Prosthesis-related infections after joint replacement are disastrous for patients because, in most cases, removal of the infected prosthesis is the only way to cure the infection. It becomes, therefore, important to prevent prosthesis infection. The pathogenesis of prosthesis-related infections could be explained by the interactions of three basic factors, i.e. the number of invading bacteria and their virulence, the host’s immune responses, and the properties of the implant materials.
Bacterial infection in prosthesis can easily result in wound sepsis and failure of the joint replacement. Therefore, joint replacements require an ultra-clean environment for surgery. Because of the risk factors mentioned in points above, antibiotic prophylaxis is recommended; this should be applied systemically four times a day on the day of surgery and in combination with the application of cementcontaining antibiotic substance. This measure has been demonstrated to be efficient in minimizing the risk of infection. The details are discussed below (Prophylaxis of the prosthesisrelated infections).
SUMMARY Prosthetic joint infection (PJI) ..
Prostheses-related infections are now thought to be biofilm-associated infections,,, which are highly resistant to antibiotic treatment. The mechanisms for the biofilm bacterial cells to become resistant to antibiotics are not fully understood. It is believed that in addition to conventional resistance mechanisms such as beta-lactamase and efflux pumps,, poor antibiotic penetration, nutrient limitation, slow growth, adaptive stress responses and formation of persister cells are involved. In addition, in vitro and in vivo studies of antibiotic pharmacokinetics/pharmacodynamics in bacterial biofilms have indicated that, biofilm bacteria are significantly more resistant than their planktonic counterparts, and antibiotic treatment, therefore, requires a higher dose and combination., It is, therefore, not recommended to treat implant infections with antibiotics only. On the basis of appropriate surgical intervention, if the clinical signs and symptoms of implant infection have been observed for less than three weeks, the implant is stable and the surrounding tissue is in a good condition, antibiotic treatment becomes crucial. Due to the integrated resistance of bacterial biofilm, it is important to choose highly active, better penetrating and combined antibiotic treatment. For the infections caused by staphylococci, Zimmerli et al. performed a randomized, placebo-controlled, double-blind clinical trial on 33 patients with proven staphylococcal infection and stable orthopedic implants from 1992 through 1997. They found that patients treated with initial debridement and 2-week intravenous flucloxacillin (2 g q.i.d. for methicillin- sensitive) or vancomycin (1 g b.i.d. for methicillin-resistant) together with rifampin (450 mg p.o., b.i.d.), followed by three (hip implants) or six (knee implants) months of ciprofloxacin (750 mg p.o., b.i.d.) and rifampin treatment had a 100% cure rate compared with the ciprofloxacin-placebo group (58% cure rate). It is, therefore, recommended to treat staphylococcal implant infections with 2-4 weeks intravenous beta (β)-lactam (for methicillin- sensitive) or glycopeptide (for methicillin- resistant) in combination with rifampicin to minimize the bacterial burden and risk of antibiotic resistance, followed by long-term rifampicin (450 mg p.o. b.i.d.) and levofloxacin (750 mg p.o., q.d. to 500 mg b.i.d.) or other fluoroquinolones.,, For details, please refer to the new protocol of antibiotic treatment up-dated in 2012 by Zimmerli et al. Application of the combination with rifampicin (20 mg/kg) and fluoroquinolone showed good results in a French clinical study. Fusidic acid was recently recommended as an efficient antibiotic for the treatment of bone and joint infections caused by S. aureus and MRSA. In our clinical practice, cefuroxim 1.5 g i.v., t.i.d. and fusidic acid (Fucidin) 500 mg p.o., t.i.d. are used as initial treatment followed by dicloxacillin 1g p.o., q.i.d. together with fucidin 500 mg p.o., t.i.d. or rifamicin 600 mg p.o., b.i.d. for the treatment of Staphylococcus aureus infection. For methicillin-resistant staphylococal infections, vancomycin 1g i.v., b.i.d and fucidin or rifampicin p.o. are applied initially followed by rifampicin and fucidin or moxifloxacin 400 mg p.o., q.d. or linezolid 600 mg p.o. b.i.d. according to the sensitivity results. Spanish colleagues recently reported that combination treatment with rifampicin and linezolid showed a 69.4% success rate (34 of 49 patients) for prosthetic joint infection with retention of the implant after two years. Recently, daptomycin has also been recommended as a new option for the treatment of implant infections, due to its good effect systemically and locally against methicillin-resistant staphylococci and enterococci in patients with implant-associated infections., By using such antibiotic treatment, prosthetic knee-associated infections in many patients could be well controlled. Soriano et al., in a study of 85 patients with orthopedic implant infections, reported that 47- and 60-day treatment with linezolid showed a 72.2% and a 42.8% success rate in acute and chronic infections, respectively, when the implant was not removed. However, in a clinical study of 112 patients with prosthetic joint infection carried out in the UK, arthroscopic debridement and empirical treatment with vancomycin 1g i.v. every 12 h, plus meropenem 500 mg i.v. t.i.d. for inpatients and ceftriaxone 1 g i.v. q.d. plus teicoplanin 400 mg i.v. q.d. for outpatients, followed by oral rifampicin and quinolones could not avoid failure (18% recurred infection over 2.3 years). The authors concluded that antibiotic therapy may simply postpone, rather than prevent failure. But arthroscopic debridement might not be sufficient to remove the infected tissue, and, in our opinion, the doses of meropenem and ceftriaxone used in the study were too low.