The combined use of vancomycin and a beta-lactam antibiotic for prophylaxis against surgical site infections is associated with both benefits and harms, according to findings from a national propensity-score–adjusted retrospective cohort study.

For example, the combination treatment reduced surgical site infections (SSIs) 30 days after cardiac surgical procedures but increased the risk of postoperative acute kidney injury (AKI) in some patients, Westyn Branch-Elliman, MD, of the VA Boston Healthcare System and her colleagues reported online July 10 in PLOS Medicine.

Magnified 20,000X, this colorized scanning electron micrograph depicts a grouping of MRSA bacteria.

Of 70,101 cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures performed between Oct. 1, 2008, and Sept. 30, 2013, in a multicenter, national VA cohort, 52,504 involved use of beta-lactam–only prophylaxis, 5,089 involved vancomycin-only prophylaxis, and 12,508 involved prophylaxis with a combination of the two. There were 2,466 surgical site infections at 109 medical centers.

Among cardiac surgery patients, the incidence of surgical site infections was significantly lower for the 6,953 patients treated with both drugs vs. the 12,834 treated with a single agent (0.95% vs. 1.48%), the investigators found (PLOS Med. 2017 Jul 10. doi: 10.1371/journal.pmed.1002340).

SSI benefit with combination therapy

“After controlling for age, diabetes, ASA [American Society of Anesthesiologists] score, mupirocin administration, current smoking status, and preoperative MRSA [methicillin-resistant Staphylococcus aureus] colonization status, receipt of combination antimicrobial prophylaxis was associated with reduced SSI risk following cardiac surgical procedures (adjusted risk ratio, 0.61),” they wrote, noting that, when combination therapy was compared with either of the agents alone, the associations were similar and that no association between SSI reduction and the combination regimen was seen for the other types of surgical procedures assessed.

Secondary analyses showed that, among the cardiac patients, differences in the rates of SSIs were seen based on MRSA status in patients undergoing cardiac surgery. Among MRSA-colonized patients, SSIs occurred in 8 of 346 patients (2.3%) who received combination prophylaxis vs. 4 of 100 patients (4%) who received vancomycin alone (aRR, 0.53), and, among MRSA-negative and MRSA-unknown cardiac surgery patients, SSIs occurred in 58 of 6,607 patients (0.88%) receiving combination prophylaxis and 146 of 10,215 patients (1.4%) receiving a beta-lactam alone (aRR, 0.60).

“Among MRSA-colonized patients undergoing cardiac surgery, the associated absolute risk reduction for SSI was approximately triple that of the absolute risk reduction in MRSA-negative or -unknown patients, with a [number needed to treat] to prevent 1 SSI of 53 for the MRSA-colonized group, compared with 176 for the MRSA-negative or -unknown groups,” they wrote.

The incidence of Clostridium difficile infection was similar in both exposure groups (0.72% and 0.81% with combination and single agent prophylaxis, respectively).

Higher AKI risk with combination therapy

“In contrast, combination versus single prophylaxis was associated with higher relative risk of AKI in the 7-day postoperative period after adjusting for prophylaxis regimen duration, age, diabetes, ASA score, and smoking,” they said.

The rate of AKI was 23.75% among patients receiving combination prophylaxis, compared with 20.79% and 13.93% among those receiving vancomycin alone and a beta-lactam alone, respectively.

Significant associations between absolute risk of AKI and receipt of combination regimens were seen across all types of procedures, the investigators said.

“Overall, the NNH [number needed to harm] to cause one episode of AKI in cardiac surgery patients receiving combination therapy was 22, and, for stage 3 AKI, 167. The NNH associated with one additional episode of any postoperative AKI after receipt of combination therapy was 76 following orthopedic procedures and 25 following vascular surgical procedures,” they said.

The optimal approach for preventing SSIs is unclear. Although the multidisciplinary Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery recommend single agent prophylaxis most often, with a beta-lactam antibiotic, for most surgical procedures, the use of vancomycin alone is a consideration in MRSA-colonized patients and in centers with a high MRSA incidence, and combination prophylaxis with a beta-lactam plus vancomycin is increasing. However, the relative risks and benefit of this strategy have not been carefully studied, the investigators said.

Thus, the investigators used a propensity-adjusted, log-binomial regression model stratified by type of surgical procedure among the cases identified in the Veterans Affairs cohort to assess the association between SSIs and receipt of combination prophylaxis versus single agent prophylaxis.

Though limited by the observational study design and by factors such as a predominantly male and slightly older and more rural population, the findings suggest that “clinicians may need to individualize prophylaxis strategy based on patient-specific factors that influence the risk-versus-benefit equation,” they said, concluding that “future studies are needed to evaluate the utility of MRSA screening protocols for optimizing and individualizing surgical prophylaxis regimen.”

This study was funded by Veterans Affairs Health Services Research and Development. Dr. Branch-Elliman reported having no disclosures. One other author, Eli Perencevich, MD, received an investigator initiated Grant from Merck Pharmaceuticals in 2013.

sworcester@frontlinemedcom.com

VA cohort study: Individualize SSI prophylaxis based on patient factors