Letter: Antibiotic Stewardship and Single-Dose Antibiotic Prophylaxis: A Word of Caution

To the Editor: Surgical site infections (SSIs) can range from superficial dehiscence to life-threatening conditions with significant clinical impact. Their management requires considerable expenses for health-care systems. SSIs are a primary module of the Patient Safety Component of the National Healthcare Safety Network (NHSN) reporting arm of the Centers for Disease Control and Prevention. There is a complimentary primary module for multidrug-resistant organism and Clostridium difficile infection (MDRO/CDI).1 Their aggregated institution-specific data is utilized by the Centers for Medicare and Medicaid Services (CMS) and state regulatory entities to monitor hospital safety and play a role in determining federal and state reimbursements. With respect to MDRO/CDI reporting, the NHSN has leveraged organizational guidelines to inform prevention efforts. Many institutions have created antibiotic stewardship programs to ensure that these guidelines are enforced. The “Clinical practice guidelines for antimicrobial prophylaxis in surgery” are joint guidelines developed by the American Society of Health System Pharmaceuticals, the Infectious Diseases Society of America, and the Society for Healthcare Epidemiology of America.2 In the section on “spine procedures with and without instrumentation”, a duration remark notes that “the majority of available studies of antimicrobial prophylaxis in spinal procedures have used single dose or regimens of <24 h duration.3 There is no high-quality evidence supporting a duration of >24 h,4 and some sources recommend only a single preoperative dose.”5,6 A closer examination of the body of evidence supporting this statement may lead to a different conclusion. Brown et al7 reviewed 5 single-dose vs no antibiotic studies in non-instrumented spine surgery published by a British antimicrobial working party that that found decreases in SSIs (for example, 12.7% vs 4.3%) that were not statistically significant. By their own admission, none of these studies powered appropriately (range n = 20-166) to detect a significant difference (n = 2000-5000 for appropriate power8,9).3 Dobzyniak et al4 was a retrospective review of 635 non-instrumented lumbar disc patients who received either a single-dose or multi-dose (3 or greater doses) regimen that found no significant difference in SSI (1.49% single-dose vs 1.15% multi-dose, P = .7). Hellbusch et al5 randomized N = 233 instrumented spine surgery patients to either receive single-dose vs 72-h intravenous antibiotics followed by 1 wk of oral antibiotic prophylaxis. They reported a reduction in SSIs from 4.3% to 1.7% that was not statistically significant and remarked “This study did not answer the question of whether the infection rate difference would have been significant with a larger number of patients”.5 Petignat et al6 conducted another randomized controlled trial of over 1200 herniated disc patients receiving non-instrumented spine surgery with or without single-dose antibiotic prophylaxis that reported a non-significant decrease in SSIs of 2.9% vs 1.3% (P = .07), but a significant decrease in spondylodiscitis infections (9 cases vs 0, P < .01). Data from prospective institutional databases substantiate that low SSI rates can be achieved with single-dose antibiotic prophylaxis for general neurosurgery, including spine cases.10 However, the supporting evidence for the joint guidelines affirm that the majority of studies are of single-dose antibiotic vs none regimens, many excluded instrumented spine procedures, and the studies were underpowered to detect a significant difference in SSI. A recent large, appropriately powered European study published in The Journal of Hospital Infection evaluated the efficacy of single-dose vs multi-dose antibiotic prophylaxis regimens in non-instrumented and instrumented spine surgery. Maciejczak et al11 conducted a prospective non-randomized cohort study of over 5000 patients over the course of a decade at a single institution examining a single-dose vs 72-h post-operative antibiotic prophylaxis protocols and found that in instrumented spine surgeries there was a significant decrease in SSI between single-dose (5.3%) and 72-h protocols (2.2%, P < .01). Multiple correspondence analysis of various SSI risk factors revealed that the 72-h antibiotic prophylaxis was the most important factor in minimizing SSI in their entire study cohort. While there are certainly flaws with a non-controlled, non-randomized pre/post-intervention study design, this remains the only appropriately powered study of single vs multi-dose antibiotic prophylaxis in both non-instrumented and instrumented spine surgery patients.11 On the recommendation of our hospital antibiotic stewardship committee (based on national guidelines mentioned above), our spine department switched from a multidose postoperative antibiotic prophylaxis to a single-dose protocol. The first 6 mo of this single-dose protocol yielded a greater than 2-fold increase in patients with SSIs that had to return to the operating room for surgical washout and wound revision compared to the 6 mo prior (0.73%-2.4%, P = .17). There were no clostridium difficile infections or concurrent increases in multi-drug resistant infections during this period. While this represents an underpowered observation that is not “high-quality supporting evidence”, it does represent a significant perioperative morbidity to a number of our patients. As more and more administrative oversight committees are devised within our institutions to meet national guidelines and quality reporting metrics (ie, decreasing MDRO/CDI), the imposition of broad-strokes clinical protocols need to be met with appropriate caution. As in this case, oftentimes these changes are based on over-interpretation of vague national guideline recommendations that are not specialty-specific. For departments dealing with a high proportion of complex spinal reconstruction procedures, individual adaptations of general guidelines might be required. Indeed, the most current North American Spine Society (NASS)12 guidelines endorse at least a single-dose antibiotic prophylaxis for uncomplicated simple (Grade B Recommendation) spine procedures and prolonged postoperative antibiotic regimens for more complex spine surgery including multilevel instrumented surgery (Grade C Recommendation). Thus, until there is conclusive, specialty-specific guidelines or Level 1 evidence to support protocols such as single-dose antibiotic prophylaxis regimens, institutional protocol adoption needs to be carefully monitored and scrutinized. In the interest of patient safety over patient safety metrics, we have reverted back to multi-dose antibiotic prophylaxis regimens follow spine surgery at our institution. In our opinion, this ongoing controversy justifies and calls for a sufficiently powered randomized controlled trial of single vs multi-dose antibiotic chemoprophylaxis regimen to reduce the incidence of SSI in multi-level instrumented spine surgery. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.