Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study

Abstract

BackgroundThe optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered.Methods and findingsUsing a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between receipt of combination prophylaxis and SSI was found for the other types of surgeries evaluated, including orthopedic joint replacement procedures. In MRSA-colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%) patients who received combination prophylaxis versus 4/100 (4.0%) patients who received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these associations, the number needed to treat to prevent 1 SSI in MRSA-colonized patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI incidence was similar in both exposure groups. Across all types of surgical procedures, risk of AKI was increased in the combination antimicrobial prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089 [20.8%] receiving vancomycin alone...

Meta‐analysis of oral antibiotics, in combination with preoperative intravenous antibiotics and mechanical bowel preparation the day before surgery, compared with intravenous antibiotics and mechanical bowel preparation alone to reduce surgical‐site infections in elective colorectal surgery

“…At present, in the USA and Canada, around 40 per cent of patients are given oral antibiotics in combination with MBP6. The combination of oral neomycin and erythromycin has been recommended for use as preoperative antibiotic prophylaxis for colorectal surgery in an advisory statement from the Medicare National Surgical Infection Prevention Project35.…”

“…The reasons for avoidance of MBP in Europe are multifactorial, but the trend towards enhanced recovery after surgery (ERAS) protocols that exclude routine MBP is probably a significant contributor5. Concerns regarding hospital‐acquired infections including Clostridium difficile are relevant only when patients are exposed to extended bowel‐cleansing protocols6. The aim of this review was to assess only trials that included 1 day of preoperative antibiotics, and all trials assessing longer periods of preoperative antibiotic exposure were excluded.…”

Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens

“…Patients who have had this major surgery are at risk for certain severe postoperative infections. It has been reported that the incidence of sternal surgical site infections after open heart surgery ranges from 1.3 to 8.6% (1,2), and the incidence of deep sternal infections, such as mediastinitis, is 4.6% (2). Furthermore, the 1-year mortality rate increases for patients with deep sternal infections to reach ϳ22% (3).…”

Preoperative antibiotics and cardiovascular implantable electronic device infection: A cohort study in veterans

“…reported in a national VA cohort that patients who received vancomycin as a preoperative prophylaxis had an increased risk of postoperative acute kidney injury. Moreover, the rate of vancomycin use as preoperative antibiotic in patients who underwent cardiac (bypass procedures, valve repairs, and repair of structural heart disease) procedures; orthopedic joint replacement; or vascular, colorectal, or hysterectomy procedures ranged up to 25% . Courtney et al.…”

“…Nevertheless, Branch-Elliman et al reported in a national VA cohort that patients who received vancomycin as a preoperative prophylaxis had an increased risk of postoperative acute kidney injury. Moreover, the rate of vancomycin use as preoperative antibiotic in patients who underwent cardiac (bypass procedures, valve repairs, and repair of structural heart disease) procedures; orthopedic joint replacement; or vascular, colorectal, or hysterectomy procedures ranged up to 25% 36. Courtney et al also showed that patients who received combined vancomycin and cefazolin as prophylaxis for primary joint arthroplasty had a significantly higher risk of acute kidney injury as compared to patients who received cefazolin alone 22.…”