Original Article
Perioperative Antibiotic Prophylaxis for Herniorrhaphy and Breast Surgery
N Engl J Med 1990; 322:153-160January 18, 1990
- Abstract
- Abstract
We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made.
The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not (MantelHaenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01). For patients undergoing a procedure involving the breast, infection occurred in 6.6 percent of the cefonicid recipients (20 of 303) and 12.2 percent of the placebo recipients (37 of 303); for those undergoing herniorrhaphy, infection occurred in 2.3 percent of the cefonicid recipients (7 of 301) and 4.2 percent of the placebo recipients (13 of 311). There were comparable reductions in the numbers of definite wound infections (MantelHaenszel risk ratio, 0.49), wounds that drained pus (risk ratio, 0.43), Staphylococcus aureus wound isolates (risk ratio, 0.49), and urinary tract infections (risk ratio, 0.40). There were also comparable reductions in the need for postoperative antibiotic therapy, non-routine visits to a physician for problems involving wound healing, incision and drainage procedures, and readmission because of problems with wound healing.
We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery. (N Engl J Med 1990; 322:153–60.)
Media in This Article
Figure 1
Percentages of Patients in the Cefonicid and Placebo Groups with Infections of Any Type, Wound Infections, and Urinary Tract Infections after Breast or Hernia Procedures.Figure 2
Percentages of Patients in the Cefonicid and Placebo Groups Who Received Postoperative Antibiotic, Had an Unscheduled Visit to a Physician for a Problem with Wound Healing, or Required Readmission for Infection or Poor Wound Healing after Breast or Hernia Procedures.Article Activity
- Article
PERIOPERATIVE antibiotic prophylaxis reduces the risk of postoperative infection in a number of settings. Our knowledge of this effect comes both from studies in animals1 and from randomized clinical trials.2 The clinical trials supporting the use of prophylaxis include both those involving "clean—contaminated" procedures, such as colorectal surgery,3 in which the operative field becomes contaminated by the host's own flora, and those involving extensive "clean" procedures, such as hip arthroplasty and cardiothoracic surgery.4 , 5 In general, prophylaxis has not been recommended for less extensive clean procedures. However, to our knowledge no randomized clinical trial has examined the value of prophylaxis for relatively simple clean procedures, such as mastectomy or herniorrhaphy, despite the fact that these and similar clean procedures are performed commonly. (For example, approximately 141,000 mastectomies and 329,000 herniorrhaphies were performed in the United States in 1987.6) The absence of such trials is in part a consequence of the perception that the risk of clinically important infection is not large enough to justify the routine use of prophylaxis. However, a number of prospective analyses report a risk of wound infection ranging from 4 to 18 percent after breast surgery7 8 9 10 11 and from 1 to 4 percent after herniorrhaphy.12 13 14 15 Review of these procedures in several of our institutions indicated that infections of all types occurred in 5 to 12 percent of patients (unpublished data). We also found substantial use of prophylaxis by the surgeons in our institutions (in 25 percent of patients undergoing breast surgery and 15 percent of those undergoing herniorrhaphy) despite the absence of studies demonstrating benefit.
We therefore conducted a randomized, double-blind, placebo-controlled evaluation of perioperative antibiotic prophylaxis to determine whether it effects a clinically meaningful reduction in postoperative infections and their sequelae in patients undergoing clean surgical procedures. We evaluated herniorrhaphy and breast surgery because they are performed commonly and the principal mechanism of infection for both is contamination of the operative field by skin flora or environmental organisms.
Methods
Patient Population
The patients were enrolled between April 1, 1985, and September 30, 1987, at the following hospitals: Beth Israel Hospital, Brigham and Women's Hospital, Massachusetts General Hospital, and New England Deaconess Hospital, all in Boston; Harborview Medical Center, University of Washington Hospital, and Pacific Medical Center in Seattle; and Baptist Medical Center and the Veterans Affairs Hospital in Columbia, S.C. Each of the four hospitals in Boston was considered a separate center; the Seattle hospitals were considered to be a single center, as were the Columbia hospitals. The experimental protocol was approved by each institution's research committee, and all patients gave written informed consent to participate.
Patients undergoing elective inguinal herniorrhaphy, femoral herniorrhaphy, mastectomy, lumpectomy, excisional breast biopsy, axillary-node dissection for breast cancer, or reduction mammoplasty were eligible for the study. Patients were not eligible if the surgery was expected to involve the insertion of prosthetic material (e.g., mesh or tissue expanders) or a second incision (e.g., prostatic biopsy). There were several additional requirements for eligibility. The patient had to be at least 18 years old, speak English, live within 35 miles of the hospital at which the surgery was performed, have no recognized infection at the time of surgery, have received no antibiotic therapy during the week before surgery, have no allergy to beta-lactam antibiotics, and not be known to be pregnant or nursing. Some hospitals also excluded patients undergoing outpatient surgery, because of logistical difficulties in obtaining informed consent. All patients had a urine culture performed during the four weeks before surgery.
Treatment Regimens
The study patients received cefonicid (1 g) or an identical-appearing placebo, mixed in 50 ml of 5 percent dextrose in water, as a rapid intravenous infusion no more than 90 minutes before surgery. The placebo was a mixture of glycine, mannitol, and riboflavin.
Randomization and Blinding
At each institution, patients undergoing herniorrhaphy or an eligible procedure involving the breast were randomly assigned separately in blocks of 10 to receive cefonicid or placebo. Block randomization was used to ensure a balanced assignment to the two regimens within institutions and for types of procedure.
Cefonicid and placebo were supplied in identical numbered vials. The treatment codes were not known by anyone at the participating centers, unless the sealed, opaque label attached to each vial was opened. As a consequence, drug assignments were not known during any follow-up evaluations, including nonscheduled visits for suspected wound infection. Investigators were required to return these labels intact or to indicate the reason for opening them. None of the personnel at the data processing or coordinating center knew the treatment codes, and the codes were not revealed to the patients or medical personnel until the last one completed the evaluation.
Definitions of Infection
A definite wound infection was defined as a wound with erythema and drainage, a wound with purulent drainage, or a wound that was opened and not reclosed. A probable wound infection was considered to be present if erythema extended at least 2 cm from the wound in any direction or a physician had diagnosed an infection even though the criteria for definite infection had not been met.
Bacteremia was deemed definite if two blood cultures contained the same organism, one positive blood culture contained a species that had been recovered from a different site, or one positive blood culture was obtained in association with otherwise unexplained fever (temperature, >38°C). Bacteremia was deemed probable if one positive blood culture was obtained in the absence of fever and the patient then began taking an antibiotic that was active against the isolate.
A definite urinary tract infection was defined on the basis of a negative preoperative urine culture plus either two consecutive urine specimens containing at least 100,000 colonies of the same organism per milliliter or one positive urine culture with either fever or local symptoms of urinary tract infection. A probable urinary tract infection was defined on the basis of a negative preoperative urine culture plus one positive postoperative culture and no symptoms or follow-up culture.
Pneumonia was deemed definite if purulent sputum was present as well as otherwise unexplained pulmonary infiltrates and either fever or respiratory symptoms. Pneumonia was considered probable if purulent sputum and otherwise unexplained pulmonary infiltrates were present.
Other infections were classified on an ad hoc basis as either related or unrelated to the surgical procedure. For example, cellulitis at an intravenous-infusion site was considered to be related, since the intravenous catheter was placed because of the procedure, whereas cellulitis at the site of a splinter was not considered to be related to the surgery. Finally, to evaluate the overall efficacy of the prophylactic regimens, a patient with more than one infection was counted only once, although all infections were used for the comparisons of individual types of infections.
Surveillance for Postoperative Infection
A member of the study team, either a nurse or physician, examined each patient's wounds on each weekday during the hospitalization. The wounds were viewed directly when this was possible. When direct inspection was not possible — for instance, when dressings were changed only by the attending physician — notes in the medical record and interviews with personnel were used. A urine specimen was obtained from each patient for culture between three and seven days after surgery. When possible, the patient was examined by a member of the study team between 6 and 15 days after surgery. When this examination was not possible, the physician's office notes were used.
A standardized questionnaire was administered by telephone four to six weeks after surgery. Although follow-up information obtained as late as 12 weeks (84 days) after surgery was accepted, the history obtained during late interviews was restricted to events that occurred during the first 6 weeks. The follow-up questionnaire elicited information about difficulties with wound healing, new infections, new antibiotic courses, nonroutine visits to the physician, and hospitalization. Information suggesting infection was amplified by reference to applicable medical records. A diagnosis of infection obtained at a late interview was accepted only if there was an objective record of the infection dated within 42 days of surgery.
All study-team members (physicians and nurses) reviewed all cases of possible infections together and established final classifications. The cases were reviewed periodically during the course of the study. At the conclusion, all cases of infections were reviewed again to ensure uniform classification. In addition, all cases for which erythema or drainage was reported on the case-report form were reviewed by all investigators. As noted above, all investigators were unaware of the treatment codes until the last evaluation was completed.
Other Data Sources
Information concerning the surgical procedure, including the times of administration of the prophylactic agent and of incision and closure of the skin, the types of antiseptic used, and the amount of blood administered, was obtained from the anesthetists' and other operative records shortly after the procedure and from the dictated operative notes. Other information was obtained concurrently, either by interviewing the patient or the patient's medical staff or by reviewing the medical record.
Determination of Sample Size
The principal hypothesis, specified at the outset, was that prophylaxis would reduce the overall risk of postoperative infection. We also assumed that prophylaxis would prevent the same proportion of infections after herniorrhaphy and after breast surgery, even though the overall risks of infection might differ between the procedures.
A sample of 1000 was chosen to give 75 percent power to find a 40 percent reduction in the overall risk of infection from an anticipated base-line risk of 10 percent among recipients of placebo. This assumption of a reduction in the risk of infection implies the use of a one-tailed test of significance. Such use is consistent with the fact that we saw no important reason to test the unlikely hypothesis that prophylaxis increased the risk of infection. However, since the use of one-tailed tests is controversial, we used two-tailed tests when we analyzed the data.
Inclusions and Exclusions after Randomization
Enough patients were randomly assigned to the treatment group to ensure that 1000 would meet the Food and Drug Administration's criteria for evaluation, as we understood them. However, all patients to whom a study drug was assigned were included in the following analyses, without regard to the FDA criteria, unless no eligible procedure was performed, a concomitant ineligible procedure was performed, a preexisting infection (other than urinary tract infection) was recognized, another antibiotic was administered between randomization and midnight on the day of surgery, no study medication was administered, or no postoperative follow-up could be performed. These exclusion criteria were established before the randomization codes were broken. Patients whose preoperative urine cultures were positive were excluded from the analysis of urinary tract but not other infections.
Statistical Analysis
Stratification was used to control for the possibility of differential effects according to procedure and for confounding by procedure and other potential events. All analyses were controlled for at least two categories of surgery (breast procedure or hernia procedure). For every stratified comparison, a test of homogeneity was performed to determine whether it was reasonable to report a summary result for the stratified comparison. Summary measures are only reported if there was no significant heterogeneity.
MantelHaenszel methods were used to compute summary odds ratios. Exact methods for comparing stratified 2-by-2 tables were used to assess homogeneity and to compute two-tailed P values. Ninety-five percent confidence limits for the common odds ratios were formed with the use of a mid—P value adjustment.16 Comparisons of continuous variables were made with the Wilcoxon rank-sum test.17 We computed odds ratios rather than risk ratios because exact confidence limits can be computed for odds ratios. However, the risks and odds were extremely close in the instances cited here. Therefore, as an aid to readers more familiar with relative risk, the odds ratios are reported as risk ratios and MantelHaenszel odds ratios are reported as MantelHaenszel risk ratios.
Data Processing
Automated data processing and analyses were performed at the Channing Laboratory. Drug assignments were confirmed for infected patients by checking the original printing records for the labels that were attached to the medication vials.
Results
Patient Population
A total of 1319 patients were randomly assigned to receive either cefonicid or placebo from among 4482 who were scheduled for eligible procedures. The reasons for not including the remainder in the randomization were the existence of an exclusion criterion (1035 patients), the patient's refusal to participate (920), an inability to discuss the procedure with the patient (763), and the surgeon's refusal to allow the patient to participate (445). A total of 101 patients were excluded from the analysis after being assigned to the cefonicid or placebo group for the reasons shown in Table 1Table 1
Reasons for the Exclusion of Patients from Analysis after Randomization.. All 101 patients, except the 6 who were lost to follow-up, were excluded because of events that effectively represented late disqualifications that occurred after the assignment to the study drug or placebo group but before substantive entry into the study. There were postoperative infections in four of the excluded patients. Two of these patients had been randomly assigned to each regimen, although none of the four received their assigned antibiotic or placebo. The base-line characteristics of the 1218 patients who were analyzed are shown in Table 2Table 2
Base-Line Characteristics of the Patients Studied.*. Although the number of patients randomly assigned to groups differed substantially between centers, the proportion of such patients with data that could be analyzed was between 91 percent and 95 percent at each center. The numbers of patients included in the analysis and the total number randomly assigned to receive either cefonicid or placebo at the six centers were 101 of 107 (94 percent), 131 of 143 (92 percent), 177 of 193 (92 percent), 213 of 233 (91 percent), 273 of 288 (95 percent), and 323 of 355 (91 percent). There were no important differences between the two treatment groups with regard to the variables shown or others that we evaluated, including hospital, diagnosis of breast cancer, month of the year, or history of alcoholism, steroid therapy, neutropenia, or asplenia.Lumpectomy and modified radical mastectomies accounted for 90 percent of the procedures involving the breast. Inguinal herniorrhaphy accounted for 98 percent of the hernia procedures. Selected characteristics of the procedures are shown in Table 3Table 3
Characteristics of the Surgical Procedures.*. The placebo and cefonicid groups did not differ with regard to the features noted in the table or others we measured, including the number who received their prophylactic doses more than 90 minutes before surgery started or after surgery began; the number who had concomitant axillary-node dissection, skin grafting, or flap reconstruction; the number of drains placed; the type of anesthesia; or the likelihood of intubation.The status of 99 percent (599) of the cefonicid recipients and 99 percent (609) of the placebo recipients was known six or more days after surgery. The intermediate follow-up evaluation, scheduled to occur 5 to 15 days after surgery, was performed in 78 percent (469) of the cefonicid recipients and 75 percent (461) of the placebo recipients. In both groups this evaluation occurred an average of 10 days after surgery. Seventy-two percent of the follow-up evaluations included direct examination. Ninety-eight percent (590) of the cefonicid recipients and 97 percent (594) of the placebo recipients had a final evaluation at least four weeks after surgery. The average interval between surgery and the follow-up evaluation was 38 days in both groups.
Postoperative Infections
Forty-eight percent fewer probable or definite postoperative infections related to the surgery occurred among the patients who received cefonicid as compared with those who received placebo (MantelHaenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01) (Table 4Table 4
Postoperative Infections. and Fig. 1Figure 1Percentages of Patients in the Cefonicid and Placebo Groups with Infections of Any Type, Wound Infections, and Urinary Tract Infections after Breast or Hernia Procedures.). The proportional reduction in the risk of infection was approximately the same for procedures involving the breast and for herniorrhaphies (breast procedures: risk ratio, 0.51; 95 percent confidence interval, 0.28 to 0.89; herniorrhaphies: risk ratio, 0.55; 95 percent confidence interval, 0.20 to 1.38). The reduction in risk was also evident after additional stratification according to geographic center or if infections judged to be unrelated to the surgery were included. There was no significant difference between the two groups in the average time before the diagnosis of infection; it was 11 days in the cefonicid recipients and 10 days in the placebo recipients.There were comparable reductions in the various subcategories of infections. For all wound infections, the cefonicid recipients had a risk reduction of 36 percent (MantelHaenszel risk ratio, 0.64; 95 percent confidence interval, 0.36 to 1.13; P = 0.16). This difference resulted entirely from a reduction in the number of definite infections. There were 51 percent fewer definite wound infections (MantelHaenszel risk ratio, 0.49; 95 percent confidence interval, 0.22 to 1.01; P = 0.08). Cefonicid also reduced the occurrence of purulent drainage by 57 percent (MantelHaenszel risk ratio, 0.43; 95 percent confidence interval, 0.18 to 1.00; P = 0.07) (Table 5Table 5
Selected Manifestations and Consequences.*). Putative pathogens were isolated from 22 of the 33 definite wound infections (67 percent) and from 5 of the 20 probable wound infections (25 percent). Staphylococcus aureus was the principal pathogen, accounting for 78 percent of these isolates (Table 5). The cefonicid recipients had 51 percent fewer S. aureus isolates than the placebo recipients (MantelHaenszel risk ratio, 0.49; 95 percent confidence interval, 0.18 to 1.23; P = 0.19). All S. aureus isolates from cefonicid recipients were susceptible to oxacillin, indicating that cefonicid did not select oxacillin-resistant organisms.There was no evidence of a differential effect of cefonicid in the separate types of breast-surgery procedures. For example, according to procedure, the risks of definite wound infection for cefonicid as compared with placebo were 0 of 7 versus 1 of 3 for excisional biopsy, 3 of 142 versus 7 of 142 for lumpectomy, 1 of 14 versus 0 of 16 for simple mastectomy, 6 of 122 versus 6 of 126 for modified radical mastectomy or radical mastectomy combined with axillary-node dissection, and 1 of 18 versus 4 of 15 for reduction mammoplasty (test for homogeneity, P = 0.21). None of the repeat herniorrhaphies (Table 2) resulted in infection; however, there were too few patients in this group to allow a meaningful investigation of a differential role of prophylaxis in these repeat procedures.
The cefonicid recipients also had 60 percent fewer urinary tract infections (MantelHaenszel risk ratio, 0.40; 95 percent confidence interval, 0.11 to 1.25; P = 0.18). The following bacteria were isolated from the urinary tract of placebo recipients: Escherichia coli (five patients), proteus (two), enterococcus (two), and coagulase-negative staphylococcus (one). Coagulase-negative staphylococcus was isolated from the urinary tract of two cefonicid recipients, and Pseudomonas aeruginosa and Morganella morgani were each isolated from one cefonicid recipient.
Other Outcomes
Clinically meaningful sequelae occurred after many of the infections. Eighty-seven percent of the infected patients (67 of 77) received antibiotic therapy. Eighty-three percent of the patients with a wound infection (44 of 53) made an unscheduled visit to a physician because of problems with wound healing, underwent incision and drainage, or were readmitted to the hospital. Some infections also prolonged the initial hospitalization. No serious adverse reactions were attributed to treatment with cefonicid or placebo.
The patients who received cefonicid were also less likely than those who received placebo to have had other outcomes that were probably related to postoperative infection (Fig. 2Figure 2
Percentages of Patients in the Cefonicid and Placebo Groups Who Received Postoperative Antibiotic, Had an Unscheduled Visit to a Physician for a Problem with Wound Healing, or Required Readmission for Infection or Poor Wound Healing after Breast or Hernia Procedures. and Table 5). Those who received cefonicid were 44 percent less likely to receive another antibiotic for any reason during the follow-up period (MantelHaenszel risk ratio, 0.56; 95 percent confidence interval, 0.37 to 0.85; P = 0.007), 52 percent less likely to require an unscheduled visit to a physician because of a problem with wound healing (MantelHaenszel risk ratio, 0.48; 95 percent confidence interval, 0.27 to 0.82; P = 0.009), 54 percent less likely to require an incision and drainage of the wound (MantelHaenszel risk ratio, 0.46; 95 percent confidence interval, 0.17 to 1.13; P = 0.13), and 59 percent less likely to be readmitted to the hospital because of a wound-related problem (MantelHaenszel risk ratio, 0.41; 95 percent confidence interval, 0.13 to 1.16; P = 0.15). The difference between the two groups is also evident if one considers all nonroutine visits to a physician and all readmissions rather than those caused by problems with wound healing. Among patients who did not fulfill the criteria for infection, a nonroutine visit to a physician or readmission because of a complication of wound healing was explicitly documented for 8 cefonicid recipients and 16 placebo recipients.The randomization code was broken prematurely (by opening the drug-assignment labels) for nine patients, eight of whom were included in this analysis. Of these eight, four were assigned to the cefonicid group and four to the placebo group. The following reasons were given for breaking the code prematurely: to guide therapy after a diagnosis of infection had been made (one patient in each group), to guide therapy after a suspected serious adverse reaction (one patient in each group), to replace the reconstituted drug or placebo after surgery had been postponed (two patients in the cefonicid group and one in the placebo group), and, at the surgeon's insistence, to guide intraoperative antibiotic therapy after the discovery of a pustule (one patient in the placebo group; the patient had received placebo and was given an intraoperative dose of cefazolin; no infection occurred).
Discussion
The perception that the risk of clinically important infection after clean procedures is too low to justify the use of prophylaxis is due in part to the fact that many infections become evident after the patient has left the hospital, and therefore are not detected by most surveillance systems. Seventy-five percent of the wound infections (40 of 53) we detected and 72 percent of all infections were first detected after the patients left the hospital. For the breast procedures, the risk of infection among those who received placebo in this study was 12 percent. Even the risk of infection after herniorrhaphy, 4 percent, was within the range reported in other series.12 13 14 15 The fact that a majority of infections resulted in additional medical care, including antibiotic therapy and visits to a physician, also supports the notion that these events were clinically relevant.
These data also indicate that perioperative prophylaxis was effective, preventing 48 percent of all infections — a significant difference. This trial was not designed to be powerful enough to provide separate evidence about the efficacy of prophylaxis for each of the individual procedures under investigation; however, there was no evidence of a differential effect for any of the procedures we evaluated. Thus, although the underlying risks of infection differed for these procedures, the data are most consistent with the interpretation that prophylaxis prevented the same proportion of infections for each procedure.
Similarly, although we did not design this trial to be powerful enough to study the effect of prophylaxis on a variety of component outcomes, these data show a consistent protective effect for most subsidiary measures that is of approximately the same magnitude as the overall reduction in infection. Although we believe that these additional comparisons provide useful supporting information about the efficacy of prophylaxis and reassurance that the overall effect did not result from a disproportionate effect on a small group of outcomes, the formal statistical tests of these additional comparisons should be interpreted cautiously, both because of the intentionally limited power of the design and because of problems inherent in performing multiple related-hypothesis tests.
The protective effect of prophylaxis was evident for wound infections alone. A majority of the infections in our patients were wound infections, and a majority of the wound infections were definite, according to our criteria. If noninfectious problems with wound healing were incorrectly classified as infections, the result would be to reduce the observed effect of prophylaxis. This phenomenon may explain the absence of a difference in the occurrence of probable infections and the corollary fact that the protective effect of prophylaxis was stronger for definite wound infections than for all infections. A number of definitions of wound infection have been used, ranging from purulence alone5 , 18 to very complex algorithms.19 The most recent definition proposed by the Centers for Disease Control requires purulent drainage or a positive culture or a deliberately opened wound or the physician's diagnosis.20 We chose not to rely on the presence of purulent drainage alone, since this requirement excludes some of the most threatening infections of surgical wounds. For example, one of our patients with a definite wound infection was readmitted with fever, required operative drainage of serosanguineous fluid that yielded S. aureus, and was treated with intravenous nafcillin; there was an explicit statement in the operative note that there was no frank pus. In addition, limiting the definition to purulent drainage alone does not necessarily provide a more reliable and reproducible standard, since the identification of purulence itself is potentially subjective.
Although we chose broader criteria than purulent drainage or recovery of wound pathogens for these reasons, it is noteworthy that the reduction in purulent wound infections was proportionately slightly greater than the overall effect of prophylaxis (57 percent vs. 48 percent). Similarly, there was a 50 percent reduction in the number of wounds yielding S. aureus among cefonicid recipients.
The difference between the two treatment groups in their need for postoperative interventions, including antibiotic therapy, extra visits to a physician, and readmissions, supports a clinically, as well as a biologically, important effect of prophylaxis. It also provides evidence that cefonicid's effect was not limited to trivial infections. These data indicate that the routine use of prophylaxis for the breast-surgery procedures included in the study would prevent 56 infections, including 23 definite wound infections and 16 urinary tract infections, for every 1000 patients. For herniorrhaphies, prophylaxis would prevent 19 infections, including 13 definite wound infections, per 1000 patients. We did not perform a formal cost—benefit analysis, because although hospital charges were available, costs were not. In addition, we could not obtain reliable costs for the events that occurred outside the hospital. However, if the cost of the prophylactic regimen is $10 a course, the cost of prophylaxis per infection avoided is $178 for breast procedures and $539 for herniorrhaphies. Separately, the cost per patient for each avoided readmission is $1,515 for the breast procedures and $622 for the herniorrhaphies. These costs are much lower than the usual costs of such hospitalizations.
We do not know whether other prophylactic regimens would provide as much or better prophylaxis than cefonicid. The antimicrobial spectrum of cefonicid is not markedly different from that of other agents that are commonly used for prophylaxis, although it is less active against S. aureus and is much more highly protein-bound than cefazolin, the agent most commonly used for perioperative prophylaxis. Both these factors would reduce the efficacy of cefonicid as compared with that of cefazolin. However, cefonicid's longer half-life in serum (approximately 4.5 hours as compared with 1.75 hours for cefazolin) may allow a single dose to provide better protection throughout the period of risk, presumably the time the incision is open. The duration of protection afforded by a single dose of antibiotic has not been determined explicitly. In addition, cefonicid is more resistant than cefazolin to certain staphylococcal beta-lactamases. Although cefonicid reduced the occurrence of S. aureus wound isolates by 50 percent, a proportion commensurate with its overall effect on infections, it is possible that another regimen might have prevented more such infections.
We conclude that it is appropriate to provide perioperative prophylaxis for these two types of procedures. There is little evidence for or against the use of prophylactic antibiotics for other clean surgical procedures. Nevertheless, antibiotic prophylaxis may prevent infection after procedures that cause microbial contamination and tissue injury comparable to those resulting from the procedures we studied.
Supported by a grant from Smith Kline and French Laboratories. Dr. Platt is a Burroughs Wellcome Scholar in Pharmacoepidemiology.
The study teams consisted of the following persons: Beth Israel Hospital (Boston): D.F. Zaleznik, M.D., M.B. Collins, R.N., and L. Robertson, R.N.; Brigham and Women's Hospital (Boston): R. Platt, M.D., M. Albano, R.N., S. Petrycki, R.N., and S. Fischer, R.N.; Massachusetts General Hospital (Boston): C.C. Hopkins, M.D., J.F. Burke, M.D., and P. Kelleher. R.N.; New England Deaconess Hospital (Boston): A.W. Karchmer, M.D., and M. Christensen, R.N.; Harborview Medical Center, University of Washington Hospital and Pacific Medical Center (Seattle): E.P. Dellinger, M.D., E. Dever, R.N., J. Taylor, R.N., and M. Wertz, R.N., M.S.; Baptist Medical Center and Veterans Affairs Hospital (Columbia, S.C.): C.S. Bryan. M.D., and J. Wells, P.A.; Channing Laboratory (Boston): R. Platt, M.D., S.K. Marino, M.T., K.F. Holbrook, R.N., M.R. Segal, Ph.D., T.D. Tosteson, Sc.D., A. Muñoz, Ph.D., S. Graham, and G. Campbell; and Smith Kline and French Laboratories (Philadelphia): M.A. Wikler, M.D., G. Moonsammy, and M. Jarosz.
In accordance with Journal policy, the authors have stated that Dr. Wikler, Mr. Moonsammy, and Ms. Jarosz are stockholders in and employees of Smith-Kline Beecham Ltd.
Source Information
From the Departments of Medicine and Surgery, Harvard Medical School, Boston; the Departments of Medicine and Infection Control Units, Channing Laboratory, Brigham and Women's Hospital, Beth Israel Hospital, and New England Deaconess Hospital, Boston; the Departments of Medicine and Surgery and Infection Control Unit, Massachusetts General Hospital, Boston; the Department of Surgery, University of Washington, and Harborview Medical Center, Seattle; the Department of Medicine, University of South Carolina, Columbia; and the Anti-Infective Division, Smith Kline and French Laboratories, Philadelphia. Address reprint requests to Dr. Platt at the Channing Laboratory, 180 Longwood Ave., Boston, MA 02115.
- References
References
1
Burke
Web of Science | Medline2
Kaiser
Full Text | Web of Science | Medline3
Clarke
CrossRef | Web of Science | Medline4
Hill
CrossRef | Web of Science | Medline5
Kaiser
CrossRef | Web of Science | Medline6
National Center for Health Statistics, Hospital Care Statistics Branch. 1987 Summary: National Hospital Discharge Survey. Advance data from vital and health statistics. No. 159. Hyattsville, Md.: Public Health Service, 1988. (DHHS publication no. (PHS) 88–1250.)
7
Beatty
Web of Science | Medline8
Hayes
CrossRef | Medline9
Say
Web of Science | Medline10
Tejler
CrossRef | Web of Science | Medline11
Zintel
Web of Science | Medline12
Andersen
Web of Science | Medline13
Balthazar
CrossRef | Web of Science | Medline14
Glassow
Web of Science | Medline15
Ponka
Web of Science | Medline16
StatXact™ user manual. Cambridge, Mass.: Cytel Software Corporation, 1989.
17
Armitage P. Statistical methods in medical research. Oxford: Blackwell, 1971.
18
Cruse
Web of Science | Medline19
Wilson
CrossRef | Web of Science | Medline20
Gamer
CrossRef | Web of Science | Medline
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I. Othman. (2011) Prospective randomized evaluation of prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty. Hernia 15:3, 309-313
CrossRef8
Brian V. Hogan, Mark B. Peter, Rajgopal Achuthan, Amy J. Beaumont, Fiona E. Langlands, Sara Shakes, Philip M.D. Wood, Hrishikesh G. Shenoy, Nicolas M. Orsi, Kieran Horgan, Clive R.D. Carter, Thomas A. Hughes. (2011) Perioperative Reductions in Circulating Lymphocyte Levels Predict Wound Complications After Excisional Breast Cancer Surgery. Annals of Surgery 253:2, 360-364
CrossRef9
Nihal Aydin, Muhammed Uraloğlu, Asu Deniz Yilmaz Burhanoğlu, Ömer Sensöz. (2010) A Prospective Trial on the Use of Antibiotics in Hand Surgery. Plastic and Reconstructive Surgery 126:5, 1617-1623
CrossRef10
Loveleen Thakur, Shekhar Upadhyay, Nitin J. Peters, Navdeep Saini, Michael Deodhar. (2010) Prophylactic antibiotic usage in patients undergoing inguinal mesh hernioplasty — A clinical study. Indian Journal of Surgery 72:3, 240-242
CrossRef11
David J. Leaper. (2010) Risk Factors for and Epidemiology of Surgical Site Infections. Surgical Infections 11:3, 283-287
CrossRef12
Kui-Hin Liau, Khin-Thanda Aung, Nelson Chua, Choon-Kiat Ho, Chung-Yip Chan, Alfred Kow, Arul Earnest, Sing-Joo Chia. (2010) Outcome of a Strategy To Reduce Surgical Site Infection in a Tertiary-Care Hospital. Surgical Infections 11:2, 151-159
CrossRef13
Alyssa D. Throckmorton, Judy C. Boughey, Sarah Y. Boostrom, Andrea C. Holifield, Melissa M. Stobbs, Tanya Hoskin, Larry M. Baddour, Amy C. Degnim. (2009) Postoperative Prophylactic Antibiotics and Surgical Site Infection Rates in Breast Surgery Patients. Annals of Surgical Oncology 16:9, 2464-2469
CrossRef14
Philip Pfeiffer, Signe Jørgensen, Thomas B. Kristiansen, Anna Jørgensen, Lisbet R. Hölmich. (2009) Protective Effect of Topical Antibiotics in Breast Augmentation. Plastic and Reconstructive Surgery 124:2, 629-634
CrossRef15
M. P. Simons, T. Aufenacker, M. Bay-Nielsen, J. L. Bouillot, G. Campanelli, J. Conze, D. Lange, R. Fortelny, T. Heikkinen, A. Kingsnorth, J. Kukleta, S. Morales-Conde, P. Nordin, V. Schumpelick, S. Smedberg, M. Smietanski, G. Weber, M. Miserez. (2009) European Hernia Society guidelines on the treatment of inguinal hernia in adult patients. Hernia 13:4, 343-403
CrossRef16
John P. Kirby, John E. Mazuski. (2009) Prevention of Surgical Site Infection. Surgical Clinics of North America 89:2, 365-389
CrossRef17
Edward W. Lee, Aaron C. Holtebeck, Andrew R. Harrison. (2009) Infection Rates in Outpatient Eyelid Surgery. Ophthalmic Plastic & Reconstructive Surgery 25:2, 109-110
CrossRef18
Haynes, Alex B., Weiser, Thomas G., Berry, William R., Lipsitz, Stuart R., Breizat, Abdel-Hadi S., Dellinger, E. Patchen, Herbosa, Teodoro, Joseph, Sudhir, Kibatala, Pascience L., Lapitan, Marie Carmela M., Merry, Alan F., Moorthy, Krishna, Reznick, Richard K., Taylor, Bryce, Gawande, Atul A., . (2009) A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population. New England Journal of Medicine 360:5, 491-499
Full Text19
Donald E. Fry. (2008) Preventive Systemic Antibiotics in Colorectal Surgery. Surgical Infections 9:6, 547-552
CrossRef20
Christiane Petignat, Patrick Francioli, Stephan Harbarth, Luca Regli, François Porchet, Alain Reverdin, Benedict Rilliet, Nicolas de Tribolet, André Pannatier, Didier Pittet, Giorgio Zanetti. (2008) Cefuroxime Prophylaxis Is Effective in Noninstrumented Spine Surgery. Spine 33:18, 1919-1924
CrossRef21
R. Douglas Matthews, Leigh Neumayer. (2008) Inguinal Hernia in the 21st Century: An Evidence-Based Review. Current Problems in Surgery 45:4, 261-312
CrossRef22
Ingride Richardson, Harris M. Nagler. (2008) Systemic Antibiotic Prophylaxis Not Needed for Microsurgical Varicocelectomy. Urology 71:4, 669-671
CrossRef23
A. Becker, L. Koltun, J. Sayfan. (2008) Impact of antimicrobial prophylaxis duration on wound infection in mesh repair of incisional hernia – preliminary results of a prospective randomized trial. European Surgery 40:1, 37-40
CrossRef24
Kazuhiro Ishizaka, Shinichiro Kobayashi, Tatsuya Machida, Ken-Ichiro Yoshida. (2007) Randomized prospective comparison of fosfomycin and cefotiam for prevention of postoperative infection following urological surgery. Journal of Infection and Chemotherapy 13:5, 324-331
CrossRef25
Traci L. Hedrick, Philip W. Smith, Leo M. Gazoni, Robert G. Sawyer. (2007) The Appropriate Use of Antibiotics in Surgery: A Review of Surgical Infections. Current Problems in Surgery 44:10, 635-675
CrossRef26
Penel Nicolas, Yazdanpanah Yazdan, Chauvet Marie-Pierre, Clisant Stéphanie, Giard Sylvia, Neu Jean-Charles, Lefebvre Danièle, Fournier Charles, Bonneterre Jacques. (2007) Prevention of surgical site infection after breast cancer surgery by targeted prophylaxis antibiotic in patients at high risk of surgical site infection. Journal of Surgical Oncology 96:2, 124-129
CrossRef27
Francisco Javier Sanchez-Manuel, Javier Lozano-García, Juan Luis Seco-Gil, Francisco Javier Sanchez-Manuel. 2007. Antibiotic prophylaxis for hernia repair.. .
CrossRef28
Satoko Ichikawa, Mihoko Ishihara, Tadaharu Okazaki, Kengo Warabi, Yoshifumi Kato, Satoshi Hori, Geoffrey J. Lane, Keiichi Hiramatsu, Eiichi Inada, Hiroyuki Kobayashi, Atsuyuki Yamataka. (2007) Prospective study of antibiotic protocols for managing surgical site infections in children. Journal of Pediatric Surgery 42:6, 1002-1007
CrossRef29
Soichiro Yoshida, Hitoshi Masuda, Minato Yokoyama, Tsuyoshi Kobayashi, Satoru Kawakami, Kazunori Kihara. (2007) Absence of prophylactic antibiotics in minimum incision endoscopic urological surgery (MEUS) of adrenal and renal tumors. International Journal of Urology 14:5, 384-387
CrossRef30
Angelique F. Vitug, Lisa A. Newman. (2007) Complications in Breast Surgery. Surgical Clinics of North America 87:2, 431-451
CrossRef31
D. Oertli. (2007) Lymphadenektomie der Axilla. Der Chirurg 78:3, 194-202
CrossRef32
G. Tzovaras, S. Delikoukos, G. Christodoulides, M. Spyridakis, F. Mantzos, K. Tepetes, E. Athanassiou, C. Hatzitheofilou. (2007) The role of antibiotic prophylaxis in elective tension-free mesh inguinal hernia repair: results of a single-centre prospective randomised trial. International Journal of Clinical Practice 61:2, 236-239
CrossRef33
Osvaldo Iribarren, Miguel Araujo. (2006) Effect of Antimicrobial Prophylaxis on the Incidence of Infections in Clean Surgical Wounds in Hospitals Undergoing Renovation • . Infection Control and Hospital Epidemiology 27:12, 1372-1376
CrossRef34
William J Ledger. (2006) Prophylactic antibiotics in obstetrics–gynecology: a current asset, a future liability?. Expert Review of Anti-infective Therapy 4:6, 957-964
CrossRef35
J. C. Hall, P. C. Willsher, J. L. Hall. (2006) Randomized clinical trial of single-dose antibiotic prophylaxis for non-reconstructive breast surgery. British Journal of Surgery 93:11, 1342-1346
CrossRef36
Talar Tejirian, L. Andrew DiFronzo, Philip I. Haigh. (2006) Antibiotic Prophylaxis for Preventing Wound Infection after Breast Surgery: A Systematic Review and Metaanalysis. Journal of the American College of Surgeons 203:5, 729-734
CrossRef37
Patrick Pessaux, Emilie Lermite, Eric Blezel, Simon Msika, Jean-Marie Hay, Yves Flamant, Varma Deepak, Jean-Pierre Arnaud. (2006) Predictive risk score for infection after inguinal hernia repair. The American Journal of Surgery 192:2, 165-171
CrossRef38
Angel Celdrán, Juan José Granizo. (2006) Antibiotic Prophylaxis for Hernia Repair. Journal of the American College of Surgeons 203:1, 138-139
CrossRef39
Frances Bunn, Melanie E Cunningham, Karen Handscomb, Frances Bunn. 2006. Prophylactic antibiotics to prevent surgical site infection after breast cancer surgery. .
CrossRef40
Traci L Hedrick, Melissa M Anastacio, Robert G Sawyer. (2006) Prevention of surgical site infections. Expert Review of Anti-infective Therapy 4:2, 223-233
CrossRef41
C. Terzi. (2006) Antimicrobial prophylaxis in clean surgery with special focus on inguinal hernia repair with mesh. Journal of Hospital Infection 62:4, 427-436
CrossRef42
Philip S. Barie, Soumitra R. Eachempati. (2005) Surgical Site Infections. Surgical Clinics of North America 85:6, 1115-1135
CrossRef43
Nongyao Kasatpibal, Silom Jamulitrat, Virasakdi Chongsuvivatwong. (2005) Standardized incidence rates of surgical site infection: A multicenter study in Thailand. American Journal of Infection Control 33:10, 587-594
CrossRef44
C. Terzi, D. Kılıç, T. Ünek, F. Hoşgörler, M. Füzün, G. Ergör. (2005) Single-dose oral ciprofloxacin compared with single-dose intravenous cefazolin for prophylaxis in inguinal hernia repair: a controlled randomized clinical study. Journal of Hospital Infection 60:4, 340-347
CrossRef45
Seema Biswas. (2005) Elective Inguinal Hernia Repair with Mesh: Is there a Need for Antibiotic Prophylaxis? — A Review. World Journal of Surgery 29:7, 830-836
CrossRef46
Patrick Pessaux, David Atallah, Emilie Lermite, Simon Msika, Jean-Marie Hay, Yves Flamant, Jean-Pierre Arnaud. (2005) Risk factors for prediction of surgical site infections in “clean surgery”. American Journal of Infection Control 33:5, 292-298
CrossRef47
Mehmet A. Kuzu, Selçuk Hazinedaroğlu, Şükrü Dolalan, Namık Özkan, Samet Yalçın, A. Bülent Erkek, Hatem Mahmoudi, Acar Tüzüner, Atilla H. Elhan, Ercümet Kuterdem. (2005) Prevention of Surgical Site Infection After Open Prosthetic Inguinal Hernia Repair: Efficacy of Parenteral Versus Oral Prophylaxis with Amoxicillin-Clavulanic Acid in a Randomized Clinical Trial. World Journal of Surgery 29:6, 794-799
CrossRef48
A. M. Carbonell, B. D. Matthews, D. Dreau, M. Foster, C. E. Austin, K. W. Kercher, R. F. Sing, B. T. Heniford. (2005) The susceptibility of prosthetic biomaterials to infection. Surgical Endoscopy 19:3, 430-435
CrossRef49
Leigh A. Neumayer. (2005) Invited commentary. Journal of the American College of Surgeons 200:3, 397-398
CrossRef50
David J. Joseph, Sean Bydder, Lee R. Jackson, Tammy Corica, Diana J. Hastrich, David J. Oliver, David E. Minchin, Annette Haworth, Christobel M. Saunders. (2004) Prospective trial of intraoperative radiation treatment for breast cancer. ANZ Journal of Surgery 74:12, 1043-1048
CrossRef51
FJ Sanchez-Manuel, JL Seco-Gil, Francisco Javier Sanchez-Manuel. 2004. Antibiotic prophylaxis for hernia repair. .
CrossRef52
Gregory M. Richards, Anthony M. Berson, John Rescigno, Seema Sanghavi, Beth Siegel, Deborah Axelrod, Stephanie Bernik, Vincent Scarpinato, Christopher Mills. (2004) Acute Toxicity of High-Dose-Rate Intracavitary Brachytherapy With the MammoSite Applicator in Patients With Early-Stage Breast Cancer. Annals of Surgical Oncology 11:8, 739-746
CrossRef53
E. Eason, G. Wells, G. Garber, R. Hemmings, G. Luskey, P. Gillett, M. Martin, . (2004) Antisepsis for abdominal hysterectomy: a randomised controlled trial of povidone-iodine gel. BJOG: An International Journal of Obstetrics and Gynaecology 111:7, 695-699
CrossRef54
Andrew Kingsnorth, Karl LeBlanc. (2003) Hernias: inguinal and incisional. The Lancet 362:9395, 1561-1571
CrossRef55
(2003) Questions and answers. The American Journal of Surgery 186:5, 42-43
CrossRef56
Mark A Wilson. (2003) Skin and soft-tissue infections: impact of resistant gram-positive bacteria. The American Journal of Surgery 186:5, 35-41
CrossRef57
Robert D Kugel. (2003) The Kugel repair for groin hernias. Surgical Clinics of North America 83:5, 1119-1139
CrossRef58
Donald E. Fry. (2002) The Economic Costs of Surgical Site Infection. Surgical Infections 3:s1, s37-s43
CrossRef59
Philip S. Barie. (2002) Surgical Site Infections: Epidemiology and Prevention. Surgical Infections 3:s1, s9-s21
CrossRef60
Ansgar O. Aasen, Philip S. Barie, Eugen Faist, Henri R. Ford, Donald E. Fry, Toni Hau. (2002) Panel Discussion: Current Issues in the Prevention and Management of Surgical Site Infection—Part 1. Surgical Infections 3:s1, s1-s7
CrossRef61
Gary Lawton, Hope Rasque, Stephan Ariyan. (2002) Preservation of muscle fascia to decrease lymphedema after complete axillary and ilioinguinofemoral lymphadenectomy for melanoma1 1No competing interests declared.. Journal of the American College of Surgeons 195:3, 339-351
CrossRef62
Fred G. Barker. (2002) Efficacy of Prophylactic Antibiotic Therapy in Spinal Surgery: A Meta-analysis. Neurosurgery 51:2, 391-401
CrossRef63
L.Thomas O’Connor, Marc Goldstein. (2002) Topical perioperative antibiotic prophylaxis for minor clean inguinal surgery. Journal of the American College of Surgeons 194:4, 407-410
CrossRef64
F. de Lalla. (2002) Surgical prophylaxis in practice. Journal of Hospital Infection 50, S9-S12
CrossRef65
A MELLING, B ALI, E SCOTT, D LEAPER. (2001) Effects of preoperative warming on the incidence of wound infection after clean surgery: a randomised controlled trial. The Lancet 358:9285, 876-880
CrossRef66
Mehmet A. Yerdel, Emin B. Akin, Sukru Dolalan, Ahmet G. Turkcapar, Mevlut Pehlivan, Ibrahim E. Gecim, Ercument Kuterdem. (2001) Effect of Single-Dose Prophylactic Ampicillin and Sulbactam on Wound Infection After Tension-Free Inguinal Hernia Repair With Polypropylene Mesh. Annals of Surgery 233:1, 26-33
CrossRef67
J.S. Reilly, D. Baird, R. Hill. (2001) The importance of definitions and methods in surgical wound infection audit. Journal of Hospital Infection 47:1, 64-66
CrossRef68
J.C Hall, J.L Hall. (2000) Antibiotic prophylaxis for patients undergoing breast surgery. Journal of Hospital Infection 46:3, 165-170
CrossRef69
L Gulácsi, Zs.Tatár Kiss, D.A Goldmann, W.C Huskins. (2000) Risk-adjusted infection rates in surgery: a model for outcome measurement in hospitals developing new quality improvement programmes. Journal of Hospital Infection 44:1, 43-52
CrossRef70
Edward S. Wong. (1999) The Price of a Surgical‐Site Infection: More Than Just Excess Length of Stay • . Infection Control and Hospital Epidemiology 20:11, 722-724
CrossRef71
Marin H. Kollef. (1999) EPIDEMIOLOGY AND RISK FACTORS FOR NOSOCOMIAL PNUEMONIA. Clinics in Chest Medicine 20:3, 653-670
CrossRef72
P.J. Sanderson. (1999) Assessing the role of prophylactic antibiotics in clean surgery. Journal of Hospital Infection 42:1, 7-9
CrossRef73
A. Coda, F. Botto Micca, M. Bossotti, S. Manfredi, M. Mattio, G. Ramellini, N. Canavesio, A. Bona. (1998) Reoperations for chronic infections following prosthetic hernia repair. Hernia 2:4, 163-167
CrossRef74
Jack Abrahamson. (1998) ETIOLOGY AND PATHOPHYSIOLOGY OF PRIMARY AND RECURRENT GROIN HERNIA FORMATION. Surgical Clinics of North America 78:6, 953-972
CrossRef75
Richard J Bold, Paul F Mansfield, David H Berger, Raphael E Pollock, S.Eva Singletary, Frederick C Ames, Charles M Balch, David C Hohn, Merrick I Ross. (1998) Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection. The American Journal of Surgery 176:3, 239-243
CrossRef76
Darren V. Mann, Jeremy Prout, Erik Havranek, Stuart Gould, Ara Darzi. (1998) Late-onset deep prosthetic infection following mesh repair of inguinal hernia. The American Journal of Surgery 176:1, 12-14
CrossRef77
Jeffrey R. Horwitz, Walter J. Chwals, John J. Doski, Eric A. Suescun, Henry W. Cheu, Kevin P. Lally. (1998) Pediatric Wound Infections. Annals of Surgery 227:4, 553-558
CrossRef78
Mary L. Bertin, Joseph Crowe, Steven M. Gordon. (1998) Determinants of surgical site infection after breast surgery. American Journal of Infection Control 26:1, 61-65
CrossRef79
Carol M. Ashton,, Deborah J. Del Junco,, Julianne Souchek,, Nelda P. Wray,, Carol L. Mansyur,. (1997) The Association Between the Quality of Inpatient Care and Early Readmission. Medical Care 35:10, 1044-1059
CrossRef80
Amanda Kong, Paul I. Tartter, Dana Zappetti. (1997) The Significance of Risk Factors for Infection in Patients Undergoing Lumpectomy and Axillary Dissection. The Breast Journal 3:2, 81-84
CrossRef81
L. F. Horgan, D. C. O'riordan, R. Farouk. (1997) Preliminary experience with butyl-2-cyanoacrylate adhesive in tension-free inguinal hernia repair. British Journal of Surgery 84:1, 137-138
CrossRef82
Josef E. Fischer, Patchen Dellinger. (1996) The status of anti-infectives in surgery in 1996; A roundtable discussion. The American Journal of Surgery 172:6, 49s-61s
CrossRef83
(1996) Perioperative Normothermia and Surgical-Wound Infection. New England Journal of Medicine 335:10, 747-750
Full Text84
Ronald Lee Nichols. (1996) Surgical infections: Prevention and treatment—1965 to 1995. The American Journal of Surgery 172:1, 68-74
CrossRef85
Kenneth A. Lipshy, James P. Neifeld, Russell M. Boyle, William J. Frable, Stephen Ronan, Parisa Lotfi, Harry D. Bear, J. Shelton Horsley, Walter Lawrence. (1996) Complications of mastectomy and their relationship to biopsy technique. Annals of Surgical Oncology 3:3, 290-294
CrossRef86
Matthew G. Troy, Quan-Sheng Dong, Philip B. Dobrin, David Hecht. (1996) Do topical antibiotics provide improved prophylaxis against bacterial growth in the presence of polypropylene mesh?. The American Journal of Surgery 171:4, 391-393
CrossRef87
A. Reggiori, M. Ravera, E. Cocozza, M. Andreata, F. Mukasa. (1996) Randomized study of antibiotic prophylaxis for general and gynaecological surgery from a single centre in rural Africa. British Journal of Surgery 83:3, 356-359
CrossRef88
Rick Smith, Dan Osterweil, Joseph G. Ouslander. (1996) PERIOPERATIVE CARE IN THE ELDERLY UROLOGIC PATIENT. Urologic Clinics of North America 23:1, 27-41
CrossRef89
Ronald T. Lewis, Frederick M. Weigand, Joseph Mamazza, Walter Lloyd-Smith, Donna Tataryn. (1995) Should antibiotic prophylaxis be used routinely in clean surgical procedures: A tentative yes. Surgery 118:4, 742-747
CrossRef90
Blair A. Jobe, Andrew Grasley, Karen E. Deveney, Clifford W. Deveney, Brett C. Sheppard. (1995) Clostridium difficile colitis: An increasing hospital-acquired illness. The American Journal of Surgery 169:5, 480-483
CrossRef91
S. Modena, C. Benassuti, L. Marchiori, M. Mainente, A. Zanza, G. Perus, G. Calza, G. Falezza, E. Montresor, A. Molino, G. Serio. (1995) Mastectomy and immediate breast reconstruction: Oncological considerations and evaluation of two different methods relating to 88 cases. European Journal of Surgical Oncology (EJSO) 21:1, 36-41
CrossRef92
Pl Bencini, M. Signorini, M. Galimberti, S. Cavicchini, R. Caputo. (1994) Preoperative antibiotic prophylaxis in flexural surgery of difficult contamination-prone areas of the skin: The utility of a single dose of antibiotic. Journal of Dermatological Treatment 5:1, 17-19
CrossRef93
W. S. Meijer, P. I. M. Schmitz, . (1993) Prophylactic use of cefuroxime in biliary tract surgery: Randomized controlled trial of single versus multiple dose in high-risk patients. British Journal of Surgery 80:7, 917-921
CrossRef94
William O'Brien, Per-Olof Hasselgren, Robert P. Hummel, Robert Coith, David Hyams, Lawrence Kurtzman, Henry W. Neale. (1993) Comparison of postoperative wound complications and early cancer recurrence between patients undergoing mastectomy with or without immediate breast reconstruction. The American Journal of Surgery 166:1, 1-5
CrossRef95
Gail S. Itokazu, R. A. Weinstein. (1993) Drug use in infection control — Is more less?. Infection 21:3, 135-136
CrossRef96
Edwin A. Deitch. (1992) Invited commentary. World Journal of Surgery 16:5, 964-965
CrossRef97
G. W. M. Tetteroo, J. H. T. Wagenvoort, H. A. Bruining. (1992) Role of selective decontamination in surgery. British Journal of Surgery 79:4, 300-304
CrossRef98
Wenzel, Richard P., . (1992) Preoperative Antibiotic Prophylaxis. New England Journal of Medicine 326:5, 337-339
Full Text99
D. H. Wittmann, R. E. Condon. (1991) Prophylaxis of postoperative infections. Infection 19:S6, S337-S344
CrossRef100
Adele L. Vinton, L.William Traverse, Philip C. Jolly. (1991) Wound complications after modified radical mastectomy compared with tylectomy with axillary lymph node dissection. The American Journal of Surgery 161:5, 584-588
CrossRef101
P.J. Sanderson. (1991) Prophylaxis for catheter related urinary tract infection. Journal of Hospital Infection 18:1, 1-3
CrossRef102
(1990) Antibiotic Prophylaxis for Herniorrhaphy and Breast Surgery. New England Journal of Medicine 322:26, 1884-1886
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