Prosthetic-Joint Infections — NEJM

The patients history, labs, and imaging are consistent with an infected total joint prosthesis

Antibiotics, alternatives and natural - Ray Sahelian

ic Valve Endocarditis: Because prosthetic valve staphylococcal endocarditis has a high mortality, combination therapy seems prudent. It is clearly associated with better bacteriological outcomes (). The addition of and to the beta-lactam or is most commonly recommended, although controlled studies have not been done. Gentamicin should be given for 2 weeks rather than for 3 to 5 days as with native valve endocarditis. A favorable response of MRSA prosthetic valve endocarditis to therapy after unsuccessful treatment with vancomycin has been reported (). Because of the very limited clinical data, minocycline should probably be regarded as an alternative agent for MRSA endocarditis. Daptomycin or combinations using daptomycin might be considered, although no data exist to support this option. Survival is probably more dependent on whether valve replacement surgery can be performed than on the choice of antibiotic regimen (,). Recent evidence favours ceasing rather than continuing with anticoagulant treatment to reduce morbidity from cerebral events ().

Prosthetic-joint replacement is used increasingly to alleviate pain and to improve mobility

Antibiotics alternatives, how well do they work

Following this great success, there are also some failures of arthroplasty, which lead to operative revision. In 2000, there were 28,000 revision THAs and 31,000 revision TKAs performed in US and each year, more than one billion dollars are spent there on THA and TKA revisions. Causes that lead to failure of arthroplasty might include aseptic loosening, dislocations, prosthesis infections, massive bone loss, fractures and metal allergy., After total joint replacement operations, the total infection rates of the implants are reported to be less than 1%,, and the patients with rheumatoid arthritis could have a higher infection rate of up to 3.7%. However, bacterial infection of a joint prosthesis is a severe complication that is currently difficult to cure with antibiotic treatment. In most cases, the infected prosthesis implant has to be removed in order to cure the infection. It is, therefore, important, and necessary, to improve our understanding of the pathogenesis of prosthesis infections after orthopedic joint replacement.

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.