Summary Objectives A main determinant of clinical response to antibiotic treatment is drug concentration at the infected site. Data on ceftriaxone (CFX) bone penetration are lacking. We measured CFX ...concentrations in infected bone to verify their relationship with pharmacodynamic microbiological markers. Methods Eleven patients undergoing debridement for septic non-union of the tibia and receiving intravenous CFX were studied. Plasma and bone specimens were collected intraoperatively at a variable interval after CFX administration. Drug concentrations were measured by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method. Results Bone samples were extracted at a mean of 3.3 h (range 1.5–8.0 h) since the start of CFX infusion. The mean ± standard deviation intraoperative CFX plasma concentration was 128.4 ± 30.8 mg/l; the corresponding bone concentrations were 9.6 ± 3.4 mg/l (7.8%) in the cortical compartment and 30.8 ± 8.6 mg/l (24.3%) in the cancellous compartment. The mean 24-h area under the concentration–time curve (AUC24 ) values were 176.8 ± 62.2 h*mg/l in cortical bone and 461.5 ± 106.8 h*mg/l in cancellous bone. The time above the minimum inhibitory concentration (T>MIC) was 24 h in all compartments. The estimated mean free AUC/MIC ratios and T>MIC were 140 and 24.4 h, respectively, in cancellous bone and 42.4 and 21 h, respectively, in cortical bone. Conclusions CFX bone penetration was poor (<15%) in the cortical compartment and satisfactory in the more vascularized cancellous bone. The T>MIC and AUC/MIC ratios suggest that CFX achieves a satisfactory pharmacokinetic exposure in cancellous bone as far as pathogens with a MIC of <0.5 are concerned. However, considering free drug concentrations, pharmacokinetic/pharmacodynamic targets may not be fully achieved in cortical bone. As antibiotic exposure can be suboptimal in the infected cortical compartment, and drug penetration may be impaired into necrotic bone and sequesters, a radical surgical removal of purulent and necrotic tissues appears essential to shorten treatment duration and to prevent treatment failures.
Non-union (NU) of bones is a multifactorial phenomenon. Infected non-unions and/or those with bone loss require “biological treatment”, such as the excision of the pathological infected non-union ...site or the “creation” of new bone substance by the use of distraction techniques.
The treatment of choice that meets both the biological and mechanical requirements is that of the external fixation, in as much as it has an extremely low septic complication rate and the mechanical environment can be varied automatically or programmed depending on the requirements.
The authors report on a total of 287 cases of non-union treated with external fixation, with a 93% success rate.
In the treatment of bone infections, a major determinant of the clinical response is the active drug concentration at the infected site. Because of the high prevalence of meticillin ...(methicillin)-resistant staphylococci and enterococci, glycopeptides are widely used for the treatment of bone and joint infections, but data on their penetration into human bone are lacking. The aim of our study was to measure vancomycin and teicoplanin concentrations in infected human bone under steady-state conditions and verify their relationship with inflammatory markers, patient demographic characteristics and pharmacodynamic microbiological markers.
Twenty-seven adult orthopaedic patients undergoing surgical debridement for septic pseudoarthrosis of the tibia and receiving either intravenous vancomycin (Vancocina) 1 g twice daily) or teicoplanin (Targosid) 10 mg/kg/day) were studied from January 2004 to January 2008. Plasma and bone specimens were simultaneously collected during surgery for pharmacokinetic and microbiological assays at a variable interval after antimicrobial administration. Bone samples were dissected into cortical and cancellous bone, cleaned of soft tissues, crushed and eluted into phosphate buffer. Necrotic samples and sequestra were not analysed.Plasma and bone antimicrobial concentrations were measured by a validated method of high-performance liquid chromatography with UV detection, and bone/plasma concentration ratios were calculated. Cortical and cancellous bone area under the concentration-time curve (AUC) over 24 hours (AUC(24)) values were measured by the linear-log trapezoidal rule, using WinNonlin) software, and were compared with the minimum inhibitory concentrations (MICs) of the infecting agents.
For vancomycin, the mean +/- SD concentrations were 2.66 +/- 1.2 mg/L in cortical bone and 11.53 +/- 7.8 mg/L in cancellous bone (corresponding to 20.67% and 89.39% of intraoperative plasma concentrations), and the mean +/- SD tissue AUC(24) values were 55.15 +/- 25.26 h . mg/L for cortical bone and 299.16 +/- 299.54 h . mg/L for cancellous bone. For teicoplanin, the mean +/- SD concentrations were 2.01 +/- 1.7 and 7.51 +/- 7.0 mg/L in cortical and cancellous bone, respectively (12.35% and 48.6% of intraoperative plasma concentrations), and the mean +/- SD teicoplanin tissue AUC(24) values were 34.08 +/- 23.6 h . mg/L and 155.17 +/- 132.8 h . mg/L for cortical bone and cancellous bone, respectively. The mean vancomycin AUC(24)/MIC ratios were 215.02 for plasma, 47.14 for cortical bone and 268.95 for cancellous bone. The mean teicoplanin AUC(24)/MIC ratios were 336.48, 36.27 and 197.21 for plasma, cortical bone and cancellous bone, respectively.
Bone penetration of both glycopeptides ranged from poor (<15%) to satisfactory (15-30%) in the cortical compartment, while it was far higher into the highly vascularized cancellous tissue. Vancomycin bone penetration was slightly higher than with teicoplanin, but the difference was not statistically significant. Higher bone concentrations were observed with higher inflammatory markers, possibly as a result of increased vascularization and vascular permeability under inflammatory conditions. Bone concentrations over the MIC and AUC/MIC ratios suggested that both glycopeptides achieve a satisfactory pharmacokinetic exposure in the cancellous bone, as far as Gram-positive pathogens are concerned. On the other hand, cortical bone exposure was suboptimal in most patients. Furthermore, as antimicrobial penetration may be affected by impaired blood supply, the role of radical surgical removal of purulent and necrotic tissues appears to be essential in order to shorten treatment duration and to reduce the risk of treatment failure.
Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the ...food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).
Artificial intelligence (AI) has proved to be of great value in diagnosing and managing Sars-Cov-2 infection. ALFABETO (ALL-FAster-BEtter-TOgether) is a tool created to support healthcare ...professionals in the triage, mainly in optimizing hospital admissions.
The AI was trained during the pandemic's “first wave” (February-April 2020). Our aim was to assess the performance during the “third wave” of the pandemics (February-April 2021) and evaluate its evolution. The neural network proposed behavior (hospitalization vs home care) was compared with what was actually done. If there were discrepancies between ALFABETO's predictions and clinicians' decisions, the disease's progression was monitored. Clinical course was defined as “favorable/mild” if patients could be managed at home or in spoke centers and “unfavorable/severe” if patients need to be managed in a hub center.
ALFABETO showed accuracy of 76%, AUROC of 83%; specificity was 78% and recall 74%. ALFABETO also showed high precision (88%). 81 hospitalized patients were incorrectly predicted to be in “home care” class. Among those “home-cared” by the AI and “hospitalized” by the clinicians, 3 out of 4 misclassified patients (76.5%) showed a favorable/mild clinical course. ALFABETO’s performance matched the reports in literature.
The discrepancies mostly occurred when the AI predicted patients could stay at home but clinicians hospitalized them; these cases could be handled in spoke centers rather than hubs, and the discrepancies may aid clinicians in patient selection. The interaction between AI and human experience has the potential to improve both AI performance and our comprehension of pandemic management.
Among forbidden substances included in the European Union legislation, endogenous steroids constitute a challenge in the framework of veterinary Official Monitoring Plans. They can be naturally ...present in body fluids at variable levels depending on the species, sex and age of the animals. Considering the significant advances achieved in breeding conditions and in the selection of producing traits in meat cattle, the aim of this study was to verify by analytical method, in veal calves housed under controlled conditions, if the level of natural steroids hormones assumed as physiological are still actual. The second aim of the study was to verify if the normal histological pattern of growth promoters in target organs is influenced accordingly. Bovine male sex organs are currently analysed in the frame of the Italian histological plan to monitor illicit treatments trend, highlighting microscopic, induced alterations. The levels of 17β-estradiol and progesterone residues resulted under the Limit of Quantitation of the approved official methods and the level of testosterone resulted below the level stated in the Italian Ministerial Decree in force. Male target organs appeared within the limits of the standard histological features.
Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the ...food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).
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