Infection Control & Hospital Epidemiology (2019), 40, 142–149 doi:10.1017/ice.2018.286


Original Article


Cefazolin as surgical antimicrobial prophylaxis in hysterectomy: A systematic review and meta-analysis of randomized controlled trials


Aurora Pop-Vicas MD, MPH1, Stephen Johnson MLS2 and Nasia Safdar MD, PhD1,3 1Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, 2Ebling Library for


the Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin and 3William S. Middleton Memorial Veterans Affairs Hospital, Madison, Wisconsin


Abstract


Objective: Current practice guidelines recommend cefazolin, cefoxitin, cefotetan, or ampicillin-sulbactam as first-line antibiotic prophylaxis in hysterectomy. We undertook this systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether cefazolin, with limited antianaerobic spectrum, is as effective in preventing surgical site-infection (SSI) as the other first- choice antimicrobials that have more extensive antianaerobic activity. Methods: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for relevant randomized controlled trials (RCT) in any language up to January 23, 2018. We only included trials that measured SSI (our primary outcome) defined as superficial, deep, or organ space. We excluded trials of β-lactams no longer in clinical use. Results: In terms of SSI incidence, cefazolin use was not inferior to its comparator in 12 of 13 individual RCTs included in the analysis. The meta-analysis summary estimate showed a significantly higher SSI risk with cefazolin versus cefoxitin or cefotetan (risk ratio, 1.7; 95% CI, 1.04–2.77; P=.03). However, most studies included nonstandardized dosing and duration of antimicrobial prophylaxis, had indeterminate or high risk of bias, did not include patients with gynecological malignancies, and/or were older RCTs not reflective of current clinical practices. Conclusion: Due to inherent limitations associated with old RCTs with limited relevance to contemporary surgery, an RCT of cefazolin versus regimens with significant antianaerobic spectrum is needed to establish the optimal choice for SSI prevention in hysterectomy.


(Received 28 June 2018; accepted 27 September 2018; electronically published 5 December 2018)


Surgical site infections (SSIs) are the most common and costly healthcare-associated infections (HAIs). In the United States, ~160,000–300,000 SSIs occur each year, with annual healthcare costs of $3.5–$10 billion.1 The prevention of SSI is increasingly important as the number of surgical procedures performed in the United States continues to rise. The Centers for Disease Control and Prevention (CDC) estimates that approximately half of SSIs are preventable using evidence-based strategies.2 In addition, SSI prevention is recognized by healthcare organizations, payers, and governmental agencies, including the Centers for Medicaid and Medicare Services, as a national patient safety priority, with hospital performance tied to reimbursement.3 For more than 20 years, the medical literature has documented


that the appropriate perioperative prophylactic use of anti- microbial agents can reduce the incidence of postoperative SSI.4–6 Hysterectomies are among the most prevalent surgical procedures


Author for correspondence: Aurora Pop-Vicas, MD, MPH, Department ofMedicine,


University of Wisconsin School of Medicine and Public Health, 1685 Highland Ave, 5th floor, Madison, WI 53705. E-mail: popvicas@medicine.wisc.edu


Cite this article: Pop-Vicas A, et al. (2019). Cefazolin as surgical antimicrobial


prophylaxis in hysterectomy: A systematic review and meta-analysis of randomized controlled trials. Infection Control & Hospital Epidemiology 2019, 40, 142–149. doi: 10.1017/ice.2018.286


© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved.


in United States, performed in>600,000 women each year. Among them, up to 2% are complicated by SSI,1 and these are associated with longer hospital stays, higher risk of readmission,7 and an additional $5,000 in healthcare costs for each hysterectomy-related infection.7 According to the American College of Obstetricians and Gynecologists (ACOG) practice guidelines, women undergoing abdominal or vaginal hyster- ectomy should receive a preoperative, single-dose antimicrobial.8 This recommendation is evidence-based and has been established by randomized placebo-controlled trials (RCTs) in which timely administration of preoperative antibiotics has shown significant SSI reductions in patients undergoing hysterectomy.9,10 Cephalosporins are the most thoroughly studied antimicrobial prophylaxis agents. These drugs are effective against many gram- positive and gram-negative microorganisms. They also share the features of demonstrated safety, acceptable pharmacokinetics, and a reasonable cost per dose.6 In particular, cefazolin is widely used and is generally viewed as the prophylactic guideline- recommended antimicrobial agent of first choice for abdominal or vaginal hysterectomy.8,11 Antibiotics with broader spectrum, including more extensive antianaerobic activity, such as cefotetan, cefoxitin, or ampicillin-sulbactam, are also first-line recom- mended options. Head-to-head comparative data between these


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