appropriate antibiotic prophylaxis for surgical patients: anupdate from LDS Hospital, Salt Lake City. Clin Infect Dis 2001;33 ((suppl 2)) S78- S83
PubMed
Richards  CEmori  TGPeavy  GGaynes  RP Promoting quality through measurement of performance and response: prevention success stories. Emerg Infect Dis 2001;7299- 301
PubMed
Gaynes  RRichards  CEdwards  J  et al.  Feeding back surveillance data to prevent hospital-acquired infections. Emerg Infect Dis 2001;7295- 298
PubMed
Gaynes  RPCulver  DHHoran  TC  et al.  Surgical site infection (SSI) rates in the United States, 1992-1998: the National Nosocomial Infections Surveillance System basic SSI risk index. Clin Infect Dis 2001;33 ((suppl 2)) S69- S77
PubMed
National Nosocomial Infections Surveillance System, National Nosocomial Infections Surveillance (NNIS) System Report: data summary from January 1992 to June 2002, issued August 2002. Am J Infect Control 2002;30458- 475
PubMed
Jencks  SFWilensky  GR The Health Care Quality Improvement Initiative: a new approach to quality assurance in Medicare. JAMA 1992;268900- 904
PubMed
Jencks  SFCuerdon  TBurwen  DR  et al.  Quality of medical care delivered to Medicare beneficiaries: a profile at state and national levels. JAMA 2000;2841670- 1676
PubMed
Jencks  SFHuff  EDCuerdon  T Change in the quality of care delivered to Medicare beneficiaries 1998-1999 to 2000-2001. JAMA 2003;289305- 312
PubMed
 Surgical Infection Prevention Project description. Available at: http://www.medqic.org/sip. Accessed April 20, 2004
US Public Health Service, International Classification of Diseases, Ninth Revision: Clinical Modification. 4th ed. Washington, DC US Dept of Health and Human Services1991;Report PHS91-1260
Bernard  HRCole  WR The prophylaxis of surgical infection: the effect of prophylactic antimicrobial drugs on the incidence of infection following potentially contaminated operations. Surgery 1964;56151- 157
PubMed
Meijer  WSSchmitz  PIJeekel  J Meta-analysis of randomized, controlled clinical trials of antibiotic prophylaxis in biliary tract surgery. Br J Surg 1990;77283- 290
PubMed
Kreter  BWoods  M Antibiotic prophylaxis for cardiothoracic operations: meta-analysis of thirty years of clinical trials. J Thorac Cardiovasc Surg 1992;104590- 599
PubMed
McDonald  MGrabsch  EMarshall  CForbes  A Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review. Aust N Z J Surg 1998;68388- 396
PubMed
Pollard  JPHughes  SOScott  JEEvans  MJBenson  MK Antibiotic prophylaxis in total hip replacement. BMJ 1979;1707- 709
PubMed
Williams  DNGustilo  RBBeverly  RKind  AC Bone and serum concentrations of five cephalosporin drugs: relevance to prophylaxis and treatment in orthopedic surgery. Clin Orthop 1983;179253- 265
PubMed
Nelson  CLGreen  TGPorter  RAWarren  RD One day versus seven days of preventive antibiotic therapy in orthopedic surgery. Clin Orthop 1983;176258- 263
PubMed
Heydemann  JSNelson  CL Short-term preventive antibiotics. Clin Orthop 1986;205184- 187
PubMed
Oishi  CSCarrion  WVHoaglund  FT Use of parenteral prophylactic antibiotics in clean orthopaedic surgery: a review of the literature. Clin Orthop 1993;296249- 255
PubMed
Mauerhan  DRNelson  CLSmith  DL  et al.  Prophylaxis against infection in total joint arthroplasty: one day of cefuroxime compared with three days of cefazolin. J Bone Joint Surg Am 1994;7639- 45
PubMed
Conte  JE  JrCohen  SNRoe  BBElashoff  RM Antibiotic prophylaxis and cardiac surgery: a prospective double-blind comparison of single-dose versus multiple-dose regimens. Ann Intern Med 1972;76943- 949
PubMed
Goldmann  DAHopkins  CCKarchmer  AW  et al.  Cephalothin prophylaxis in cardiac valve surgery: a prospective, double-blind comparison of two-day and six-day regimens. J Thorac Cardiovasc Surg 1977;73470- 479
PubMed
Hillis  DJRosenfelt  FLSpicer  WJStirling  GR Antibiotic prophylaxis for coronary bypass grafting: comparison of a five-day and a two-day course. J Thorac Cardiovasc Surg 1983;86217- 221
PubMed
Geroulanos  SDonfried  BSchumacher  FTurina  M Cefuroxime versus ceftriaxone prophylaxis in cardiovascular surgery. Drugs Exp Clin Res 1985;11201- 205
PubMed
Nooyen  SMOverbeek  BPBrutel de la Riviere  AStorm  AJLangemeyer  JJ Prospective randomized comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting. Eur J Clin Microbiol Infect Dis 1994;131033- 1037
PubMed
Vuorisalo  SPokela  RSyrjala  J Is single-dose prophylaxis sufficient for coronary artery bypass surgery? an analysis of peri- and postoperative serum cefuroxime and vancomycin levels. J Hosp Infect 1997;37237- 247
PubMed
Kriaras  IMichalopoulos  AMichalis  A  et al.  Antibiotic prophylaxis in cardiac surgery. J Cardiovasc Surg (Torino) 1997;38605- 610
PubMed
Salminen  USViljanen  TUValtonen  VVIkonen  TESahlman  AEHarjula  AL Ceftriaxone versus vancomycin prophylaxis in cardiovascular surgery. J Antimicrob Chemother 1999;44287- 290
PubMed
Bucknell  SJMohajeri  MLow  JMcDonald  MHill  DG Single- versus multiple-dose antibiotics prophylaxis for cardiac surgery. Aust N Z J Surg 2000;70409- 411
PubMed
Archer  GLArmstrong  BC Alteration of staphylococcal flora in cardiac surgery patients receiving antibiotic prophylaxis. J Infect Dis 1983;147642- 649
PubMed
Kernodle  DSBarg  NLKaiser  AB Low-level colonization of hospitalized patients with methicillin-resistant coagulase-negative staphylococci and emergence of the organisms during surgical antimicrobial prophylaxis. Antimicrob Agents Chemother 1988;32202- 208
PubMed
Archer  GL Alteration of cutaneous staphylococcal flora as a consequence of antimicrobial prophylaxis. Rev Infect Dis 1991;13 ((suppl 10)) S805- S809
PubMed
Terpstra  SNoodhoek  GTVoesten  HGHendriks  BDegene  JE Rapid emergence of resistant coagulase-negative staphylococci on the skin after antimicrobial prophylaxis. J Hosp Infect 1999;43195- 202
PubMed
Harbarth  SSamore  MHLichtenberg  DCarmeli  Y Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance. Circulation 2000;1012916- 2921
PubMed
Eggimann  PPittet  D Infection control in the ICU. Chest 2001;1202059- 2093
PubMed
Takesue  YYokoyama  TAkagi  S  et al.  Changes in the intestinal flora after the administration of prophylactic antibiotics to patients undergoing a gastrectomy. Surg Today 2002;32581- 586
PubMed
Hecker  MTAron  DCPatel  NPLehmann  MKDonskey  CJ Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity. Arch Intern Med 2003;163972- 978
PubMed
Hoth  JJFranklin  GAStassen  NAGirard  SMRodriguez  RJRodriguez  JL Prophylactic antibiotics adversely affect nosocomial pneumonia in trauma patients. J Trauma 2003;55249- 254
PubMed
Institute of Medicine, Crossing the Quality Chasm: A New Health System for the 21st Century.  Washington, DC National Academy Press2001;
Berwick  DM Disseminating innovations in health care. JAMA 2003;2891969- 1975
PubMed
Institute of Medicine, Priority Areas for National Action: Transforming Health Care Quality. Adams  KCorrigan  JM Washington, DC National Academy Press2003;
Pestotnik  SLClassen  DCEvans  RSBurke  JP Implementing antibiotic practice guidelines through computer-assisted decision support: clinical and financial outcomes. Ann Intern Med 1996;124884- 890
PubMed
Evans  RSPestotnik  SLClassen  DC  et al.  A computer-assisted management program for antibiotics and other antiinfective agents. N Engl J Med 1998;338232- 238
PubMed
Joint Commission on Accreditation of Healthcare Organizations, Surgical infection prevention core performance measures for national implementation. Available at: http://www.jcaho.org/pms/core+measures/10asipmeaslistpop.pdf. Accessed April 20, 2004
American Hospital Association, The Quality Initiative: Full Medicare Inpatient Update Requirements and New Measures. Available at: http://www.hospitalconnect.com/aha/key_issues/patient_safety/advocacy/040408qualityadvisory.html. Accessed April 20, 2004

Figures

Place holder to copy figure label and caption
Figure 1.

Documented time of prophylactic antimicrobial administration as related to the surgical incision, based on 11 220 patients who had an explicitly documented incision time. Patients who were being treated for infections before surgery, patients who were receiving antimicrobials before admission, and patients who were receiving antimicrobials for more than 24 hours before surgery were excluded from the study. In addition, patients for whom there were insufficient data to determine timing of antibiotic administration as related to the time of incision and patients undergoing colon surgery who received oral antimicrobial prophylaxis only were excluded from the performance measure (described in Table 2).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Time of discontinuation of antimicrobial prophylaxis, based on 32 603 patients who received antimicrobial prophylaxis. The bars show the proportion of patients who had their antimicrobial prophylaxis discontinued during each time interval, and the line shows the cumulative proportion of patients whose antimicrobial therapy was discontinued. Cases were excluded from the denominator of this performance measure if there was any documentation in the medical record of an infection during surgery or within 48 hours after the end of surgery. Patients who did not receive prophylactic antimicrobials and patients who underwent more than 1 surgical procedure of interest during the hospitalization were excluded from the performance measure. In addition, patients for whom there were insufficient data to determine the time of antimicrobial discontinuation in relation to the end of surgery were excluded (described in Table 5).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic Characteristics of Medicare Patients Undergoing Evaluation in the National Surgical Infection Prevention Project*
Table Graphic Jump LocationTable 2. Proportion of Patients Who Received a Prophylactic Antimicrobial Within 1 Hour Before the Surgical Incision*
Table Graphic Jump LocationTable 3. Proportion of Patients Who Received a Prophylactic Antimicrobial Drug Consistent With Published Guidelines*
Table Graphic Jump LocationTable 4. Most Commonly Prescribed Agents for Patients Who Received Any Antimicrobial or Combination of Antimicrobials Consistent With Surgical Antimicrobial Prophylaxis Guidelines*
Table Graphic Jump LocationTable 5. Proportion of Patients Whose Antimicrobial Prophylaxis Was Discontinued Within 24 Hours of the End of Surgery*

References

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Martone  WJJarvis  WRCulver  DHHaley  RW Incidence and nature of endemic and epidemic nosocomial infections. Bennett  JVBrachman  PSHospital Infections 3rd ed. Boston, Mass Little Brown & Co Inc1992;577- 596
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Jenney  AWHarrington  GARusso  PLSpelman  DW Cost of surgical site infections following coronary artery bypass surgery. Aust N Z J Surg 2001;71662- 664
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Fry  DE The economic costs of surgical site infection. Surg Infect (Larchmt) 2002;3 ((suppl 1)) S37- S43
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Hollenbeak  CSMurphy  DDunagan  WCFraser  VJ Nonrandom selection and the attributable cost of surgical-site infections. Infect Control Hosp Epidemiol 2002;23177- 182
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Burke  JF The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1961;50161- 168
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Stone  HHHooper  CAKolb  LDGeheber  CEDawkins  EJ Antibiotic prophylaxis in gastric, biliary and colonic surgery. Ann Surg 1976;184443- 452
PubMed
Polk  HC  JrTrachtenberg  LFinn  MP Antibiotic activity in surgical incisions: the basis for prophylaxis in selected operations. JAMA 1980;2441353- 1354
PubMed
DiPiro  JTVallner  JJBowden  TAClark  BASisley  JF Intraoperative serum and tissue activity of cefazolin and cefoxitin. Arch Surg 1985;120829- 832
PubMed
Classen  DCEvans  RSPestotnik  SLHorn  SDMenlove  RLBurke  JP The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992;326281- 286
PubMed
Page  CPBohnen  JMFletcher  JRMcManus  ATSolumkin  JSWittman  DH Antimicrobial prophylaxis for surgical wounds: guidelines for clinical care. Arch Surg 1993;12879- 88
PubMed
Dellinger  EPGross  PABarrett  TL  et al.  Quality standard for antimicrobial prophylaxis in surgical procedures: Infectious Diseases Society of America. Clin Infect Dis 1994;18422- 427
PubMed
American Society of Health-System Pharmacists, ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 1999;561839- 1888
PubMed
Mangram  AJHoran  TCPearson  ML  et al.  Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1999;20250- 278
PubMed
 Antimicrobial prophylaxis in surgery. Med Lett Drugs Ther 2001;4392- 97[published correction appears in Med Lett Drugs Ther. 2001;43:108].
PubMed
ACOG Committee on Practice Bulletins, Antibiotic Prophylaxis for Gynecologic Procedures.  Washington, DC American College of Obstetricians and Gynecologists January2001;ACOG Practice Bulletin 23
Gilbert  DNMoellering  RCSande  MA The Sanford Guide to Antimicrobial Therapy, 2003. 33rd ed. Hyde Park, Vt Antimicrobial Therapy Inc2003;123- 124
Polk  HC  JrWilson  MA Systemic antibiotic prophylaxis in surgery. Fry  DESurgical Infections Boston, Mass Little Brown & Co Inc1995;127- 133
Silver  AEichorn  AKral  J  et al.  Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. Am J Surg 1996;171548- 552
PubMed
Matuschka  PRCheadle  WGBurke  JDGarrison  RN A new standard of care: administration of preoperative antibiotics in the operating room. Am Surg 1997;63500- 503
PubMed
Gorecki  PSchein  MRucinski  JCWise  L Antibiotic administration in patients undergoing common surgical procedures in a community teaching hospital: the chaos continues. World J Surg 1999;23429- 433
PubMed
Trick  WEScheckler  WETokars  JI  et al.  Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2000;119108- 114
PubMed
Burke  JP Maximizing appropriate antibiotic prophylaxis for surgical patients: anupdate from LDS Hospital, Salt Lake City. Clin Infect Dis 2001;33 ((suppl 2)) S78- S83
PubMed
Richards  CEmori  TGPeavy  GGaynes  RP Promoting quality through measurement of performance and response: prevention success stories. Emerg Infect Dis 2001;7299- 301
PubMed
Gaynes  RRichards  CEdwards  J  et al.  Feeding back surveillance data to prevent hospital-acquired infections. Emerg Infect Dis 2001;7295- 298
PubMed
Gaynes  RPCulver  DHHoran  TC  et al.  Surgical site infection (SSI) rates in the United States, 1992-1998: the National Nosocomial Infections Surveillance System basic SSI risk index. Clin Infect Dis 2001;33 ((suppl 2)) S69- S77
PubMed
National Nosocomial Infections Surveillance System, National Nosocomial Infections Surveillance (NNIS) System Report: data summary from January 1992 to June 2002, issued August 2002. Am J Infect Control 2002;30458- 475
PubMed
Jencks  SFWilensky  GR The Health Care Quality Improvement Initiative: a new approach to quality assurance in Medicare. JAMA 1992;268900- 904
PubMed
Jencks  SFCuerdon  TBurwen  DR  et al.  Quality of medical care delivered to Medicare beneficiaries: a profile at state and national levels. JAMA 2000;2841670- 1676
PubMed
Jencks  SFHuff  EDCuerdon  T Change in the quality of care delivered to Medicare beneficiaries 1998-1999 to 2000-2001. JAMA 2003;289305- 312
PubMed
 Surgical Infection Prevention Project description. Available at: http://www.medqic.org/sip. Accessed April 20, 2004
US Public Health Service, International Classification of Diseases, Ninth Revision: Clinical Modification. 4th ed. Washington, DC US Dept of Health and Human Services1991;Report PHS91-1260
Bernard  HRCole  WR The prophylaxis of surgical infection: the effect of prophylactic antimicrobial drugs on the incidence of infection following potentially contaminated operations. Surgery 1964;56151- 157
PubMed
Meijer  WSSchmitz  PIJeekel  J Meta-analysis of randomized, controlled clinical trials of antibiotic prophylaxis in biliary tract surgery. Br J Surg 1990;77283- 290
PubMed
Kreter  BWoods  M Antibiotic prophylaxis for cardiothoracic operations: meta-analysis of thirty years of clinical trials. J Thorac Cardiovasc Surg 1992;104590- 599
PubMed
McDonald  MGrabsch  EMarshall  CForbes  A Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review. Aust N Z J Surg 1998;68388- 396
PubMed
Pollard  JPHughes  SOScott  JEEvans  MJBenson  MK Antibiotic prophylaxis in total hip replacement. BMJ 1979;1707- 709
PubMed
Williams  DNGustilo  RBBeverly  RKind  AC Bone and serum concentrations of five cephalosporin drugs: relevance to prophylaxis and treatment in orthopedic surgery. Clin Orthop 1983;179253- 265
PubMed
Nelson  CLGreen  TGPorter  RAWarren  RD One day versus seven days of preventive antibiotic therapy in orthopedic surgery. Clin Orthop 1983;176258- 263
PubMed
Heydemann  JSNelson  CL Short-term preventive antibiotics. Clin Orthop 1986;205184- 187
PubMed
Oishi  CSCarrion  WVHoaglund  FT Use of parenteral prophylactic antibiotics in clean orthopaedic surgery: a review of the literature. Clin Orthop 1993;296249- 255
PubMed
Mauerhan  DRNelson  CLSmith  DL  et al.  Prophylaxis against infection in total joint arthroplasty: one day of cefuroxime compared with three days of cefazolin. J Bone Joint Surg Am 1994;7639- 45
PubMed
Conte  JE  JrCohen  SNRoe  BBElashoff  RM Antibiotic prophylaxis and cardiac surgery: a prospective double-blind comparison of single-dose versus multiple-dose regimens. Ann Intern Med 1972;76943- 949
PubMed
Goldmann  DAHopkins  CCKarchmer  AW  et al.  Cephalothin prophylaxis in cardiac valve surgery: a prospective, double-blind comparison of two-day and six-day regimens. J Thorac Cardiovasc Surg 1977;73470- 479
PubMed
Hillis  DJRosenfelt  FLSpicer  WJStirling  GR Antibiotic prophylaxis for coronary bypass grafting: comparison of a five-day and a two-day course. J Thorac Cardiovasc Surg 1983;86217- 221
PubMed
Geroulanos  SDonfried  BSchumacher  FTurina  M Cefuroxime versus ceftriaxone prophylaxis in cardiovascular surgery. Drugs Exp Clin Res 1985;11201- 205
PubMed
Nooyen  SMOverbeek  BPBrutel de la Riviere  AStorm  AJLangemeyer  JJ Prospective randomized comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting. Eur J Clin Microbiol Infect Dis 1994;131033- 1037
PubMed
Vuorisalo  SPokela  RSyrjala  J Is single-dose prophylaxis sufficient for coronary artery bypass surgery? an analysis of peri- and postoperative serum cefuroxime and vancomycin levels. J Hosp Infect 1997;37237- 247
PubMed
Kriaras  IMichalopoulos  AMichalis  A  et al.  Antibiotic prophylaxis in cardiac surgery. J Cardiovasc Surg (Torino) 1997;38605- 610
PubMed
Salminen  USViljanen  TUValtonen  VVIkonen  TESahlman  AEHarjula  AL Ceftriaxone versus vancomycin prophylaxis in cardiovascular surgery. J Antimicrob Chemother 1999;44287- 290
PubMed
Bucknell  SJMohajeri  MLow  JMcDonald  MHill  DG Single- versus multiple-dose antibiotics prophylaxis for cardiac surgery. Aust N Z J Surg 2000;70409- 411
PubMed
Archer  GLArmstrong  BC Alteration of staphylococcal flora in cardiac surgery patients receiving antibiotic prophylaxis. J Infect Dis 1983;147642- 649
PubMed
Kernodle  DSBarg  NLKaiser  AB Low-level colonization of hospitalized patients with methicillin-resistant coagulase-negative staphylococci and emergence of the organisms during surgical antimicrobial prophylaxis. Antimicrob Agents Chemother 1988;32202- 208
PubMed
Archer  GL Alteration of cutaneous staphylococcal flora as a consequence of antimicrobial prophylaxis. Rev Infect Dis 1991;13 ((suppl 10)) S805- S809
PubMed
Terpstra  SNoodhoek  GTVoesten  HGHendriks  BDegene  JE Rapid emergence of resistant coagulase-negative staphylococci on the skin after antimicrobial prophylaxis. J Hosp Infect 1999;43195- 202
PubMed
Harbarth  SSamore  MHLichtenberg  DCarmeli  Y Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance. Circulation 2000;1012916- 2921
PubMed
Eggimann  PPittet  D Infection control in the ICU. Chest 2001;1202059- 2093
PubMed
Takesue  YYokoyama  TAkagi  S  et al.  Changes in the intestinal flora after the administration of prophylactic antibiotics to patients undergoing a gastrectomy. Surg Today 2002;32581- 586
PubMed
Hecker  MTAron  DCPatel  NPLehmann  MKDonskey  CJ Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity. Arch Intern Med 2003;163972- 978
PubMed
Hoth  JJFranklin  GAStassen  NAGirard  SMRodriguez  RJRodriguez  JL Prophylactic antibiotics adversely affect nosocomial pneumonia in trauma patients. J Trauma 2003;55249- 254
PubMed
Institute of Medicine, Crossing the Quality Chasm: A New Health System for the 21st Century.  Washington, DC National Academy Press2001;
Berwick  DM Disseminating innovations in health care. JAMA 2003;2891969- 1975
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