Antimicrobial prophylaxis for colorectal surgery
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
A systematic review is undertaken to assess the relevant literature and to establish the effectiveness of antimicrobial prophylaxis in patients undergoing colorectal surgery for the prevention of surgical wound infection (SWI).
The review addresses the following questions:
1 Does antibiotic prophylaxis diminish the risk of SWI in colorectal surgery.
2 What spectrum of bacteria (aerobes or anaerobes) needs to be addressed by antibiotic choice.
3 What is the best timing of antibiotic administration, specifically, should antibiotics be continued into the post operative period.
4 What route of antibiotic administration (intravenous, oral or both) is most effective in preventing SWI.
5 Does any antibiotic choice exceed the efficacy of currently recommended gold standard prophylactic antibiotic therapy ‐ for definitions see 'Methods of the review'.
Background
Abdominal surgical wound infection (SWI) in patients having operations on the large intestine occurs frequently in those who do not receive antibiotic prophylaxis, in about 40% of patients (Baum 1981). When an infection does occur, it often involves more than the simple drainage of subcutaneous pus and home dressing changes. The risk of death is twice as high when surgical wound infection occurs (relative risk (RR) 2.2, 95% confidence interval (CI) 1.1 to 4.5), intensive care unit admission is more likely (RR 1.6, 95% CI 1.3 to 2.0) and hospital stay lengthened on the average by five days (Kirkland 1999). An average of $6200 in home care costs are incurred after discharge (in 2004 U.S. dollars) (Smith 2004), and the risk of hospital readmission is greatly increased in patients with SWI (RR 5.5, 95% CI 4.0 to 7.7) (Kirkland 1999). Contrary to adages about laudable pus, survival from cancer in patients having colon cancer removed even seems, for uncertain reasons, to be diminished when wound infection has occurred (Nespoli 2004). So, whatever can be done to lessen the risk of surgical wound infection is clearly a priority in patient safety and cost containment of medical care. In 1981, an early systematic review that compared wound infection risk in patients receiving antibiotic prophylaxis to those randomised to placebo or no treatment found that infection risk was so diminished that it was stated clearly at the end that studies that included no treatment controls in this field were no longer ethical (Baum 1981). It was also stated that gold standard antibiotic choices should be established so that in all future studies one arm of the study include that gold standard as the acceptable benchmark from which to judge the new antibiotic. Since then guidelines have been developed a suggested optimal antibiotic choice and dosage regimens published (MedicalLetter 2004). Yet a recent survey of American hospitals found that these guidelines are followed only about half the time (Bratzler 2005). Also there is little evidence that the published guidelines have been developed as a result of a thorough review of all the available evidence. The Medical Letter's guidelines for antibiotic prophylaxis are neither referenced nor signed (MedicalLetter 2004).
Published distillations of evidence are found in three meta‐analyses. The first, cited above, dealt only with any antibiotic versus no treatment controls (Baum 1981). The second looked only at one aspect of route of administration: oral plus intravenous antibiotics versus intravenous antibiotics alone (Lewis 2002). The third was a global review of studies published from 1984 to 1997, but it focussed more on individual comparisons than the global issues mentioned above (Song 1998). In order to determine if evidence exists to confirm the need for antibiotic prophylaxis (again), to determine what spectrum of bacteria need to be addressed by antibiotic choice (e.g gram negative versus gram positive bacteria) , to determine the best timing and route of antibiotic administration and finally to see if any antibiotic choice exceeds the efficacy of currently recommended published guidelines, this systematic review is undertaken.
Objectives
A systematic review is undertaken to assess the relevant literature and to establish the effectiveness of antimicrobial prophylaxis in patients undergoing colorectal surgery for the prevention of surgical wound infection (SWI).
The review addresses the following questions:
1 Does antibiotic prophylaxis diminish the risk of SWI in colorectal surgery.
2 What spectrum of bacteria (aerobes or anaerobes) needs to be addressed by antibiotic choice.
3 What is the best timing of antibiotic administration, specifically, should antibiotics be continued into the post operative period.
4 What route of antibiotic administration (intravenous, oral or both) is most effective in preventing SWI.
5 Does any antibiotic choice exceed the efficacy of currently recommended gold standard prophylactic antibiotic therapy ‐ for definitions see 'Methods of the review'.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials that assess the effectiveness of antimicrobial prophylaxis in the prevention of postoperative surgical wound infections in patients undergoing colorectal surgery.
Types of participants
Patients undergoing either elective or emergency colorectal surgery.
Types of interventions
All antimicrobial prophylaxis regimens used to prevent postoperative infection are considered. The antibiotics must be administered before the onset of infection. For example studies using antibiotics given before surgery for suspected appendicitis or diverticulitis are excluded as in these instances the antibiotics are being given for an established infection for which surgery is being done.
Types of outcome measures
The abdominal wound itself has the greatest risk of infection, most commonly from endogenous colorectal bacterial contamination during surgical procedures (Pollock 1987). In this review, therefore, the rate of surgical wound infection was used as the outcome measure to assess the relative effectiveness of antimicrobial prophylaxis in colorectal surgery. The definition and diagnosis of surgical wound infections often vary in published studies, but with the common feature of pus expressed from the surgical incision. Only abdominal wound infections were included because they are more reliably identified than, for example, perineal infections.
Search methods for identification of studies
The original search was conducted as part of an NHS R&D Health Technology Assessment project (Song 1998). A literature search of MEDLINE (1980‐ through 2006), EMBASE /EMBASE Alert, and the Cochrane Controlled Trials Register were conducted with the assistance of the NHS CRD Information Services. The titles and abstracts of hits were assessed and copies of relevant studies collected. The references of retrieved articles were checked to locate other relevant trials. In addition, a sample of several key journals were hand searched in addition to the electronic database searches. Studies in all languages were considered.
The full search strategy is available in the original publication (Song 1998). Key words used in the search strategy included:
Surgical Wound Infection
Postoperative Complications
Premedication
Bacterial Infections
Infection
Sepsis
Anti‐Infective Agents
Antibiotic$
Antimicro$
Colon and rectal surgery
Anastomosis, surgical
Colectomy
Enterostomy
Colostomy
Ileostomy
Anastomosis
Abdomen$
Initially the start date of 1984 was chosen because activity in this field at this time included the introduction of many new antibiotics, changes in the clinical use of antibiotic prophylaxis, improvement in surgical procedures, possible emergence of antibiotic‐resistant micro‐organisms, and the large volume of literature on this topic. When updating the review, it was considered sensible to extend the search period to include trials published from 1980 onwards. This was to ensure trials published subsequent to a previous review of clinical trials of antimicrobial prophylaxis in colon surgery (Baum 1981) were included. The search, therefore, is updated to cover 1980 ‐ through 2006)
Data collection and analysis
Due to the enormous number of studies published in this area, once the decision has been made to include a study, the methodological quality (validity) of the study was assessed by one reviewer (AMG or FS for the original 1998 report and RN for this review, and checked by another (AMG or FS from the original report and AMG for this review) using the following check‐points;
‐Was the assignment to the treatment groups really random (vs. quasi randomization such as birth dates or hospital numbers)?
‐Were those assessing outcomes blind to the treatment allocation?
‐Were the control and treatment groups comparable at entry, i.e.were there significant differences in clincal parameters such as age/gender/diagnosis?
‐Were the groups treated identically other than for the named interventions?
‐Were the operative procedures defined and described?
‐Was the written definition of wound infection and other outcome measures included?
‐Was relatively complete follow‐up (>90%) achieved?
‐Were the outcomes of people who withdrew described and included in the analysis?
Any disagreements arising at this stage were resolved by discussion.
Data Abstraction
Data were extracted from included trials by one reviewer and checked by another using a data‐abstraction form.
Data Synthesis
Studies were grouped according to the following comparisons:
·Antimicrobial prophylaxis versus no treatment control or placebo
·Short versus long term use of an antimicrobial (either alone or in combination), that is a single pre‐operative dose versus extension of antibiotic coverage into the post operative period. A sub‐group analysis included patients receiving a single pre‐op dose versus those receiving a second intra‐operative dose of antibiotic if the operative procedure extended beyond the half life of the origincal antibiotic dose.
·Any antimicrobial prophylaxis regimen with added aerobic bacterial coverage versus same regimen with no additional aerobic coverage
·Any antimicrobial prophylaxis regimen with added anaerobic bacterial coverage versus same regimen with no additional anaerobic coverage
In each of these previous 2 comparisons, the primary (non‐test) antibiotic may have a bacterial coverage spectrum that might overlap with the test antibiotic. Sensitivity analyses will be done when such overlap does not occur ‐ for instance selecting studies in which an aminoglycoside (with no anaerobic bacterial coverage) is given plus or minus metronidazole for its anaerobic bacterial coverage.
·Antimicrobial prophylaxis administered orally or intravenously.
·Combined oral and intravenous antibiotic prophylaxis versus either oral or intravenous antibiotic prophylaxis alone.
·Comparison of any antibiotic therapy to an established Gold Standard antibiotic prophylaxis regimen. This is in concordance with the recommendation of (Baum 1981), that once the efficacy of any antibiotic prophylaxis was established, as it was in 1980, when compared to placebo, then all future antibiotic trials consist of comparisons of trial antibiotics to what was referred to as Gold Standards, those antibiotics in common clinical use as recommended by widely accepted published clinical guidelines, and so see if any antibiotic regimen clearly exceeds the efficacy of widely recommended choices, and therefore may be worthy of further study, or alternatively if a regimen is so much worse than established choices as to recommended it s non‐use.
The Gold Standards used in these comparisons include:
Oral Neomycin/Erythromycin Base (MedicalLetter 2004)
Intravenous Cefoxitin (MedicalLetter 2004)
Intravenous and oral Doxycycline (Andaker 1992)
These three options are recommended either by the Medical Letter or in a series of Scandinavian studies.
Heterogeneity will be examined. Firstly a check is to be made for clinical heterogeneity by examining characteristics in the table of included studies. Statistical heterogeneity will be assessed using the chi‐square test (p<0.1) and by assessing the I2 statistic (this describes the percentage of the variability in effect estimates that is due to heterogeneity rather than chance). If heterogeneity exists, this will be investigated through sub‐grouping.
If pooling is felt to be reasonable then the random effects method will be used.
The dichotomous outcome (e.g SWI: present or not) is to be presented as relative risks (RR) with 95% confidence intervals (CI).
