Research Article: 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

Date Published: July 10, 2017

Publisher: Public Library of Science

Author(s): Westyn Branch-Elliman, John E. Ripollone, William J. O’Brien, Kamal M. F. Itani, Marin L. Schweizer, Eli Perencevich, Judith Strymish, Kalpana Gupta, Mervyn Singer

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 versus 7,314/52,504 [13.9%] receiving beta-lactam alone). We found a significant association between absolute risk of AKI and receipt of combination regimens across all types of procedures. If the observed association is causal, the number needed to harm for severe AKI following cardiac surgery would be 167. The major limitation of our investigation is that it is an observational study in a predominantly male population, which may limit generalizability and lead to unmeasured confounding.ConclusionsThere are benefits but also unintended consequences of antimicrobial and infection prevention strategies aimed at “getting to zero” healthcare-associated infections. In our study, combination prophylaxis was associated with both benefits (reduction in SSIs following cardiac surgical procedures) and harms (increase in postoperative AKI). In cardiac surgery patients, the difference in risk–benefit profile by MRSA status suggests that MRSA-screening-directed prophylaxis may optimize benefits while minimizing harms in this selected population. More information about long-term outcomes and patient and societal preferences regarding risk of SSI versus risk of AKI is needed to improve clinical decision-making.

Partial Text: The optimal perioperative antimicrobial regimen for the prevention of surgical site infections (SSIs) remains an open question. The multidisciplinary Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery, a combined endorsement of the American Society of Health-System Pharmacists, Infectious Diseases Society of America, Surgical Infection Society, and the Society for Healthcare Epidemiology of America, recommends a single agent—most often a beta-lactam antibiotic—for most surgical procedures [1]. While routine use of vancomycin is not recommended, prophylaxis with vancomycin as a single agent is a consideration in methicillin-resistant Staphylococcus aureus (MRSA)–colonized patients and in institutions with a high incidence of MRSA infections [1]. A large meta-analysis suggested that beta-lactams are as effective—if not more so—than glycopeptide antibiotics, including vancomycin, in patients undergoing cardiac surgery [2].

During the period from 1 October 2008 to 30 September 2013, 70,101 eligible surgical cases at 109 unique facilities nationwide received perioperative prophylaxis with a beta-lactam only (52,504), vancomycin only (5,089), or both (12,508) (Fig 1). In total, 2,466 (3.5%) SSIs were identified across all surgical types. Preoperative MRSA colonization was identified in 2,527 (3.6%) patients. Baseline demographics are presented in Table 1.

Overall, we found that administration of combination prophylaxis was associated with a reduction in SSIs following cardiac surgical procedures, but not following other types of surgical procedures. The risk reduction in cardiac surgery after receipt of combination prophylaxis was found regardless of which single agent was the comparator and was also independent of mupirocin receipt. Preoperative MRSA colonization status affected the baseline risk of SSI and the absolute risk reduction associated with receipt of combination prophylaxis, but not the relative risk reduction associated with this strategy. Furthermore, we demonstrated that although protective against SSI for cardiac procedures, receipt of combination prophylaxis was also associated with an increase in postoperative AKI across all types of surgeries evaluated, independent of which single agent was the comparator and also independent of duration of antimicrobial prophylaxis. In other words, the increase in AKI incidence was not simply associated with the addition of vancomycin to a beta-lactam but also with the addition of a beta-lactam to vancomycin.



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