Can We Improve Our Approach to Antibiotic Prophylaxis in Shoulder Arthroplasty?: Commentary on an article by Erick M. Marigi, MD, et al.: "Antibiotic Prophylaxis with Cefazolin Is Associated with Lower Shoulder Periprosthetic Joint Infection Rates Than Non-Cefazolin Alternatives".

Abstract

Commentary Periprosthetic joint infections (PJIs) following arthroplasties are relatively rare, occurring at rates of approximately 1% to 2% in both the upper and lower extremities1,2. However, these infections, when they do occur, wreak havoc on patient outcomes and are demoralizing to patients and surgeons alike. Several strategies are known to reduce the risk of surgical site infection in arthroplasties, including perioperative intravenous antibiotics3. In the lower extremity, the most common pathogens in PJIs are Staphylococcus aureus and Staphylococcus epidermidis, both gram-positive anaerobes that are sensitive to cephalosporin antibiotics, in particular, cefazolin. However, PJIs after shoulder arthroplasty are often characterized instead by Cutibacterium acnes, which is also gram-positive, but can be aerotolerant. C. acnes is also considered to be sensitive to cefazolin. Therefore, prophylactic coverage for shoulder arthroplasties is similar to those recommended for hip and knee arthroplasties: gram-positive coverage plus extended-spectrum gram-negative coverage, both provided by cephalosporin4. However, challenges arise when patients cannot take cephalosporin due to reasons including penicillin and cephalosporin allergies. The second-line antibiotic choices in these cases are typically clindamycin or vancomycin, both of which provide coverage that is similar, but not a perfect match, to cephalosporin. In both lower-extremity and upper-extremity arthroplasties, studies have found that second-line antibiotics are not as effective in preventing PJIs5,6. However, the available evidence is observational in nature, which can be confounded by patient and surgeon factors. Prospective randomized studies have yet to confirm these findings. In their study, Marigi et al. report on a large number of patients who underwent shoulder arthroplasty and had registry data. The overall PJI rate was 1.3%, with the most common causative organism reported to be C. acnes. The authors found that the administration of prophylactic intravenous antibiotics other than cefazolin (clindamycin, vancomycin, and other) was an independent risk factor for PJI, with >2-fold increase in the rate of infection. This finding was even more pronounced with the diagnosis of a C. acnes infection. Despite the risk of unknown confounding variables in this observational study, the data represent higher-level evidence than in previously published studies and corroborate the conclusion that cefazolin provides the best prophylactic coverage in shoulder arthroplasty. There is a growing body of evidence that there is extremely low cross-reactivity between penicillin and later-generation cephalosporins7. Many surgeons believe that it is safe to administer cefazolin even in patients with penicillin allergies, as long as there is no documented history of angioedema or anaphylaxis. The recently published Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial that randomized 604 patients undergoing lower-extremity oncologic endoprosthetic reconstruction to 1 or 5 days of postoperative prophylactic intravenous cephalosporin did not exclude patients with penicillin allergies unless there was a history of anaphylaxis or angioedema8. There were no documented serious unexpected adverse reactions reported, despite the fact that patients with penicillin allergies were included on the basis of surgeon comfort with the protocol. Marigi et al. suggest that all patients with penicillin allergies be tested preoperatively or be given a test dose of cefazolin intraoperatively to monitor for an adverse reaction. This is a very reasonable suggestion, as it could benefit both surgical patients and the health-care system by avoiding PJIs that occur due to insufficient antimicrobial prophylactic coverage. In addition, patients with a remote history of a penicillin allergy, most likely related to historical drug preparations, or a history of a rash due to penicillin, could be automatically considered candidates for intravenous cefazolin9. All attempts should be made to provide the best infection prophylaxis, according to the available evidence, in patients undergoing shoulder arthroplasty. At this time, the available evidence points to cephalosporin. Given the consistent findings of the superior efficacy of cephalosporin in the published literature, albeit through observational data, it may be challenging to design a randomized study that would be considered acceptable and ethical to orthopaedic surgeons. For now, the study by Marigi et al. provides some of the strongest evidence to date for the use of intravenous cephalosporin in PJI prophylaxis in shoulder arthroplasty.