Vancomycin prophylaxis in prosthetic joint surgery?
2019; Elsevier BV; Volume: 26; Issue: 1 Linguagem: Inglês
10.1016/j.cmi.2019.10.007
ISSN1469-0691
Autores Tópico(s)Antimicrobial Resistance in Staphylococcus
ResumoThe efficacy of preoperative surgical antibiotic prophylaxis in preventing surgical site infection has been established [1Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar, 2AlBuhairn B. Hind D. Hutchinson A. Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review.J Bone Jt Surg Ser B. 2008; 90: 915-919Crossref PubMed Scopus (188) Google Scholar, 3Uçkay I. Hoffmeyer P. Lew D. Pittet D. Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update.J Hosp Infect. 2013; 84: 5-12Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar]. The choice of antibiotic to use for this purpose is determined largely by the expected microorganism at the surgical site that is often responsible for surgical site infection (SSI), i.e. Staphylococcus aureus [1Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar, 2AlBuhairn B. Hind D. Hutchinson A. Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review.J Bone Jt Surg Ser B. 2008; 90: 915-919Crossref PubMed Scopus (188) Google Scholar, 3Uçkay I. Hoffmeyer P. Lew D. Pittet D. Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update.J Hosp Infect. 2013; 84: 5-12Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar]. In many countries, cefazolin, an antibiotic belonging to the first generation of cephalosporins, is often used. It is also often used in prosthetic joint surgery [[1]Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar,[2]AlBuhairn B. Hind D. Hutchinson A. Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review.J Bone Jt Surg Ser B. 2008; 90: 915-919Crossref PubMed Scopus (188) Google Scholar]. However, prosthetic joint surgery has some key differences from other types of surgery. In prosthetic joint surgery, antibiotic prophylaxis is also used because it is thought to be able to prevent the newly implanted prosthetic from being colonized by bacteria that can lead into prosthetic joint infection (PJI). Biomaterial in the human body, and the lesion caused by its implantation, are known to increase the susceptibility to infection [[4]Elek S.D. Conen P.E. The virulence of Staphylococcus pyogenes for man; a study of the problems of wound infection.Br J Exp Pathol. 1957; 38: 573-586PubMed Google Scholar]. The other important difference is that bacteria which cause PJI are not only virulent bacteria such as S. aureus but also ubiquitous members of the microbiome of human skin, such as coagulase-negative staphylococci, Cutibacterium acnes, and other skin commensals [[3]Uçkay I. Hoffmeyer P. Lew D. Pittet D. Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update.J Hosp Infect. 2013; 84: 5-12Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar]. These bacteria are known to cause delayed PJI, that is, PJI acquired during implantation but with symptoms occurring between 3 weeks and 2 years after implantation. Delayed PJI is often more difficult to diagnose than early PJI (acquired during implantation with symptoms occurring within 3 weeks of prosthetic implantation) where pain may be the only symptom [[1]Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar]. Since the duration of the symptom in this type of PJI is rather long, implant retention is usually impossible and the treatment with the highest chance of success is the removal of the implant followed by the implantation a new prosthesis [[5]Zimmerli W. Trampuz A. Ochsner P.E. Current concepts: prosthetic-joint infections.New Engl J Med. 2004; 351: 1645-1654Crossref PubMed Scopus (673) Google Scholar]. The clinical and economic impact for patients with PJI caused by these low-virulence bacteria is arguably higher than for patients with acute PJI due to virulent bacteria such as S. aureus, where debridement, implant retention and the use of antibiotics is the treatment of choice. Unfortunately, in many parts of the world around 80% of Staphylococcus epidermidis strains isolated from hospitalized patients are resistant to methicillin and thus also to cefazolin, as shown in a surveillance study on bloodstream infection in Belgian hospitals [[6]Deplano A. Vandendriessche S. Nonhoff C. Dodémont M. Roisin S. Denis O. National surveillance of Staphylococcus epidermidis recovered from bloodstream infections in Belgian hospitals.J Antimicrob Chemother. 2016; 71: 1815-1819Crossref PubMed Scopus (20) Google Scholar] and in National Nosocomial Infections Surveillance in the United States [[7]System N.N.I.S. National nosocomial infections surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004.Am J Infect Control. 2004; 32: 470-485Abstract Full Text Full Text PDF PubMed Scopus (2513) Google Scholar]. In our university hospital we have reproduced this number. We found that 5467 out of 6738 (81%) of all S. epidermidis isolates from blood culture in the period between January 2014 and July 2019 were methicillin-resistant. Since many patients who receive prosthetic joints do not have previous hospital admissions, their S. epidermidis might be considered as community-acquired. We estimated the number of community-acquired S. epidermidis strains by including S. epidermidis from blood cultures of newly admitted patients only, and we found that 218 of 587 isolates (37%) from unique patients were methicillin-resistant. We can make a rough estimation on the number of PJIs that may be preventable when appropriate prophylaxis for S. epidermidis is given by using the PJI prevalence of 1% (low estimate), and that one third of new prosthetic joints infections will be of delayed type due to coagulase-negative staphylococci [[8]Fernández-Sampedro M. Fariñas-Alvarez C. Garces-Zarzalejo C. Alonso-Aguirre M.A. Salas-Venero C. Martínez-Martínez L. et al.Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection.BMC Infect Dis. 2017; 17: 592Crossref PubMed Scopus (40) Google Scholar], and that appropriate surgical prophylaxis for joint arthroplasty reduces the risk for PJI for >80% [[2]AlBuhairn B. Hind D. Hutchinson A. Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review.J Bone Jt Surg Ser B. 2008; 90: 915-919Crossref PubMed Scopus (188) Google Scholar]. In The Netherlands and Austria, 50 000 [[9]Online Dutch atrhoplasty register (LROI) annual report. Den Bosch, 2018www.lroi-report.nlGoogle Scholar] and 35 000 [[10]Leitner L. Türk S. Heidinger M. Stöckl B. Posch F. Maurer-Ertl W. et al.Trends and economic impact of hip and knee arthroplasty in Central Europe: findings from the Austrian National Database.Sci Rep. 2018; 8: 4707Crossref PubMed Scopus (17) Google Scholar] new prosthetic joints are implanted, respectively. Using these numbers, around 133 and 93 delayed PJIs could be prevented annually. Roughly, at European levels this number will thus be > 3000 annually. The antibiotic of choice to which S. epidermidis is almost always susceptible is vancomycin, a glycopeptide antibiotic. For surgical prophylaxis, vancomycin is often used as an alternative to cefazolin, when the patient is colonized with, has a high risk for, or has a history of methicillin-resistant S. aureus (MRSA). It is also often used in patients with life-threatening β-lactam allergies. Here, vancomycin is given in a fixed dose of 1–1.5 g, or in a dose adjusted for weight of 10–15 mg/kg [[1]Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar]. Due to a possible high cost of error of allowing the new implanted joint to be colonized with cefazolin-resistant S. epidermidis or coagulase-negative staphylococci, vancomycin is arguably a better antibiotic to use. S. aureus, the most common cause of acute PJI, is also commonly susceptible to vancomycin. However, evidence on the effectiveness of vancomycin or other glycopeptides in preventing delayed PJI is lacking. The limited number of published studies on the effectiveness of vancomycin as surgical prophylaxis did not perform a sub-analysis on the delayed type of PJI. For example, a study with before-and-after design compared 995 patients who received only cefuroxime with 791 who received cefuroxime and teicoplanin (another antibiotic from glycopeptide group) as surgery prophylaxis. They showed that the PJI rate in the group with teicoplanin addition was lower than in the cefuroxime only group (1.3% versus 3.5%) [[11]Tornero E. Garcí-Ramiro S. Martínez-Pastor J.C. Bori G. Bosch J. Morata L. et al.Prophylaxis with teicoplanin and cefuroxime reduces the rate of prosthetic joint infection after primary arthroplasty.Antimicrob Ag Chemother. 2015; 59: 831-837Crossref PubMed Scopus (32) Google Scholar]. This study did not mention delayed PJI specifically due to coagulase-negative staphylococci. There is a relatively old systematic review which included 14 studies, of which three focused on orthopaedic surgery, and concluded that teicoplanin showed similar effectiveness in preventing SSI [[12]Chambers D. Worthy G. Myers L. Weatherly H. Elliott R. Hawkins N. et al.Glycopeptide vs. non-glycopeptide antibiotics for prophylaxis of surgical site infections: a systematic review.Surg Infections. 2010; 11: 455-462Crossref PubMed Scopus (17) Google Scholar]. SSI is often defined as infection that often occurs within 1 month after surgery and does not include delayed PJI. From these publications we can assume that using a glycopeptide as prophylaxis in prosthetic joint surgery is not inferior to cephalosporin alone. Nonetheless, there is also a study showing that patients receiving vancomycin had an odds ratio of 1.6 (95%CI 1.0–2.5) of having PJI compared to patients receiving cefazolin prophylaxis [[13]Kheir M.M. Tan T.L. Azboy I. Tan D.D. Parvizi J. Vancomycin prophylaxis for total joint arthroplasty: incorrectly dosed and has a higher rate of periprosthetic infection than cefazolin.Clin Orthop Relat Res. 2017; 475: 1767-1774Crossref PubMed Scopus (44) Google Scholar]. Yet by looking at this study in depth, as many as 64% of patients who received a fixed 1-g dose of vancomycin were underdosed. Rock-solid evidence will remain difficult to obtain, especially for delayed PJI. A randomized controlled trial on this topic should have a follow-up for 2 years, which is clearly longer than when SSI is considered as an outcome (i.e. 1 year according to the Centers for Disease Prevention and Control). The difficulties in the diagnosis of late PJI may also mean that participation in a study on the effectiveness of vancomycin as surgical prophylaxis in preventing delayed PJI may be only possible for a large centre with a multidisciplinary approach. Were the hypothesis true that vancomycin can reduce delayed PJI more than an antibiotic from the cephalosporin class, then the rate of delayed PJI should be lower in the setting where vancomycin is often used due to a high prevalence of MRSA than in a no/low MRSA setting. Perhaps such cross-country observational studies or before–after studies (i.e. before implementation of vancomycin surgical prophylaxis and after implementation) will give more insight regarding this topic. Another issue regarding vancomycin is the organization of administering surgical prophylaxis. The administration time of vancomycin is different from cephalosporins like cefazolin. Cefazolin is ideally given within 60 min before the incision in order to achieve optimal tissue concentrations [[1]Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar]. By contrast, vancomycin should be given more slowly due to the possibility of red man syndrome. For a dose of 1 g, the infusion should be given at least 60 min before incision, and for the dose of 1.5 g between 60 and 120 min before incision [[1]Tande A.J. Patel R. Prosthetic joint infection.Clin Microbiol Rev. 2014; 27: 302-345Crossref PubMed Scopus (768) Google Scholar]. Vancomycin may be used alone or in combination with another cephalosporin antibiotic, as shown in the above-mentioned study. Since vancomycin also has coverage of other pathogens responsible for PJI, such as S. aureus, MRSA, C. acnes, and enterococci, perhaps it can be used alone. The different timing and the various antibiotics that can be chosen for surgical prophylaxis for various surgical indications may be too complicated for doctors, surgeons, or nurses who are responsible for administering prophylaxis. This may lead to mistakes, poor compliance, or inappropriate timing of administering surgical prophylaxis. Adaptation of surgical prophylaxis organization may be needed when vancomycin is chosen as surgical prophylaxis in prosthetic surgery. The well-known side effect of vancomycin (such as renal toxicity) should also be considered. However, a recent study did not show an additional risk of renal toxicity when vancomycin was used as surgical prophylaxis to prevent PJI [[14]Burger J.R. Hansen B.J. Leary E.V. Aggarwal A. Keeney J.A. Dual-agent antibiotic prophylaxis using a single preoperative vancomycin dose effectively reduces prosthetic joint infection rates with minimal renal toxicity risk.J Arthroplasty. 2018; 33: S213-S218Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Other antibiotics for Gram-positive cocci can also be theoretically considered as alternatives for surgical prophylaxis in prosthetic joint surgery. However, S. epidermidis strains are often resistant to these antibiotics (clindamycin, ciprofloxacin), or they are relatively new and not available as generics: ceftarolin (an anti-methicillin-resistant S. aureus antibiotic) and dalbavancin (a semisynthetic lipoglycopeptide with a spectrum comparable to that of glycopeptide antibiotics). In summary, we argue that vancomycin for surgical prophylaxis in prosthetic surgery may reduce the number of PJIs significantly, especially delayed PJIs. Since the treatment of delayed PJI often involves the removal of the prosthesis, the effect of vancomycin reduces not only the incidence and morbidity but also economic costs. So far, the evidence on the effectiveness of vancomycin is still lacking, and perhaps will remain difficult to obtain. Several studies have shown that vancomycin is not inferior to cephalosporin, but more studies—ideally randomized control trials—are still needed. The number of participants needed must be large (due to the relatively low incidence of late PJI) and the follow-up duration should be at least 2 y. Due to possible complexity, the use of vancomycin should be discussed and balanced with the organization capacity of the hospital in giving timely surgical prophylaxis. The use of vancomycin should be discussed at guideline development level. The authors declare no conflicts of interest. No external funding was received.
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