It’s time for orthopaedic surgeons to get involved in the battle against antimicrobial resistance

Antimicrobial resistance (AMR) is responsible for two million infections and 23,000 deaths annually in the United States alone. Globally, more than 700,000 people die each year of antibiotic-resistant infections. By the year 2050, AMR infections are predicted to be a larger killer than cancer and heart disease. The primary drivers for resistance are overuse and inappropriate use of antimicrobials. As much as half of all antibiotic use may be misuse. AMR is a global public health crisis by any measure.

Antimicrobial stewardship is a coordinated set of interventions designed to promote the appropriate use of antimicrobials. The goal is to improve patient outcomes, reduce microbial resistance, and decrease the spread of drug-resistant infections. Antimicrobial stewardship has been endorsed by the Centers for Disease Control and Prevention (CDC), Centers for Medicare & Medicaid Services, and The Joint Commission. In fact, the CDC recently issued an AMR challenge to AAOS to “commit to actions and results that combat resistance globally.” The message is clear: Orthopaedic surgeons must get involved in the battle against drug resistance.

Recent studies have shown a decrease in the efficacy of antibiotic prophylaxis before surgery. Combined with an increase in infection rates, that could have a marked impact on the risk-benefit calculus around and value derived from many elective orthopaedic reconstructive procedures.

Antimicrobial stewardship concepts

Two core strategies of antimicrobial stewardship are prior authorization and prospective audit/feedback. Prior authorization occurs when certain antibiotics must go through an approval process before they can be prescribed. Audits reduce nonoptimal antimicrobial therapy through direct feedback to the prescriber. Supplemental strategies include education, guidelines, clinical pathways, automatic substitutions, and intravenous-to-oral conversion protocols.

Antibiotic time-out

Antibiotic time-out is a new technique, recommended by the CDC and shown to improve the appropriateness of antibiotic prescribing. As with a surgical time-out, during an antibiotic time-out, the provider and team members purposefully review the patient’s antimicrobial therapy for appropriateness. The surgeon reviews each antibiotic order for indication and escalation or de-escalation opportunities, plans duration of therapy, and makes any necessary changes. This approach accommodates the need to initiate broad therapy during times of uncertain diagnosis, while encouraging transition to more targeted therapy as additional clinical information becomes available. Antibiotic time-outs can be performed informally or in a more documented manner, depending on provider and institution preferences.

Opportunities for the orthopaedic surgeon

Several antimicrobial stewardship issues are particularly relevant to orthopaedic surgeons. With so many opportunities to fight resistance and practice stewardship, where should orthopaedic surgeons begin?

One opportunity is to de-escalate empiric antimicrobial therapy appropriately when culture sensitivities demonstrate susceptibility to more narrow agents, such as with methicillin-susceptible Staphylococcus aureus (S. aureus) (MSSA). Vancomycin often is used empirically to treat surgical site infections (SSIs) and osteomyelitis, due to its activity against methicillin-resistant S. aureus (MRSA). However, when culture results demonstrate MSSA, vancomycin sometimes is continued inappropriately—when a narrower spectrum beta-lactam agent would be more appropriate. This practice can adversely affect patient outcomes because vancomycin has been shown to be inferior to beta-lactam agents as definitive therapy for certain MSSA infections. Studies have demonstrated higher recurrence rates, treatment failures, and even deaths. Because vancomycin is less efficacious than standard prophylaxis in a non-MRSA setting, its generic use for prophylaxis when concerns for MRSA are high might leave a patient relatively unprotected against some MSSA strains. Unless a patient has an allergy, orthopaedic surgeons should strive to utilize beta-lactam therapy for MSSA infections to maximize treatment efficacy and to minimize resistance development and adverse medication effects.

Another stewardship opportunity is to avoid overly broad antimicrobial coverage for skin and soft-tissue infections. Such infections are caused by a variety of microbes, including streptococci, MSSA, and MRSA. With the frequency of community-acquired strains of MRSA increasing, orthopaedic surgeons must identify patient risk factors in order to prescribe the most appropriate therapies and minimize the increased resistance and adverse effects associated with overly broad therapy. Adverse effects include Clostridium difficile infection (CDI) and increased nephrotoxicity associated with concomitant vancomycin and piperacillin/tazobactam.

Purulent soft tissue infections, including abscesses, warrant empiric MRSA coverage, as do severe nonpurulent infections, although such coverage should be de-escalated once culture results are available. Empiric MRSA coverage also is warranted if a patient demonstrates systemic signs of toxicity, prior MRSA infection or colonization, presence of MRSA risk factors, or proximity of a lesion to an indwelling medical device. Mild to moderate nonpurulent infections should be treated empirically with a beta-lactam agent or clindamycin.

A third very important and often forgotten opportunity to decrease resistance involves optimizing the duration and dosing of perioperative surgical prophylaxis. Significant controversy exists regarding the recommended duration of prophylaxis in routine orthopaedic cases. CDC guidelines released in 2017 recommend administration of preoperative antibiotics before skin incision. The guidelines also state that no further additional antibiotic doses need to be given after a surgical incision is closed in all clean and clean-contaminated procedures, including joint arthroplasties. In addition, many institutions use initial dosing that is weight dependent and use re-dosing for longer procedures.

Shorter postoperative prophylaxis is supported by data recently presented from a study that sought to characterize the relationship between duration of antibiotic prophylaxis and important outcomes. Using a large, multicenter national cohort of total joint, cardiac, vascular, and colorectal procedures, investigators found that increasing duration of postoperative antimicrobial prophylaxis was associated with higher odds of acute kidney injury and CDI. Additional days of routine antibiotic administration were not associated with reduced odds of SSI. AAOS disagrees with a shortened postoperative course and instead recommends that prophylaxis be continued for 24 hours postoperatively.

Unfortunately, sufficient data are not yet available regarding the optimal duration of antimicrobial prophylaxis. Several orthopaedic centers successfully follow the CDC recommendations of administering only single-dose prophylaxis (see “Meta-analysis Evaluates CDC’s Recommendation of a Single, Preoperative Dose of Antibiotics,” AAOS Now, October 2018). Those institutions are encouraged to review and publish data on infection rates to help elucidate the best course of action, because the risk of infection needs to be carefully balanced with the risks that additional antibiotic doses confer, including CDI, which can occur after a single dose. We must seek the answer to the optimal duration of prophylaxis to minimize infection risk while avoiding significant adverse reactions.

Conclusion

Orthopaedic surgeons must join the battle against antimicrobial resistance. Many stewardship opportunities exist. In particular, choosing the narrowest spectrum drug for the task at hand, conducting further research on drug duration requirements, decreasing drug duration when appropriate, and changing drugs once sensitivities are known will go a long way toward reducing AMR in the future.

Angie Fouts, PharmD, is a clinical pharmacist who leads the antimicrobial stewardship program at Mercy Medical Center – North Iowa in Mason City.

Patrick Maher, MD, is an orthopaedic surgery resident in the clinical scientist research track at the University of Pittsburgh Medical Center.

References:

1. Centers for Disease Control and Prevention: Antibiotic/Antimicrobial Resistance (AR/AMR). Available at: www.cdc.gov/drugresistance/index.html. Accessed September 18, 2018.
2. Dall C: CDC Chief: Antibiotic Resistance ‘Scary’ Threat to Modern Medicine. Available at: www.cidrap.umn.edu/news-perspective/2016/10/cdc-chief-antibiotic-resistance-scary-threat-modern-medicine. Accessed October 26, 2018.
3. Melton, CL: Are Antibiotic Stewardship Programs the Antidote to Antibiotic Overuse? Available at: www.infectiousdiseaseadvisor.com/antibiotics-antimicrobial-resistance/antibiotic-overuse-prevention-antibiotic-stewardship-programs/article/702830/. Accessed October 26, 2018.
4. Centers for Disease Control and Prevention: National Action Plan for Combating Antibiotic-Resistant Bacteria (2015). Available at: https://www.cdc.gov/drugresistance/pdf/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf. Accessed November 26, 2018.
5. Association for Professionals in Infection Control and Epidemiology: Antimicrobial Stewardship. Available at: https://apic.org/Professional-Practice/Practice-Resources/Antimicrobial-Stewardship. Accessed October 26, 2018.
6. Strymish JM, Brach-Elliman W, O’Brien, et al: Increasing duration of surgical prophylaxis increases antimicrobial-associated adverse events but does not decrease surgical site infections: an opportunity for stewardship. Presented at: IDWeek 2018; October 4, 2018; San Francisco, Calif.; Abstract 111. Available at: https://idsa.confex.com/idsa/2018/webprogram/Paper73284.html. Accessed November 26, 2018.
7. Branch-Elliman W, Ripollone JE, O’Brien WJ, et al: 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. PLoS Med 2017;14:e1002340.
8. Ryan, SP, Tan T, Seyler T: Meta-analysis evaluates CDC’s recommendation of a single, preoperative dose of antibiotics. AAOS Now October 2018.
9. Gandra S, Trett A, Alvarez-Uria G, et al: Is the efficacy of antibiotic prophylaxis for surgical procedures decreasing? Systematic review and meta-analysis of randomized control trials. Infect Control Hosp Epidemiol 2018:1-9.