By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
SYNOPSIS: A retrospective cohort study of adults who underwent an elective craniotomy, hip replacement, knee replacement, spinal procedure, or hernia repair found only 59% adhered to recommended guidelines on prophylactic antibiotic prescribing. Unnecessary vancomycin use was the most common reason for nonadherence and had 19 times higher risk for acute kidney injury.
SOURCE: Cabral SM, Harris AD, Cosgrove SE, et al. Adherence to antimicrobial prophylaxis guidelines for elective surgeries across 825 United States hospitals, 2019-2020. Clin Infect Dis 2023; Feb. 12: ciad077. doi: 10.1093/cid/ciad077. [Online ahead of print].
A postoperative infection is a dreaded complication for patients, providers, and the healthcare system. Prophylactic antibiotics are crucial for preventing postoperative infections. They have allowed elective surgery, which once was a very risky endeavor in the pre-antibiotic era, to become part of routine medical practice. Yet, the risks of antibiotic overuse, such as increasing the spread of antimicrobial resistance, adverse drug reactions, and Clostridioides difficile infection, are well recognized. Cabral and colleagues sought to ascertain compliance with current perioperative antibiotic guidelines and to assess the impact of the COVID-19 pandemic on perioperative antibiotic use.
The study was a retrospective cohort analysis of adults who underwent elective craniotomy, hip replacement, knee replacement, spinal procedure, or hernia repair. These procedures were chosen based on antimicrobial stewardship relevance and having a Grade A strength of evidence rating in the American Society of Health-System Pharmacists (ASHP) 2013 surgical antimicrobial prophylaxis guidelines. The investigators collected patient information from a large payer database that included claims and clinical data from more than 870 million U.S. hospital encounters. Those patients included were at least 18 years of age, underwent one of the five procedures listed earlier, had an elective admission as opposed to a trauma or emergency admission, and had a discharge date on or between Jan. 1, 2019, and Dec. 31, 2020. Those who underwent multiple procedures on day 1 or did not receive antibiotics on day 1 were excluded. The prophylactic regimen was defined as any antimicrobial administered on hospital day 1 (i.e., the day of surgery).
The primary outcome was adherence (defined as yes/no) to the antimicrobial agent(s) recommended by the ASHP guidelines. Cefazolin monotherapy was the only adherent regimen for most patients. Alternative regimens were permitted for patients with known methicillin-resistant Staphylococcus aureus (MRSA) colonization, at high risk for MRSA colonization, or with β-lactam allergies. Thus, the addition of vancomycin to cefazolin was permitted for patients colonized or at high risk for MRSA. For patients with a documented antibiotic allergy who did not receive cefazolin, the adherent regimen was defined as clindamycin or vancomycin with or without a gram-negative drug. The secondary outcome was the duration of antimicrobial prophylaxis.
There were 521,091 elective surgeries across 825 U.S. hospitals between 2019 and 2020. The mean age of patients was 65 years and 57% were female. Nine percent had a documented penicillin or non-sulfonamide allergy and 1.4% had documented MRSA carriage or were considered to be at high risk. Of the 521,091 surgeries, 308,760 (59%) were adherent to the ASHP guidelines. Hip replacement surgery had the highest rate of adherence (65%), while spinal procedures had the lowest (49%). The median hospital adherence rate was 64% (interquartile range [IQR], 40% to 80%). Hospitals in the Pacific region had the highest rate of adherence, while those in the West North Central and East South Central regions had the lowest. Notably, adherence significantly decreased from 2019 to 2020 (adjusted odds ratio [aOR] for 2020, 0.92; 95% confidence interval [CI], 0.91-0.94; P < 0.001).
Not surprisingly, cefazolin monotherapy was the most common regimen (56% of surgeries). Vancomycin was the antibiotic misused most frequently, which happened in 31% of all surgeries and accounted for 77% of nonadherent procedures. Vancomycin usually was added unnecessarily to cefazolin. The inappropriate use of gram-negative antibiotics occurred in 19% of nonadherent procedures. Furthermore, 65% of patients inappropriately received antimicrobial prophylaxis beyond day 1, with a median duration of two days (IQR, 1-2 days). Cefazolin was continued more often than vancomycin (64.3% vs. 16.5%, respectively).
The investigators performed a post-hoc analysis with patients who received cefazolin monotherapy vs. cefazolin and vancomycin. Most (91%) of the combination therapy recipients received a single day of vancomycin. After controlling for age, sex, comorbidities, procedure type, MRSA status, and receipt of other nephrotoxic agents, the use of cefazolin and vancomycin was associated with a 19% higher odds of developing acute kidney injury (AKI) compared to cefazolin alone (aOR, 1.19; 95% CI, 1.11-1.27; P < 0.001). This held true even for patients who received one day of vancomycin (aOR, 1.15; 95% CI, 1.07-1.23; P < 0.001).
Surgeons need to carefully balance the risks and benefits of perioperative antibiotic prescribing, which often can be nuanced and esoteric. Under the guise of preventing infections, it is easy to fall into the trap of using the wrong drug for the wrong duration. Therefore, it is not surprising Cabral and colleagues found that the antibiotic prophylaxis guidelines were not followed in nearly four out of every 10 common elective surgical procedures. Equally predictable was the inappropriate use of vancomycin, which increased the risk for AKI even when prescribed for a single day. Given that the ASHP guidelines were created based on evidence that maximizes surgical site infection prevention while minimizing the risk of adverse prophylaxis events, this nonadherence is both disappointing and very problematic. Surveys have shown that many surgeons are unaware of the guidelines, and hospitals have been slow to adopt them. Furthermore, this study also showed the detrimental effect of the COVID-19 pandemic on guideline compliance.
The study had some limitations worth considering. First, the retrospective design could have been affected by unmeasured confounding variables. Second, the ASHP guidelines are 10 years old and some recommendations might be out of date. Third, the 1.4% prevalence rate of MRSA in the cohort may have been an underestimate, thus limiting the generalizability of the findings to other settings where the prevalence of MRSA is greater.
Cabral and colleagues have provided compelling evidence of the need for clinicians and hospitals to do a better job using antibiotics for elective surgeries. A quality improvement initiative that raises awareness of the guidelines would be a good first step.