Abstract
Abstract
Background:
Pre-operative prophylactic antibiotics may decrease the frequency of surgical site infection after appendectomy. However, the optimal timing for administration of pre-operative prophylactic antibiotics is unknown. The purpose of this study was to evaluate the effect of timing of prophylactic antibiotics on the frequency of surgical site infection after appendectomy.
Methods:
Medical records were reviewed retrospectively for 577 consecutive patients who had appendectomy for acute appendicitis from 2006 to 2009. Quality assurance guidelines for timing of prophylactic antibiotics before the skin incision were changed from 0 to 30 min before the skin incision (before June 2008) to 30 to 60 min before the skin incision (after June 2008).
Results:
Surgical site infection occurred in 28 patients (4.9%). There was no difference in frequency of surgical site infection with different timing of pre-operative prophylactic antibiotic (pre-operative time 0 to 30 min: 9 infections [3.6%]; 31 to 60 min: 13 infections [5.4%]; 61 to 120 min: 5 infections [7.0%]; >120 min: 1 infection [6.6%]). Multivariable analysis showed that surgical site infection was associated significantly with medical comorbidity but not perforated appendicitis.
Conclusions:
The frequency of surgical site infection was independent of timing of preoperative prophylactic antibiotics but was associated with the presence of medical comorbidity.
S
The introduction of routine prophylactic antibiotics decreased the frequency of surgical site infection [4]. Prophylactic antibiotics are selected to target the pathogens that are cultured most commonly from the surgical procedure site. The single use of a prophylactic antibiotic such as a first- or second-generation cephalosporin, given at a maximum 2 h before surgery and continued for less than 24 h after surgery, may decrease the frequency of surgical site infection, avoid the unnecessary cost of long-term antibiotics, and minimize the development of multiple drug-resistant bacteria [5,6].
Acute appendicitis, the most common cause of acute surgical abdomen, is treated by appendectomy [7]. Although mortality is infrequent, infectious complications such as superficial surgical site infection and intra-abdominal abscess are frequent (4%–12%). However, prophylactic antibiotics may be effective in preventing postoperative infections in people who have appendectomy, whether the antibiotic is given before, during, or after surgery [8].
The optimal timing of surgical antimicrobial prophylaxis is controversial. Some studies suggested an optimal timing from 31 to 60 min before the skin incision [9]. However, others have suggested that the prophylactic antibiotic should be given less than 30 min before the skin incision [10,11]. Moreover, other reports concluded that the surgical site infection risk varies by patient and procedure factors as well as antibiotic properties but is not associated significantly with prophylactic antibiotic timing [17]. In our hospital, the Taiwan Quality Indicator Project was introduced in 2001. Furthermore, the recommended optimal timing of surgical anti-microbial prophylaxis in patients having appendectomy for acute appendicitis, previously less than 30 min before the incision, was changed in 2008 to longer time before the incision (31 to 60 min). We also changed our practice of prophylactic antibiotic for appendectomy, as directed by the quality control manager, to cefoxitin (1 to 2 g), cefmetazole (1 to 2 g), or cefazolin (1 g); gentamicin (2 mg/kg); and metronidazole (500 mg) upon induction of anesthesia [3].
The purpose of this retrospective observational study was to determine whether the change in timing of the administration of prophylactic antibiotics decreased the frequency of surgical site infection. We hypothesized that the risk of surgical site infection after appendectomy may be less when prophylactic antibiotics are given from 31 to 60 min before surgery than less 30 min before surgery.
Patients and Methods
Patients
This retrospective study reviewed all 642 consecutive patients who had appendectomy for treatment of acute appendicitis at the Department of General Surgery, Cathay General Hospital, from October 2006 to December 2009 (40 months). The optimal timing of prophylactic antibiotics recommended by the quality control manager from 2006 to May 2008 was 30 min before the surgical incision. This was changed in June 2008 to 31 to 60 min before the incision, however, actual timing of prophylactic antibiotics varied with different actual condition. The 577 patients included in the study had the pre-operative diagnosis of acute appendicitis without rupture, including patients who had ruptured appendix noted at surgery. Patients who had pre-operative diffuse peritonitis and use of therapeutic antibiotics were excluded from the study (65 patients). The study was part of the Taiwan Quality Indicator Project at Cathay General Hospital and was approved by the human subject committee of the hospital.
The prophylactic antibiotics included cefazolin, gentamicin, and metranidazole; these antibiotics usually were given for no more than 24 h (≤3 post-operative doses), but prolonged use of antibiotics was prescribed when the patient had ruptured appendix noted at operation or persistent post-operative fever. Other type antibiotics (cefoxitin or cefmetazole) were only used in 10 patients. When more than one antibiotic was administered, timing of administration was calculated as the time of any first kind of antibiotic was given. In practice, the cefazolin was always the first kind of antibiotic administrated. Surgical incisions in all patients were inspected daily during hospitalization, at the time of discharge from hospital, and at the 1-mo post-operative follow-up.
Evaluation
The medical records were reviewed retrospectively for age, gender, underlying disease, body mass index (BMI; BMI <25 or BMI ≥25), American Society of Anesthesiologists classification, type of surgery (laparoscopic or open appendectomy), medical comorbidities (cirrhosis, uremia, or diabetes mellitus), laboratory studies, prolonged antibiotics usage (duration >24 h or not), and surgical pathology results (intact or ruptured appendix). The primary outcome was the frequency of surgical site infection, as noted in the medical records, with different timing of pre-operative prophylactic antibiotics. Surgical site infections included superficial wound infection or intra-abdominal abscess. The diagnosis of intra-abdominal abscess was confirmed by abdominal and pelvic computed tomography scanning with intravenous and oral contrast.
Data analysis
Data analysis was performed with statistical software (SPSS version 15.0, IBM Corporation, Armonk, NY). For the evaluation of the association between timing of prophylactic antibiotics and frequency of surgical site infection, timing was considered in 4 groups: 0 to 30 min, 31 to 60 min, 61 to 120 min, and >120 min before the skin incision for appendectomy. The characteristics of patients with and without surgical site infection were compared with t test (continuous variables) or χ2 test (categorical variables). Variables were included in a logistic regression model for the frequency of surgical site infection, and model comparisons were based on likelihood ratio tests. All tests were two-sided, and statistical significance was defined by p≤0.05.
Results
Most patients who had appendectomy for acute appendicitis did not have medical comorbidities, surgical site infection, or re-admission within 3 mo after surgery (Table 1). The frequency of patients who had prophylactic antibiotics from 31 to 60 min before the surgical skin incision was greater in 2008 and 2009 than 2006 and 2007, but the annual frequency of surgical site infection and readmission within 3 mo after appendectomy was similar in all years of the study (Table 2). Although the guidelines for timing of prophylactic antibiotics were changed in June 2008 to 31 to 60 min before the skin incision, many patients subsequently received prophylactic antibiotics from 0 to 30 min before the skin incision (Table 2). There was no difference in frequency of surgical site infection between the groups of patients who received prophylactic antibiotics at different times before the surgical skin incision (Table 3).
Data reported as number (%) patients. Time before surgical skin incision was the time that the pre-operative prophylactic antibiotics were given.
BMI, body mass index.
Data reported as number (%) patients.
Data reported as number (%) patients or odds ratio (95% confidence interval).
Univariate analysis showed that the frequency of surgical site infection was affected significantly by the presence of medical comorbidities and ruptured appendix (Table 4). However, in multivariable analysis, the frequency of surgical site infection was affected significantly by the presence of medical comorbidities but not ruptured appendix (Table 4).
n=577 patients.
BMI=body mass index.
Discussion
The present study showed that the timing of pre-operative prophylactic antibiotics did not affect the frequency of surgical site infection after appendectomy for acute appendicitis. Therefore, the optimal timing of antibiotic prophylaxis may be from 0 to 30 min or 31 to 60 min before the surgical skin incision. A previous study suggested that the prophylactic antibiotic should be given less than 2 h before the incision, but the National Surgical Infection Prevention Project recommended that the antibiotic should be given as close to the incision time as possible to decrease the frequency of surgical site infection [5,6]. Another study suggested that an antibiotic may be more effective when given from 30 to 59 min than 0 to 30 min before the incision [9]. A previous review suggested that prophylactic antibiotics for appendectomy given 2 h before the incision may decrease the frequency of infection [8]. The present study evaluated only appendectomy for acute appendicitis. Therefore, the effects of different types of surgery and diseases may be less in the present study than studies that evaluated varied surgical conditions.
During the first 2 y of the present study, when the recommended timing of prophylactic antibiotics was within 30 min before surgery, compliance with the timing recommendation was high (Table 2). In the latter 2 y of the study, when the timing recommendation was changed, there was less compliance with the recommendation to give the antibiotics from 31 to 60 min before the skin incision (Table 2). In another study, when the timing of prophylactic antibiotics was changed to less than 60 min, 95% compliance was achieved [12]. Achieving compliance to within 60 min may be less difficult than recommendations with a tighter, 30 min timing interval, because it may be difficult to accurately predict in advance the exact incision time. In our practice, when the recommended timing was 0 to 30 min before the incision, the antibiotic was given intravenously immediately after induction of general anesthesia or just before the incision. This was more easily controlled by the medical staff rather than an earlier timing set at 31 to 60 min before the incision. Other reports have reported a similar difficulty for surgeons and anesthesiologists in the United States and Europe to start drugs during the 60 min before the start of surgery [4,5,13].
Intravenous administration of cefazolin immediately before the induction of anesthesia (average, 17 min before the skin incision) may provide better serum and tissue levels [14]. The most common bacteria cultured from the surgical wounds were Escherichia coli and other clones from the colon and not skin (data not shown). This contamination may have occurred after the skin incision when the inflamed appendix was approached or removed. Another study showed that the risk of infection in clean contaminated cases increases when the bowel is transected [15]. Therefore, the optimal timing of prophylactic antibiotic administration may be affected more by the time when the inflamed appendix is removed than the time of the initial skin incision.
Changing the timing guideline did not cause any improvement in the frequency of surgical site infection after appendectomy for acute appendicitis. Therefore, the timing guideline might not be an effective method for quality improvement. Mandatory quality control reporting without proven improvement or strong evidence may cause skepticism and limited compliance with quality improvement campaigns [16].
Despite the present study, the optimal timing of prophylactic antibiotics for acute appendicitis remains controversial. The change in recommended timing of prophylactic antibiotic administration did not lower the surgical site infection rate.
Footnotes
Author Disclosure Statement
No competing financial interests exist.