Infection Control & Hospital Epidemiology
antibiotics and cefazolin in terms of efficacy in SSI prevention for women undergoing hysterectomy are scarce, and it remains unclear whether the added antianaerobic spectrum provides a prophylactic advantage. This issue is important from the stand- point of antibiotic stewardship and the desire to use the narrowest-spectrum antibiotic indicated. Therefore, we undertook a meta-analysis to examine the efficacy of cefazolin compared with other antimicrobials for prevention of SSI in women undergoing hysterectomy, focusing specifically on agents with broad antianaerobic activity.
Methods Search strategy
We conducted our study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.12 We searched PubMed (including MED- LINE), Scopus, Web of Science, Cochrane Central databases, EMBASE, and abstracts fromrelevant proceedings and conferences through January 23, 2018, without restrictions to language or date range. We manually reviewed the references of systematic reviews and meta-analyses previously published on this topic to identify additional eligible studies. A librarian (S.J.) assisted with the literature search. To identify eligible studies, we used the following medical subject headings with the “AND” function: cephalosporins, surgical wound infection, hysterectomy, clinical trials.We used the following keywords (text words) with the “OR” function: antibiotic prophylaxis, cefazolin, postoperative, postsurgical, infection, complications, and random allocation.
Inclusion criteria
We included RCTs comparing cefazolin (any dose) with other systemic antimicrobials administered as surgical prophylaxis agents in women undergoing abdominal and/or vaginal hyster- ectomy. To be included, studies had to provide information on the primary outcome and calculation of a risk ratio. We excluded studies of antimicrobial agents that are no longer manufactured or clinically used in the United States for surgical antimicrobial prophylaxis.
Outcome definitions
Our primary outcome of interest was SSI, as defined by CDC criteria.6 As such, we included studies where the reported primary or secondary outcome was described in terms consistent with this definition, despite slight changes in terminology over time. Therefore, we considered the following reported outcomes as consistent with SSI: wound infection, vaginal cuff infection, pelvic infection, infected hematoma, deep pelvic abscess, abdominal wound infection, surgical wound infection, and postoperative skin and soft-tissue infection. Although “febrile morbidity” is a clinical outcome frequently reported in older trials of antimicrobial prophylaxis, we did not include it into our study because the relationship with SSI versus other postoperative etiologies cannot be precisely determined.
Data extraction and assessment of study quality and risk of bias
We abstracted data on study setting, sample size, indications for surgery (benign and/or malignant), type of surgery (abdominal
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and/or vaginal hysterectomy), prophylactic antibiotic used (dose and duration), duration of follow up, loss to follow up, and incidence of SSI. We assessed risk of bias using the GRADE guidelines for randomized controlled trials.13 We assigned a rating of high risk of bias if fewer 4 of the GRADE criteria were fulfilled, an indeterminate risk of bias if information on at least 3 of the GRADE criteria were not specified, and a low risk of bias if 4 or more of the 7 GRADE criteria were fulfilled. One author (A.P.V.) abstracted the data; each report was identified by the search strategy described above and independently reviewed by a second author (N.S.). Disagreements regarding data extraction, risk of bias assessment, and study inclusion were resolved by discussion among the authors.
Statistical analysis
We performed meta-analyses to obtain pooled estimates of the risk ratio (RR) and 95% confidence interval (CI) for SSI associated with cefazolin versus other antimicrobials.We conducted subgroup analyses for abdominal versus vaginal hysterectomies and for dif- ferent groups of comparison antimicrobials. We used the I2 test to assess the SSI estimates that could be attributed to study hetero- geneity,14 and we conducted fixed-effects meta-analysis for I2<25%, and random effects model for I2>25%. We assessed publication bias using a funnel plot and the Eggers statistical test.15,16 We analyzed statistical data with Comprehensive Meta- Analysis (CMA) version 2.0 software (Biostat, Englewood, NJ).
Results Study selection
Figure 1 shows our review process for study selection. After de- duplication, we screened the titles and/or abstracts of 418 unique references for eligibility; of these, we reviewed 40 full-text articles, and ultimately included 13 studies in the review and meta- analyses. The main reasons for study exclusion were comparator antimicrobials no longer manufactured or clinically used in the United States (n=12); primary outcome of interest (ie, SSI) not reported (n=3); gynecological surgeries other than hyster- ectomies (n=2); and other reasons (n=10) (Fig. 1).
Study and patient population characteristics
The characteristics of the 13 RCTs are presented in Table 1. Most studies were conducted during 1979–2003, with only 2 studies performed within the last 10 years. Publication languages inclu- ded English in 12 studies and Italian in 1 study.17 Most of the studies enrolled women undergoing hysterectomies in university- affiliated hospitals within United States (5 trials), Europe (4 trials), Asia (3 trials), and Canada (1 trial). None of the trials included laparoscopic surgeries. Nine studies reported the indi- cations for hysterectomy, which included primarily benign gynecological conditions. One study included 2 patients with endometrial carcinoma,17 and 2 other studies mentioned the inclusion of 17%–20% patients with neoplastic disease, not otherwise specified.18,19 Abdominal hysterectomy, vaginal hysterectomy, or both were
performed in 3, 3, and 7 studies, respectively (3,528 total patients). The overall SSI rates for abdominal and vaginal hysterectomy were 5.5% and 3%, respectively. One study20 included gynecological
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