Are Your Antibiotic Prescriptions In Line With Evidence-Based Medicine?

Author(s): 
By Ann C. Anderson, DPM, and John S. Steinberg, DPM

   Many of the treatment decisions made on a daily basis in medicine are not founded on or confirmed by the best available science. Some of these decisions are based on historic clinical standards and teachings yet to be scientifically proven while other decisions are made out of habit or sometimes a lack of appropriate information.    The questions raised in this discussion are not intended to imply that every treatment decision must be based on randomized controlled trials. However, we do hope to point out many clinical misconceptions regarding the prescribing and usage of antibiotics.    This article will raise some very controversial points about the practice of antibiotic prescriptions. We are not seeking to establish a new standard of care or question the way one practices. We are simply facilitating discussion regarding the evidence-based practice of medicine and how it might relate to the antibiotic prescriptions we write on a daily basis.

Why DPMs Overprescribe Antibiotics

   In close similarity to the entire medical profession, podiatrists are often guilty of overprescribing antibiotics. There are certainly many reasons for this practice, not the least of which is a fear of being found negligent in a potential legal action. When faced with a dilemma of whether or not to prescribe, the physician will likely decide that he or she can minimize the risk of potential legal action by including an antibiotic prescription in the treatment plan.    While clinicians should not withhold antibiotics if there is reasonable concern for an infection, they should not generally give antibiotics as part of a shotgun approach to an unknown problem. Performing a thorough patient examination and evaluation should enable one to determine whether there is an infection and pursue an appropriate course of treatment.    Patient expectation is another key factor that drives unnecessary antibiotic prescriptions. Just as patients go to their primary care doctor for antibiotics when they have a simple cold virus, patients expect to visit their podiatrists and receive prescription medication to cure their ailments. Many patients do not feel they have received proper attention until they get a prescription from their doctor. Additionally, patients with wounds often do not understand the difference between a chronic wound contamination and an acute wound infection. At the most, one would treat chronic wound contamination with simple topical management whereas an acute wound infection would require oral or parenteral antibiotic management.    As with many medical decisions, proper documentation is essential. When clinicians decide an antibiotic is not medically necessary, they should document that decision and provide an explanation. Conversely, when one decides to prescribe an antibiotic, he or she should discuss the clinical findings of infection in the treatment note for that date in order to justify the risk/benefit ratio of the decision.    Additionally, the local standard of care often drives antibiotic prescriptions. No physician wants to be cited as deviating from the standard of care and therefore is easily swayed by the prescribing habits of the local podiatric community. This overprescribing can lead to the proliferation of resistant organisms and can contribute to gastrointestinal complications and secondary infections from the altered homeostasis, which can result from unnecessary antibiotic prescribing.

When Are Prophylactic Antibiotics Appropriate?

   In addition to the over-prescribing of antibiotics, excessive use of prophylactic antibiotics for surgery is also an issue. Antibiotic prophylaxis accounts for approximately 30 percent of all antibiotics administered on surgical services in the United States.1 Prophylaxis is defined as the use of antibiotics to prevent infection. The objectives of prophylactic antibiotic use include preventing naturally occurring organisms from proliferating in a sterile surgical site, preventing organisms from producing disease and preventing infection by exogenous organisms.1 There are numerous advantages of using prophylactic antibiotics. These advantages include preventing potential infection in high-risk surgical procedures, protecting immunocompromised patients and preventing foreign implant colonization.    However, Williams and Gustillo noted the possible risks of indiscriminate use of preventive antibiotics for orthopedic surgery. These risks included unnecessary expense, drug-related side effects and the potential to influence local and hospital microflora.2 The main concern with the indiscriminate use of prophylactic antibiotics is the emergence of resistant bacteria, including postoperative MRSA infections from clean surgical procedures.    Considering that the incidence of infection in clean orthopedic surgery without antibiotic prophylaxis is 0.5 percent to 6.5 percent, it is unrealistic to think that prophylaxis is necessary in every case. Joseph, et. al., and Leaper agree that clean surgical procedures without the implantation of a prosthesis in patients with normal defenses do not necessarily justify routine use of prophylactic antibiotics.3,4    When are prophylactic antibiotics indicated? According to Joseph and Kosinski, antibiotic prophylaxis is indicated for foreign device implantation, trauma surgery, prolonged operative time and immunocompromised patients.3 Researchers have shown that implantating any foreign body impairs wound healing as well as the local immune response and defense mechanisms.5 Most of the literature in this area is based upon total hip and total knee prosthetic implants and is extrapolated to apply to the use of metal hardware implants in podiatric surgery. Based on the orthopedic literature, Joseph and Kosinski state that although the risk of developing an infection of a prosthetic implant is low, infection is catastrophic when it does occur. Therefore, they recommend using prophylactic antibiotics when performing clean, elective surgical procedures with an implant.3    In most traumatic injuries, the high occurrence of infection accounts for the primary cause of many complications including non-unions and instability following the injury.6 In trauma cases, researchers have shown that one should give antibiotics within three to six hours after inoculation in order to reduce the incidence of infection. Studies have shown a lower rate of postoperative osteomyelitis and infection when surgeons have used prophylactic antibiotics in trauma patients. Therefore, prophylactic antibiotics are considered an essential part of traumatic injury management.3    Patients undergoing surgical procedures with a prolonged operative time are at increased risk for infection. Since most intraoperative contamination can be traced to airborne organisms from the patient or operating room personnel, Joseph and Kosinski recommend prophylaxis for surgical procedures lasting more than two to three hours.3 Bowler, et. al., recommend restricting acute wound prophylaxis to a single dose of antibiotics at the beginning of the operation with an additional dose if operative time exceeds three to four hours. The objective is to achieve a high concentration of antibiotics at the time of incision and throughout the surgical procedure.8    Joseph and Kosinski state that one should consider antibiotic prophylaxis for immunocompromised patients, including patients with diabetes and the elderly.3 A conflicting view is presented by Zgonis, et. al., in their retrospective study of 555 patients. In this study, 55 percent of the patients received prophylactic antibiotics while 45 percent were not given any antibiotics.9 The antibiotic group had a 1.6 percent wound infection rate versus 1.4 percent for the group not given antibiotics. They noted the group that received antibiotics had more complex and longer surgical procedures, and there was more frequent use of internal and external fixation devices.    In the study, researchers found that none of the examined factors, including age, gender, type of surgical procedure, operative time, tourniquet use, past medical history or use of internal fixation, were predictive of post-op wound infection or complication.9 Based upon these results, one could conclude that preoperative antibiotics are not indicated in clean podiatric surgical procedures.    Cierny and Mader recommend antibiotic prophylaxis based upon the standard classification of surgical wounds.1 This classification system takes into account the surgical approach, immune system of the patient and risk of a postoperative infection. Clean wounds include elective surgery on non-compromised hosts under ideal operating room conditions. Since the overall incidence of wound infection is less than 5 percent, Cierny and Mader state that no antibiotic prophylaxis is indicated.1    Clean/contaminated wounds involve entering the oropharyngeal cavity, and the lumens of the respiratory, alimentary or genitourinary tracts. This category also includes clean surgery performed on immunocompromised hosts or surgery involving a break in sterile technique. Wound infections occur in approximately 10 percent of these procedures. Therefore, surgical prophylaxis is recommended for this category.1    Contaminated/dirty wounds include surgery performed through traumatic wounds, a major break in sterile technique and operating at the site of active infection. These procedures have infection rates ranging from 20 to 40 percent, necessitating the need for antibiotic prophylaxis and/or therapy.1

Finding The Appropriate Antibiotic And Duration Of Therapy For Prophylaxis

   When deciding to prescribe a preoperative antibiotic for prophylaxis, it is important to determine which antibiotic is appropriate for that particular scenario. A prophylactic agent should be non-toxic, inexpensive, have a prolonged serum/tissue half-life, not foster resistance and be active against the most common organisms.3    Williams and Gustillo favor cephalosporins as the sole prophylactic agent because they are relatively non-toxic, inexpensive and effective against most potential pathogens in orthopedic surgery.2 For clean, elective orthopedic procedures, they recommend 2 grams of cefazolin IV prior to surgery and 1 gram IV every eight hours for 24 hours after surgery.2    Studies based on hip replacement procedures recommend giving prophylactic antibiotic postoperatively for 24 hours and then discontinuing the medication.2 There is no evidence to support continuing prophylactic antibiotics for more than 24 hours after surgery. Recent studies on total hip arthroplasty indicate there is no difference in infection rates found between patients receiving one day of preventative antibiotics and those receiving antibiotics for seven to 10 days after surgery. Therefore, the studies conclude it is not worth the added cost or risk to the patient to continue antibiotics for more than 24 hours.2

What You Should Know About Antibiotic Management Of Hospitalized Patients

   The most common reason for in-patient antibiotic therapy orders in podiatry is when a patient is admitted for an acute infection. This scenario generally calls for initial empiric antibiotic therapy to cover for a broad spectrum of organisms with the anticipation that the culture and sensitivity results will allow for a selection of a more narrow spectrum antibiotic regimen.    Bowler, et. al., recommended starting empiric therapy with a broad spectrum antibiotic as soon as possible for acute infections and subsequently obtaining cultures in order to identify clinically significant isolates from wound cultures.    The microbiology data will provide guidance as to the most appropriate antibiotic therapy.8 For chronic wounds, in which culture isolates reveal polymicrobial aerobic and anaerobic infections, broad spectrum antibiotics are indicated if the wound shows evidence of clinical infection. Single agent, broad spectrum antibiotics include cefoxitin, imipenem and ticarcillin-clavulanate. One can add metronidazole or clindamycin for anaerobic bacterial coverage.1    Antibiotic management can often grow complex with patients who have endured multiple hospital admissions and have polymicrobial infections of bone and soft tissue. It is important to maintain records of prior antibiotic orders, treatments and culture results as this information can play a vital role in helping to delineate a new course of therapy for patients on chronic or repeat antibiotics. Cierny and Mader point out the difficulty in treating patients with prolonged periods of hospitalization due to the likelihood that they will become colonized with difficult-to-treat organisms and will likely require treatment with multiple antibiotics.1

What The Literature Reveals About Topical Antimicrobial Agents

   There are numerous topical antimicrobial products available for treating incisions and wounds. These products can be divided into two broad categories: topical antibiotics and topical antiseptics. The general goal of topical antimicrobial therapy is to control the local microbial load and flora of the wounds.    While the newer silver-containing antimicrobials seem to minimize this effect, many topical treatments are cytotoxic to the underlying wound bed. Accordingly, one should limit the use of these topical treatments to wounds in which contamination and colonization are believed to be impairing the wound progress. Once one has reestablished the wound homeostasis, the practitioner should consider changing therapy in order to avoid cytotoxicity. While relying on topical antimicrobials as mono-therapy for a problematic infected wound is rarely indicated, topical agents can often make a great complement to wound cleansing/debridement and reduce microbial load.    In the absence of advancing cellulitis, bacteremia and fever, Bowler, et. al., state that topical antimicrobial agents may offer the most useful treatment.8 Applying topical antibiotics to a non-healing wound can provide a high concentration of a drug at the local site while avoiding the systemic allergic reactions and more widespread effects of parenteral antibiotics. Limitations of topical treatments include patient compliance, small depth of penetration and potential for a local contact dermatitis.    Widely used topical antibiotics include mupirocin, bacitracin, neomycin, polymyxin B and gentamycin. These agents are effective against a wide range of organisms including gram-positive and gram-negative bacteria. They are used to treat superficial open wounds. Researchers have shown that ointments containing bacitracin, polysporin and neomycin decrease bacterial colonization and increase reepithelialization rates of open wounds.1 One key precaution when using “triple antibiotic” ointments is the relatively high prevalence of anaphylactic allergic contact dermatitis to the neomycin component of the ointment. For this reason, we recommend using bacitracin zinc ointment in place of the triple antibiotic ointment.    Clinicians may employ topical antiseptics such as dilute sodium hypochlorite, acetic acid and iodine to decrease the risk of infection in intact skin or minor wounds.11 One may use various combinations as preoperative disinfectants of the skin. Additionally, clinicians can use dilute sodium hypochlorite and acetic acid for short course therapy in open wounds in need of decontamination from surface bacterial load.    Most antiseptics, including iodine and chlorhexidine, are not indicated for long-term use in open wounds because they impede wound healing by direct cytotoxic effects to keratinocytes and fibroblasts.11 Iodine has been shown in vitro to impair cell function involved in normal wound healing.12 Although the prophylactic role of iodine in acute surgical wounds is widely supported in the literature, there is minimal evidence to support its use in chronic wound prophylaxis.13    Silver products offer an additional category of topical agents that are effective at controlling the local microbial load in open wounds. These include silver nitrate, silvadene and the more recently developed nanocrystalline silver-controlled release systems. Researchers have shown that silver products reduce the number of viable bacteria in a contaminated wound.14 Silver is toxic to microbes as it poisons the respiratory enzymes and components of the electron transport chain, and impairs DNA functions of microbes. Silver products exert their bactericidal properties by reacting with thiol groups, rendering bacterial proteins inactive by inhibiting DNA replication.11    To maintain its microbicidal activity, silver must be continuously available in its free ionic form within an aqueous environment in order to interact with bacteria. Due to the fact that silver ions react rapidly with chloride ions in body fluid, silver-containing topical creams and solutions require multiple daily applications with dressing changes.8 Therefore, controlled, sustained release silver sheet products, such as Acticoat, Actisorb and Aquacel Ag, are favored for chronic wound care. Typically with these products, when the silver ions are hydrated, they will begin the slow and continuous release of ions that will be maintained until the next dressing change.    Jones, et. al., noted that silver-based products are beneficial for their broad-spectrum activity and low propensity to induce bacterial resistance.15 Silver products have an additional benefit in that they are effective in killing antibiotic-resistant strains of bacteria. Researchers have shown that silver-coated dressings reduce the level of viable organisms in 30 minutes to non-detectable levels, rapidly eliminating organisms that are inhibiting the wound healing process.15 They have also shown that silver sheet dressings sustain antimicrobial activity for 14 days in vitro.15 When in direct contact with the microorganism, topical silver products can rapidly kill commonly encountered wound pathogens including antibiotic-resistant bacteria (MRSA, VRE), anaerobic bacteria and even yeast.15 Although extremely rare, topical silver dressings can contribute to complications such as neutropenia, erythema multiforme, crystalluria and methemoglobinuria.11

Pertinent Pointers On Antibiotic Beads

   An additional mode of topical antibiotic delivery is the absorbable or non-absorbable antibiotic bead. Surgeons can prepare these beads and use them to provide a temporary high local concentration of antibiotics in patients with chronic osteomyelitis or complicated wounds with space defects. Surgeons usually use antibiotic beads in conjunction with systemic antibiotics to improve the local antibiotic concentration to the area of concern. The non-absorbable beads are composed of PMMA, a powdered bone cement polymer that serves as the carrier for the antibiotics. One can mix the PMMA with a selected antibiotic, usually gentamycin, tobramycin or vancomycin.    After mixing the PMMA with antibiotics, surgeons usually form the beads onto a stainless steel wire and apply them to the wound. The antibiotic elution from the beads follows a biphasic distribution. The bulk of the local antibiotic release occurs in the first hours to days after implantation and the remaining elution can persist for years.16 Perry, et. al., also noted that the rate of diffusion of antimicrobial agents from the PMMA beads is directly related to the size of beads and the antimicrobial concentration.17    Chen, et. al., have performed animal studies on rabbits with osteomyelitis and noted that implanting tobramycin beads in infected wounds enhances the clearance of bacteria from contaminated, dead bone.18 They recommend the use of antibiotic beads in conjunction with systemic antibiotics to treat osteomyelitis. They also noted that the reduction in bacterial count due to the tobramycin beads was independent of the activity of systemic antibiotics and when they are used in conjunction with systemic antibiotics, they have an additive effect in reducing the bacterial count.    This evidence solidifies the role of antibiotic beads as an adjunctive therapy to systemic antibiotics in treating infected bone and soft tissue. Newer calcium sulfate bone products allow the formation of antibiotics into beads or pellets that will resorb over four to six weeks in the body and therefore obviate the need for a separate procedure to remove the beads.

Final Notes

   While we as podiatric physicians can successfully manage the clear majority of foot infections requiring antibiotics, it is important to know when to ask for help. There are a few challenging circumstances when it is advisable to consult with infectious disease specialists in order to coordinate a proper antibiotic regimen. Patients with non-healing wounds, chronic renal insufficiency/failure and patients who culture persistent resistant organisms pose a challenge to all healthcare professionals and are best treated with a coordinated team approach.    Resistant organisms pose a rather unique set of circumstances in which stronger antibiotics and antibiotic combinations are necessary to eradicate infection. The specialty of infectious disease management was developed to facilitate an appropriate treatment course for these complex patients and to utilize the best possible evidence-based science in safely treating a problematic infection. Serious medical consequences can result from mismanagement of a complex infection and can not only cost the patient his or her limb, but also place the patient in jeopardy for hearing loss and renal failure. Often, one must adjust the dose of the antibiotics throughout the treatment course in order to monitor peak and trough levels, and ensure the patient receives the proper therapeutic dosage. Dr. Anderson is a third-year resident at the INOVA Fairfax Hospital Podiatric Residency Program in Fairfax, Va. Dr. Steinberg is an Assistant Professor in the Department of Surgery at Georgetown University in Washington, D.C. He is also a Fellow of the American College of Foot and Ankle Surgeons. References 1. Mader JT, Cierny GC. The Principles of the Use of Preventive Antibiotics. Clinical Orthopedics and Related Research 190, 75-82, 1984. 2. Williams DN, Gustillo RB. The Use of Preventive Antibiotics in Orthopedic Surgery. Clinical Orthopedics and Related Research 190, 83-88, 1984. 3. Joseph WS, Kosinski MA. Prophylaxis in Lower Extremity Infectious Diseases. Clinics in Podiatric Medicine and Surgery 13(4): 647-660, 1996. 4. Leaper DJ. Prophylactic and Therapeutic Role of Antibiotics in Wound Care. American Journal of Surgery 167(1A): 15S-20S, 1994. 5. Dougherty S. Pathobiology of infection in prosthetic devices. Rev Infect Dis 10: 1102-1117, 1988. 6. Antrum R, Solomkin J. A review of antibiotic prophylaxis for open fractures. Orthop Rev 16:246-254, 1987. 7. Burke JK. The effective period of preventing antibiotic action in experimental incisions and dermal lesions. Surgery 50:161-8, 1961. 8. Bowler PG, Duerden BI, Armstrong DG. Wound Microbiology and Associated Approaches to Wound Management. Clinical Microbiology Reviews 14 (2): 24-269, 2001. 9. Zgonis T, Jolly GP, Garbalosa JC. The Efficacy of Prophylactic Intravenous Antibiotics in Elective Foot and Ankle Surgery. Journal of Foot and Ankle Surgery 43(2): 97-103, 2004. 10. Goldstein EJC. Selected nonsurgical anaerobic infections:therapeutic choices and the effective armamentarium. Clin Infect Dis 18: S273-279, 1994. 11. Lio PA, Kaye ET. Topical Antibacterial Agents. Infect Dis Clin N Am 18:717-733, 2004. 12. Burks RI. Povidone-Iodine solution in wound treatment. Phys Ther 78: 212-218, 1998. 13. Gilchrist B. Should Iodine be reconsidered in wound management? J Wound Care 6:148-150. 14. Wright JB, Lam K, Burrell R. Wound Management in an Era of Increasing Bacterial Antibiotic Resistance: A Role for Topical Silver Treatment. Am J Infect Control 26(6): 572-577, 1998. 15. Jones SA, Bowler PG, Walker M, Parsons D. Controlling Wound Bioburden with a Novel Silver-Containing Hydrofiber Dressing. Wound Repair and Regeneration 12(3): 288-294, 2004. 16. Wininger DA, Fass RJ. Antibiotic Impregnated Cement Beads for Orthopedic Infections. Antimicrobial Agents Chemother 40 (12): 2675 - 2679, 1996. 17. Perry AC, Rouse MS, Khaliq Y, Piper KE, Hanssen AD, Osmon DR, Steckelberg JM, Patel R. Antimicrobial Release Kinetics From Polymethylmethacrylate in a Novel Continuous Flow Chamber. Clinical Orthopedics and Related Research 403: 49-53, 2002. 18. Chen NT, Hong H, Hooper DC, May JW. The Effect of Systemic Antibiotic and Antibiotic-Impregnated Polymethylmethacrylate Beads on the Bacterial Clearance in Wounds Containing Contaminated Dead Bone. Plastic and Reconstructive Surgery 92(7): 1305-1311, 1993. Additional References 19. Court-Brown CM. Antibiotic Prophylaxis in Orthopedic Surgery. Scand J Infect Dis Suppl. 70:74-79, 1990. 20. Nordeen CW. Antibiotic Prophylaxis in Orthopedic Surgery. RID 13 (Suppl 10): 842-846, 1991. Editor’s Note: For related articles, see the April 2004 supplement, “Treating MRSA Infections,” the article, “When Or When Not To Use Preoperative Antibiotics” in the September 2000 issue or check out the archives at www.podiatrytoday.com.
 

 

References:

CE Exam #130 Choose the single best response to each question listed below. 1. Antibiotic prophylaxis accounts for approximately __ percent of all antibiotics administered on surgical services in the United States. a) 5 percent b) 10 percent c) 25 percent d) 30 percent 2. When do Joseph and Kosinski recommend using antibiotic prophylaxis? a) When performing clean, elective surgical procedures with an implant b) When performing short surgeries c) Only in surgeries for non-traumatic injuries d) None of the above 3. There is no evidence to support continuing prophylactic antibiotics for more than __ hours after surgery. a) 12 b) 48 c) 24 d) 6 4. In trauma cases, how long after inoculation should one give antibiotics to reduce the chance of infection? a) Two to four hours b) Three to six hours c) Four to eight hours d) Six to 12 hours 5. What is the main concern with indiscriminate use of prophylactic antibiotics? a) Drug-related side effects b) The emergence of resistant bacteria c) Infection from implants d) Expense 6. What should one use instead of a “triple antibiotic”? a) Neomycin b) Cefazolin c) Polymyxin B d) Bacitracin zinc ointment 7. How long will silver sheet dressings sustain antimicrobial activity in vitro? a) Seven days b) 10 days c) 14 days d) None of the above 8. The study by Chen et. al., concluded that implanting ____ beads in infected wounds enhances the clearance of bacteria from contaminated, dead bone. a) Tobramycin b) Vancomycin c) Clindamycin d) Gentamycin 9. A prophylactic antibiotic agent should be … a) Non-toxic b) Have a prolonged serum/tissue half-life c) Active against the most common organisms d) All of the above 10. Which of the following statements is true about surgical procedures for prosthetic implants? a) Infection is catastrophic when it occurs. b) The risk of developing an infection is low. c) If an infection does occur, it is relatively minor. d) A and B Instructions for Submitting Exams Fill out the enclosed card that appears on the following page or fax the form to NACCME at (610) 560-0502. Within 60 days, you will be advised that you have passed or failed the exam. A score of 70 percent or above will comprise a passing grade. A certificate will be awarded to participants who successfully complete the exam. Responses will be accepted up to 12 months from the publication date.

 

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