When it comes to preventing infections associated with orthopaedic procedures, the question of which antibiotic to use is only one of several concerns. How and where to administer antibiotics is another relevant question, not only in terms of infection-fighting effectiveness but also in terms of combatting the proliferation of antibiotic-resistant microbes.
In the September 19, 2018 issue of The Journal of Bone & Joint Surgery, Sweet et al. report on findings from a study in rats that compared the infection-prevention efficacy of intravenous (IV) cefazolin (n = 20) and IV vancomycin (n = 20) with local application of 4 antimicrobials—vancomycin powder (n = 20), cefazolin powder (n = 20), tobramycin powder (n = 20), and dilute Betadine lavage (n = 20).
The researchers induced infection by surgically implanting a polytetrafluoroethylene vascular graft near each rat’s thoracic spine and inoculating it with methicillin-sensitive Staphylococcus aureus (MSSA). After 7 days, all of the rats in each of the IV cefazolin, IV vancomycin, and Betadine lavage groups had grossly positive cultures for MSSA, “with bacterial colonies too numerous to count.” Ninety percent of the rats in the local cefazolin-powder group also had positive cultures, but the infection rates with vancomycin and tobramycin powder were much lower than those with the other four approaches (p <0.000001).
In addition to the main “disclaimer” about this study (namely, that its findings cannot be extrapolated to clinical practice in humans), the authors caution that “the effect of locally applied antibiotics on the emergence of resistant organisms is unknown,” while citing evidence that systemic administration of antibiotics is “associated with the emergence of resistant organisms at an alarming rate.”
Sweet et al. say they plan to follow up this study with a similar model to investigate the efficacy of local antimicrobials against the more problematic methicillin-resistant Staphylococcus aureus (MRSA)—and they suggest further that “clinical studies should be considered to determine the relative clinical efficacy of local versus systemic antibiotics for surgical infection prophylaxis in humans.”
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Andrew D. Duckworth, MSc, FRCSEd(Tr&Orth), PhD, in response to a recent study in JBJS.
Propionibacterium acnes (now called Cutibacterium acnes, according to an updated classification) is a ubiquitous microbe in the setting of shoulder surgery and is a well-established cause of indolent infection and prosthetic loosening1,2. In 2016, JBJS published a study by Hsu et al. investigating single-stage revision shoulder replacement in patients with subclinical infection, and the authors reported that almost half of the patients had >2 positive cultures for P. acnes3. However, the exact consequence of positive cultures at the time of primary surgery is unknown, and the efficacy of specific antibiotic prophylaxis against this microbe remains unclear.
In the June 6, 2018 issue of JBJS, Rao et al. randomised 56 patients scheduled to undergo a primary anatomic or reverse total shoulder replacement to receive either preoperative cefazolin alone (n=27) or a combination of cefazolin and doxycycline (n=29) 4. All patients had standard skin preparation at the time of surgery with both alcohol and chlorhexidine.
The primary outcome measure was ≥1positive culture after 14 days of incubation from either superficial and/or deep-tissue samples taken intraoperatively. The authors deemed that a decrease of 50% in the positive culture rate would be clinically significant. However, they found no significant difference between the groups in terms of the primary outcome measure (p=0.99). The authors carried out a secondary analysis to determine which other factors might be associated with ≥1 positive P. acnes culture and found that younger age, male sex, and a lower Charlson Comorbidity Index were predictive. Although this study was potentially underpowered, it demonstrated that in patients undergoing primary shoulder arthroplasty, preoperative doxycycline does not significantly reduce the prevalence of positive culture rates for P. acnes.
These findings are similar to those found in previous research and should lead us to question whether preoperative antibiotics aimed specifically at preventing P. acnes infection associated with shoulder arthroplasty are truly useful. P. acnes infections are difficult to detect both clinically and via culture—which makes any intervention difficult to measure, especially in a potentially underpowered study. Consequently, larger studies in this area would help to more definitively determine whether preoperative antibiotics aimed specifically at P. acnes decrease infection rates or, instead, may be adding to the growing problem of bacterial resistance. In particular, such trials seem most useful when they focus on patients who are at higher risk of these specific infections—in this case, younger, healthy males.
Finally, as Rao et al. wisely observed, doxycycline is a bacteriostatic agent, which slows the growth and production of bacteria, rather than a bactericidal agent, which kills bacteria. Given that antimicrobial limitation, doxycycline might not be the most appropriate prophylactic drug to be investigating for these cases.
Andrew D. Duckworth, MSc, FRCSEd(Tr&Orth), PhD is a consultant orthopaedic trauma surgeon at Edinburgh Orthopaedic Trauma, Royal Infirmary of Edinburgh, and he is a member of the JBJS Social Media Advisory Board.
- Gausden EB, Villa J, Warner SJ, Redko M, Pearle A, Miller A, Henry M, Lorich DG, Helfet DL, Wellman DS. Nonunion After Clavicle Osteosynthesis: High Incidence of Propionibacterium acnes. J Orthop Trauma. 2017 Apr;31(4):229-235.
- Chuang MJ, Jancosko JJ, Mendoza V, Nottage WM. The Incidence of Propionibacterium acnes in Shoulder Arthroscopy. 2015 Sep;31(9):1702-7.
- Hsu JE, Gorbaty JD, Whitney IJ, Matsen FA III. Single-Stage Revision Is Effective for Failed Shoulder Arthroplasty with Positive Cultures for Propionibacterium. J Bone Joint Surg 2016;98:2047-2051.
- Rao AJ, Chalmers PN, Cvetanovich GL, O’Brien MC, Newgren JM, Cole BJ, Verma NN, Nicholson GP, Romeo AA. Preoperative Doxycycline Does Not Reduce Propionibacterium acnes in Shoulder Arthroplasty. J Bone Joint Surg Am. 2018 Jun 6;100(11):958-964.