Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

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Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children

Purpose of reviewWe review recent advances in the prevention, diagnosis and treatment of infections associated with joint prostheses and internal fixation devices.Recent findingsThe perioperative antimicrobial prophylaxis should be administered 60–30 min before incision or before inflation of the to

Infections associated with orthopedic implants.

The standard recommendation for treating chronic osteomyelitis is 6 weeks of parenteral antibiotic therapy. However, oral antibiotics are available that achieve adequate levels in bone, and there are now more published studies of oral than parenteral antibiotic therapy for patients with chronic osteomyelitis. Oral and parenteral therapies achieve similar cure rates; however, oral therapy avoids risks associated with intravenous catheters and is generally less expensive, making it a reasonable choice for osteomyelitis caused by susceptible organisms. Addition of adjunctive rifampin to other antibiotics may improve cure rates. The optimal duration of therapy for chronic osteomyelitis remains uncertain. There is no evidence that antibiotic therapy for >4–6 weeks improves outcomes compared with shorter regimens. In view of concerns about encouraging antibiotic resistance to unnecessarily prolonged treatment, defining the optimal route and duration of antibiotic therapy and the role of surgical debridement in treating chronic osteomyelitis are important, unmet needs.

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Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults

Antibacterials play a key role in the treatment of bone infections and appropriate surgical prophylaxis. The rate and extent of penetration of antimicrobials into bone has been assessed and shown to be important for successful treatment in numerous studies. However, no recent review or critical evaluation of the analytical techniques is available. This review compares established and new sample preparation and analytical methods to measure bone concentrations. We performed a systematic literature search in MEDLINE, EMBASE, conference abstracts and references from published articles on bone penetration of antibacterials. This article focuses on the standardization of drug analysis in bone, the extent and rate of bone penetration of antibacterials, and the design, evaluation and reporting techniques of pharmacokinetic studies of bone penetration. The focus is on studies conducted between 1998 and 2007, since a previous review was published in 1999. WinNonlin® Professional version 5.0.1 software was used for statistics. Very different methods for sample preparation, drug analysis, data handling and reporting have been employed in bone penetration studies. There is substantial variability in the reported mean bone penetration between drugs and between different studies of the same drug. Quinolones, macrolides and linezolid have mean bone:serum concentration ratios that are commonly between 0.3 and 1.2, and higher ratios have been found for azithromycin (bone concentration in mg/kg of total bone). The ratios are usually between 0.15 and 0.3 for cephalosporins and glycopeptides, and between 0.1 and 0.3 for penicillins. Cephalosporins and penicillins have shown significantly lower (p<0.05) concentration ratios than linezolid. For 20 of 25 different drugs, the ratios were higher for cancellous bone than for cortical bone. The available data show a larger extent of bone penetration for quinolones, macrolides and linezolid than for β-lactams. The bone penetration of penicillins and cephalosporins was significantly lower than that of linezolid. Guidelines on sample preparation, drug analysis, study design and pharmacokinetic evaluation of bone penetration studies are vitally needed.

Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamic and bioanalytical considerations.

Introduction
Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management.

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Spinal infection: state of the art and management algorithm.

Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. Treatment of these infections can be difficult, usually involving a prolonged course of antibiotics, often with surgical intervention. The selection of antibiotics depends on sensitivity profile, patient tolerance and long-term goals, e.g. cure or suppression, but there are few randomized con- trolled trials in patients comparing efficacy of different antibiotics. Different degrees of bone penetration and clinical outcome for specific antibiotics, e.g. the β-lactams, clindamycin and quinolones, have been described, although the methodology in these studies is not standardized and findings cannot always be applied directly to patients. The effect of attaining minimum serum bactericidal concentrations in patients has also been studied but this is no longer routinely recommended in clinical practice. Comparative clinical trials are few but have demonstrated efficacy of oral fluoroquinolones in combination with either rifampicin or fusidic acid for selected Gram-positive infections. In the past decade, increasingly resistant organisms, e.g. methicillin- resistant Staphylococcus aureus and vancomycin-resistant enterococci have been recognized as causes of orthopaedic infection. Individual case reports describe successful treatment using the newer antibiotics, e.g. linezolid and quinupristin/dalfopristin, but results of clinical trials are awaited.

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Antibiotic treatment of gram-positive bone and joint infections.

Background: Debridement, antibiotics and implant retention (DAIR) forms the primary treatment modality for early prosthetic joint infection (PJI). The KLIC score has been proposed as a risk stratification tool for use in predicting outcome of prosthetic knee infections. Our aim was to determine the accuracy of this scoring system at an independent tertiary PJI centre in a typical DAIR population. Methods: Between 2008 and 2015, patients with infected knee prostheses treated with DAIR were identified. The patient notes and blood tests were reviewed retrospectively and the 'KLIC-score' was calculated and correlated with outcome. The end point for early failure was defined as: 1) the need for unscheduled surgery, 2) infection-related death ≤12 months from debridement or 3) the need for suppressive antibiotic treatment. Results: 59 patients received DAIR procedures for knee PJI. Treatment was successful in 41 patients (69%) with early failure in 18 patients (31%). Patients deemed high-risk (KLIC-score ≥7) had notably higher failure rates (60%) than those scoring <7 (28%). No relationship can be drawn between KLIC-scores of <7 and failure rates. Conclusions: The KLIC-score applied retrospectively was able to predict patients with the highest risk of early failure but provides little information in patients with scores of <7.

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Analysis Of The KLIC-score; An Outcome Predictor Tool For Prosthetic Joint Infections Treated With Debridement, Antibiotics And Implant Retention

Sir, We have noted with interest the points made by Frippiat et al. and make the following comments. We have not stated that the newer quinolones should not be considered for treatment of Gram-positive bone and joint infections. We agree that this group of antibiotics offers an attractive alternative to standard parenteral therapy because of their potency against Gram-positive pathogens and good bioavailability, but caution that the safety of the newer quinolones in long-term use is not yet established. There is a lack of clinical experience and data regarding long-term outcome with these agents treating chronic infections in man, compared with older fluoroquinolones. Quinolone resistance is increasing; the development of resistance to the new fluoroquinolones in Gram-positive organisms has been reported in a pharmacodynamic study, and Frippiat et al. also refer to a clinical case where resistance developed in one of seven of their patients treated for Grampositive prosthetic joint infection. In agreement with Frippiat et al., our advice to clinicians is that until there are more clinical data available, the addition of a second antibiotic (often rifampicin) should be considered when using a quinolone to treat deep infection, over a prolonged duration. The optimum dose of rifampicin for use as a second agent in treatment of orthopaedic infection has not been identified, although bone penetration studies have suggested that 600 mg twice daily will give optimal bone concentrations when compared with 300 mg twice daily or 600 mg daily. We usually recommend a dose between 300–600 mg twice daily, depending on the size of the patient and the causal pathogen. This dose is comparable to the dose of 10–20 mg/kg/day suggested by Frippiat et al. Finally, we agree that whereas linezolid is an attractive option for oral treatment of MRSA and other multi-resistant Gram-positive infection, it is not recommended for use in chronic infection, such as osteomyelitis, due to the lack of safety data when used for >28 days. We have not yet encountered optic neuropathy in association with prolonged linezolid treatment, but have observed thrombocytopenia in some patients, a recognized side effect, and advise clinicians to monitor full blood count weekly when prescribing linezolid for both inpatients and outpatients. References

Elizabeth S. R. Darley

Papers

Antibiotic treatment of gram-positive bone and joint infections.

Analysis Of The KLIC-score; An Outcome Predictor Tool For Prosthetic Joint Infections Treated With Debridement, Antibiotics And Implant Retention

Treatment of Gram-positive bone and joint infection: authors' response

Extended Spectrum β Lactamase (ESBL) producing bacteria in a large UK NHS Hospital Trust

Vancomycin efficacy (MIC and Bactericidality) in Clinical Outcome in Patients with Methicillin Resistant Staphylococcus Aureus (MRSA) Bacteraemia