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Prophylactic antibiotics for joint arthroplasty: Which one and for howlong?
Timing and type of antibiotic used are important for many orthopedicprocedures.
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Infection following joint arthroplasty is a dreaded complication that is associated with immense social and economic cost. One of the most effective strategies to minimize periprosthetic joint infection (PJI) is the administration of perioperative antibiotics. The later was shown during the early days of joint replacement to be extremely effective in reducing the risk of PJI.
While efficacy and importance of prophylactic perioperative systemic antibiotics are not disputed, the dose, type, and the duration of antibiotic prophylaxis continue to be debated. The first published work on perioperative antibiotics by Burke and colleagues appeared in 1961 since then the questions of drug selection, perioperative or postoperative timing, dosing, and treatment duration have been continuously studied and adapted to the specifics of orthopedic surgery.
How they work
Antimicrobial prophylaxis acts as an adjunct at the operative site to decrease bacterial load in cases of contamination or tissue colonization. Contamination of the wound and colonization occurs during every orthopedic procedure.
The objective of the prophylaxis is to reduce the bacterial load especially when an implant is being used. The presence of an implant increases the risk of infection exponentially. Compared to 103-5 bacteria that are typically required to produce bone infection, the presence of a foreign body reduces that number to as few as 10 organisms.
Indications
The ideal prophylactic antibiotic should be specific to orthopedic infection while having no toxicity, good tissue penetration and a long half-life. Staphylococcus aureus is the predominant organism in orthopedic infections, with other mixed flora cultured in 10% to 11% of cases, streptococci in 9% to 10%, gram-negative bacilli in 3% to 6%, and enterococci in 3% to 7%, according to Burke and colleagues and Zimmerli and colleagues. First generation cephalosporins (such as cefazolin) are the best choices for prophylaxis as they fulfill the above mentioned criteria providing appropriate coverage with low toxicity and at minimum cost followed by other mixed flora cultured, streptococci, gram-negative bacilli and enterococci.
First generation cephalosporins such as cefazolin are the best choices for prophylaxis as they fulfill the above mentioned criteria and provide appropriate coverage with low toxicity and at minimum cost, according to Fonseca and colleagues and Brown and colleagues.
Second-generation cephalosporins such as cefuroxime have also been used as prophylactic agents because of their broader coverage which includes activity against gram negative bacteria. Marculescu and colleagues reported that they have less potency against typical staphylococci and their use in routine joint arthroplasty is limited.
Cephalosporins are safe drugs with reported hypersensitivity reactions being much lower than penicillins. Most allergic reactions are limited to urticaria or pruritus that may occur in 1% to 2% of patients. Other serious reactions such as bronchospasm, hypotension, and anaphylaxis may occur in 0.0001%. Cross-reactivity with penicillins is less than 10%, and less than 10% of patients reporting a penicillin allergy actually may show allergic response to cephalosporins. Penicillin skin testing is generally not predictive of a cephalosporin allergy. Nevertheless, patients with penicillin allergies have a threefold increased risk of hypersensitivity to unrelated drugs which includes cephalosporins.
There are some circumstances when the first-generation cephalosporins may not be appropriate choices for prophylaxis (See sidebar). One such case scenario is proven-and not suspected hypersensitivity to b-lactams antibiotics. Vancomycin or clindamycin may be used instead for prophylaxis in these patients. Vancomycin or clindamycin may be used instead in these patients. However, these antibiotics are less effective against staphylococci.
Vancomycin is the preferred drug for prophylaxis against methicillin resistant S aureus (MRSA). Hence, vancomycin should substitute first generation cephalosporins in patients with remote or recent history of MRSA infections. The latter includes institutionalized patients such as those staying at intensive care unit, regular visitors of hemodialysis units, or patients whose hospital stay extended beyond 5 days. It should also be used in patients who are a carrier of MRSA or have a remote or recent history with MRSA infections, as reported by Marculescu and colleagues.
Recent studies note the prevalence of MRSA in the community that is reaching around 30% in some regions, prompting a recommendation for the use of prophylactic vancomycin from the Hospital Infection Control Practices Advisory Committee. In contrast, the authors noted in 2001, Centers for Disease Control and Prevention (CDC) discouraged the prophylactic use of glycopeptides due to their selective use for MRSA and the fear in rise of vancomycin-resistant organisms.
In the absence of alternative antibiotics, newer drugs like teicoplanin have been successfully used in Europe but are not yet available in the United States, as reported by Zimmerli and Marculescu and colleagues. Daptomycin use for prophylaxis has been suggested, but data to support such application are not yet established.
Finally, patterns of bacterial resistance vary both geographically and temporally. All recommendations endorse the use of cephalosporins whenever possible with a unique regimen to be developed locally by each hospital based on the antibiotic susceptibilities reported by their microbiology laboratory.
Dosing
Burke and Zimmerli and colleagues report that a dose of 1 g to 2 g cefazolin is typically sufficient and Marculescu et al wrote that 1.5 g is the recommended dose for cefuroxime. Both antibiotics have excellent deep tissue penetration and a half-life of 1.5 to 2 hours, which is sufficient for most orthopedic procedures. Additional antibiotic doses are recommended in complicated cases that extend longer than the half-life of the drug or in cases with significant blood loss, according to Marculescu and Mangram and colleagues. Though cephalosporins can be administered over a short of period of time, slow infusion of vancomycin over 1 hour is recommended to prevent development of hypersensitivity reactions such as the red man syndrome. That hour is an important logistic issue that can disrupt the flow of operating rooms in elective cases.
Duration
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The original work by Burke and colleagues suggests that perioperative antibiotics should be given within 1 hour before surgery. The protective effect decreased significantly if the antibiotics were given 1 hour postoperatively. Classen and colleagues showed that the relative risk of surgical site infection increased by 2.4 times if antibiotics were given 3 hours after surgery and close to sixfold if they were given within the first 24 hours.
Administration of antibiotics at the time of anesthesia allows time for achieving microbicidal concentrations in tissues. Marculescu and colleagues suggested vancomycin should be administered within 2 hours presurgery due to the longer infusion time. To support such timing, Johnson and colleagues showed levels above the minimum inhibitory concentration (MIC) within 10 minutes of infusing 1.5 g of cefuroxime, with bone concentrations of antibiotics surpassing 60 times the MIC. Interestingly, the antibiotic level was minimally affected by use of a tourniquet.
Once administered, the exact duration of required antibiotic coverage is not known and a single dose is usually sufficient as long as the procedure time does not surpass two half-lives of the given drug.
Based on studies, the recommended duration of postoperative prophylaxis is 24 hours. Extending the prophylaxis beyond 24 hours has no significant effect on the incidence of infection and has been associated with an increased risk of resistance development.
Prolonged prophylaxis
The presence of an implant predisposes the host to delayed infection from hematogenous transfer, which is thought to be responsible for as many as 38% of knee implant infections. The hematogenous colonization can potentially stem from the transient bacteremia of minor surgeries or dental work. Nevertheless, an oral source is identified in less than 0.05% to 0.2% of infection cases, suggesting that dental work is rarely the cause.
Based on available evidence, the American Dental Association together with the American Academy of Orthopaedic Surgery has issued a statement recommending against prophylactic antibiotics before routine dental work. Simple efforts like chlorhexidine or antimicrobial mouthwashes can significantly decrease the rate of asymptomatic bacteremia and are preferred over systemic treatments.
Nevertheless, prophylactic antibiotics before dental procedures should be considered in patients with recent arthroplasty (within 2 years), previous periprosthetic infection, immunosuppressed states (diabetes, inflammatory arthritis, malignancy), and invasive dental work (extractions, implantation, root canal orthodontics). A single dose of amoxicillin or cephalexin provide appropriate coverage if given 1 hour before the procedure, and clindamycin has been used in penicillin allergic individuals. Antibiotic prophylaxis during dental or other surgical procedures for patients with a joint arthroplasty will continued to be studied and a more clear indication may develop with further investments in research.
A note from the editor
Look for the next installment of Infection Watch edited by Javad Parvizi, MD, FRCS, in the November issue.
Next month, Orthopedics Today will debut Emerging Technologies with Editor Anthony M. DiGioia III, MD.
For more information:
- Javad Parvizi, MD, FRCS, can be reached at the Rothman Institute, 925 Chestnut St., 5th Floor, Philadelphia, PA 19107. 267-339-3617; e-mail: parvj@aol.com. He receives research support from and is a consultant to Stryker, he receives miscellaneous funding from Johnson & Johnson and is a consultant to Smith & Nephew.
References:
- Brown AR, Vicca AF, Taylor GJ. A comparison of prophylactic antibiotic regimens against airborne orthopaedic wound contamination. J Hosp Infect. 2001;48(2):117-121.
- Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961;50:161-168.
- Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992;326(5):281-286.
- Fonseca SN, Kunzle SR, Junqueira MJ, Nascimento RT, de Andrade JI, Levin AS. Implementing 1-dose antibiotic prophylaxis for prevention of surgical site infection. Arch Surg. 2006;141(11):1109-1113; discussion, 1114.
- Mangram AJ. A brief overview of the 1999 CDC Guideline for the Prevention of Surgical Site Infection. Centers for Disease Control and Prevention. J Chemother. 2001;Spec No 1(1):35-39.
- Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999;20(4): 250-278.
- Marculescu CE, Osmon DR. Antibiotic prophylaxis in orthopedic prosthetic surgery. Infect Dis Clin North Am. 2005;19(4): 931-946.
- Rafiq I, Gambhir AK, Wroblewski BM, Kay PR. The microbiology of infected hip arthroplasty. Int Orthop. 2006;30(6):532-535.
- Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004;351(16):1645-1654.