Bone and Joint Infections: The Role of Imaging in Tailoring Diagnosis to Improve Patients' Care

Imaging is needed for the diagnosis of bone and joint infections, determining the severity and extent of disease, planning biopsy, and monitoring the response to treatment. Some radiological features are pathognomonic of bone and joint infections for each modality used. However, imaging diagnosis of these infections is challenging because of several overlaps with non-infectious etiologies. Interventional radiology is generally needed to verify the diagnosis and to identify the microorganism involved in the infectious process through imaging-guided biopsy. This narrative review aims to summarize the radiological features of the commonest orthopedic infections, the indications and the limits of different modalities in the diagnostic strategy as well as to outline recent findings that may facilitate diagnosis

Which Patients with Chronic Periprosthetic Joint Infection Are Less Suitable to Successful Two Stage Exchange Arthroplasty Surgery? A Retrospective Clinical Trial

Which Patients with Chronic Periprosthetic Joint Infection Are Less Suitable to Successful Two Stage Exchange Arthroplasty Surgery? A Retrospective Clinical Tria

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study—The ARTHR-IS Study Group

Introduction: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. Results: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson >= 2, haemoglobin 30 kg/m(2) and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. Conclusions: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. [GRAPHICS]

Therapeutic Drug Monitoring of Linezolid: a Retrospective Monocentric Analysis▿

The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [Cmin] and peak [Cmax] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC24]). The final database included 280 Cmin and 223 Cmax measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously (n = 58) or orally (n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for Cmin, 14.70 mg/liter [10.57 to 19.64] for Cmax, and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC24). Linezolid Cmin was linearly correlated with estimated AUC24 (r2 = 0.85). Optimal pharmacodynamic target attainment (defined as Cmin of ≥2 mg/liter and/or AUC24/MIC90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as Cmin of ≥10 mg/liter and/or AUC24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure

Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients

OBJECTIVES: Prolonged treatment with linezolid may cause toxicity. The purpose of this study was to define pharmacodynamic thresholds for improving safety outcomes of linezolid. METHODS: We performed a retrospective study of patients who had trough (C(min)) and peak (C(max)) plasma levels measured during prolonged linezolid treatment. Dosage adjustments were performed when C(min) 6510 mg/L and/or AUC\u2082\u2084 65400 mg/L\u200a\ub7\u200ah. Patients were divided into two subgroups according to the absence or presence of co-treatment with rifampicin (the linezolid group and the linezolid\u200a+\u200arifampicin group, respectively). Data on demographic characteristics, disease, microbiology and haematochemical parameters were collected and outcomes in relation to drug exposure were compared between groups. RESULTS: A total of 45 patients were included. Dosage adjustments were needed in 40% versus 0% of patients in the linezolid group (n\u200a=\u200a35) versus the linezolid\u200a+\u200arifampicin group (n\u200a=\u200a10), respectively. Patients in the linezolid group had either significantly higher C(min) [3.71 mg/L (1.43-6.38) versus 1.37 mg/L (0.67-2.55), P\u200a<\u200a0.001] or AUC\u2082\u2084 [212.77 mg/L\u200a\ub7\u200ah (166.67-278.42) versus 123.33 mg/L\u200a\ub7\u200ah (97.36-187.94), P\u200a<\u200a0.001]. Thrombocytopenia appeared in 51.4% versus 0% of cases in the linezolid group versus the linezolid\u200a+\u200arifampicin group, respectively. In 33.3% of those patients who were experiencing thrombocytopenia, therapeutic drug monitoring (TDM)-guided dosage reductions allowed recovery from toxicity and prosecution of therapy with good outcome. A logistic regression model for thrombocytopenia estimated a probability of 50% in the presence of C(min) of 6.53 mg/L and/or of AUC\u2082\u2084 of 280.74 mg/L\u200a\ub7\u200ah. CONCLUSIONS: Maintenance over time of C(min) between 2 and 7 mg/L and/or of AUC\u2082\u2084 between 160 and 300 mg/L\u200a\ub7\u200ah may be helpful in improving safety outcomes while retaining appropriate efficacy in adult patients receiving prolonged linezolid treatment

Implementation and validation of a Bayesian method for accurately forecasting duration of optimal pharmacodynamic target attainment with dalbavancin during long-term use for treating subacute and/or chronic staphylococcal infections

Dalbavancin is being increasingly used for long-term treatment of subacute and/or chronic staphylococcal infections. Here we implemented and validated a new Bayesian model by means of the MwPharm software for accurately forecasting duration of pharmacodynamic target attainment above the efficacy thresholds of 4.02 or 8.04 mg/L against staphylococci. Forecasting accuracy improved substantially with the a posteriori approach compared to the a priori approach, especially when two measured concentrations were used. This strategy may help clinicians in estimating proper duration of optimal exposure with dalbavancin during longterm treatment

Reply to Baklouti et al., "Why Is It Desirable To Do the External Evaluation of a Population Pharmacokinetic Model?"

We thank Baklouti et al. (1) for commenting on our population pharmacokinetic study of dalbavancin for optimal treatment of adult patients with staphylococcal osteoarticular infections (2) and for suggesting that our model tends to underestimate the concentrations observed in a group of French patients (French group).…

Population pharmacokinetics of dalbavancin and dosing consideration for optimal treatment of adult patients with staphylococcal osteoarticular infections

Background: Dalbavancin is gaining interest in the treatment of complex osteoarticular (OA) infections. Objective: To conduct a population pharmacokinetic analysis of dalbavancin in a prospective cohort of adult patients with Gram-positive OA infections and to identify optimal dosing regimens for long term-treatment. Methods: Non-linear mixed-effects modelling was performed with Monolix. Monte Carlo simulations were performed with six dalbavancin regimens (1500mg at day 1; 1000mg at day 1 plus 500mg at day 8; 1500mg at day1 and 8; 1500mg at day1 and 8 plus 500, 1000 or 1500mg at day 36) to assess the PTA of three pharmacodynamic target of fAUC24h/MIC against S. aureus (&gt;27.1, 53.3 and 111.1). Cumulative fraction of response (CFR) was calculated against MIC distribution of both MRSA and MSSA as well. Desirable PTAs and CFRs were 6590%. Results: Fifteen patients provided 120 plasma concentrations. Most (73.3%) had prosthetic joint infections. Clinical cure rate was 87%. A two-compartment model with linear elimination well described the data. No covariate was retained in the final model. Pharmacokinetic dalbavancin estimates were 0.106L/h for CL and 36.4L for Vss. The tested dosing regimens granted desirable CFRs against S. aureus at the most effective PK/PD target for a period ranging 3-to-9 weeks. Conclusion: Giving a two 1500mg dosing regimen of dalbavancin one week apart may ensure efficacy against both MSSA and MRSA up to 5 weeks in patients with OA infections. Clinical assessment at that time may allow for considering whether or not an additional dose should be administered for prolonging effective treatment

Spine Infections: The Role of Fluorodeoxyglucose Positron Emission Tomography (FDG PET) in the Context of the Actual Diagnosis Guideline

Spondylodiscitis is an infectious process that requires numerous health care professionals to be clearly diagnosed and eventually successfully treated. It implies a variety of microbiological agents and conditions; during the diagnostic workup, it is difficult to correctly identify them, and the clinician has to rapidly choose the correct treatment to avoid permanent injuries to the patient. In this context, we conducted a review to better understand the most suitable use of Positron Emission Tomography with 18-Fluoro-deossi-glucose (FDG PET) in a patient suspected of spondylodiscitis, based on current guidelines and literature.. We wanted to review the role of FDG PET in the spondylodiscitis diagnosis and follow up in the context of the current guidelines