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Orthopaedic Surgery: Optimizing Antibiotic Therapy through Evaluation of Local Antibiotic...
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Orthopaedic Surgery: Optimizing Antibiotic Therapy through Evaluation of Local Antibiotic Bone- and Soft Tissue Concentrations

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 12709

Special Issue Editors

Dr. Mats Bue

E-Mail Website
Guest Editor
Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Interests: sampling of bone- and soft tissue concentrations of various antibiotics under different orthopedically relevant settings by use of microdialysis
Dr. Maiken Stilling

E-Mail Website
Guest Editor
Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Interests: sampling of bone- and soft tissue concentrations of various antibiotics under different orthopedically relevant settings by use of microdialysis

Special Issue Information

Dear Colleagues,

We administer a lot of antibiotics to our patients—let us do it the best possible way!

Antibiotics must reach the target site, i.e., the site of infection or where infection is to be avoided, in sufficient concentration and for an adequate amount time to have an effect. Plasma values are often used as surrogate markers for tissue concentrations, and thus for sufficiency of the antibiotic therapy. However, due to different molecular size, chemical structure, etc., antibiotics present different tissue pharmacokinetic profiles, which, furthermore, also depend on the dosage and way of administration, i.e., intravenous (bolus, intermittent or continuous), oral, intramuscular or local. Moreover, the opted ideal antibiotic tissue pharmacokinetic profile relies on the efficacy of the specific antibiotic (e.g., time-dependent and concentrations-dependent killing). These considerations and information are extremely important for the treating health physician and should be included in every antibiotic therapy regimen.

Although methodological improvements have occurred over the recent years, the determination of antibiotic tissue concentrations remains challenging because no gold standard exist to validate the findings. Bone is unique and heterogenous , and behaviour highly depends on the physiological or pathological state of the bone, such as in the case of bone fracture, bone infection or presence of an implant. This Special Issue focuses on optimizing the current antibiotic therapy in orthopaedic surgery by evaluating local antibiotic bone and soft tissue concentrations. The issue will consist of 10–15 manuscripts, which may include original research, review articles, case series and opinion papers. We are interested in both qualitative research and quantitative research that provide tools for professionals and individuals to responsibly use antimicrobials.

Dr. Mats Bue
Dr. Maiken Stilling
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotic tissue concentrations
  • antibiotic bone concentrations
  • microdialysis
  • bone specimens
  • tissue specimens
  • antibiotic prophylaxis
  • antibiotic treatment
  • orthopaedic surgery

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Published Papers (4 papers)

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Research

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10 pages, 1112 KiB  
Article
Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study
by Johanne Gade Lilleøre, Andrea René Jørgensen, Martin Bruun Knudsen, Pelle Hanberg, Kristina Öbrink-Hansen, Sara Kousgaard Tøstesen, Kjeld Søballe, Maiken Stilling and Mats Bue
Antibiotics 2023, 12(3), 615; https://doi.org/10.3390/antibiotics12030615 - 20 Mar 2023
Viewed by 1509
Abstract
Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic [...] Read more.
Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference. For the low piperacillin target (8 µg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54–74%) was found. For the high target (16 µg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49–54%), and similar between the two cancellous bone compartments. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered. Full article
(This article belongs to the Special Issue Orthopaedic Surgery: Optimizing Antibiotic Therapy through Evaluation of Local Antibiotic Bone- and Soft Tissue Concentrations)
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11 pages, 1912 KiB  
Article
Piperacillin Steady State Concentrations in Target Tissues Relevant for PJI Treatment—A Randomized Porcine Microdialysis Study Comparing Continuous Infusion with Intermittent Short-Term Infusion
by Hans Christian Rasmussen, Pelle Hanberg, Martin Knudsen, Sara Kousgaard Tøstesen, Andrea René Jørgensen, Elisabeth Krogsgaard Petersen, Kristina Öbrink-Hansen, Kjeld Søballe, Maiken Stilling and Mats Bue
Antibiotics 2023, 12(3), 577; https://doi.org/10.3390/antibiotics12030577 - 14 Mar 2023
Cited by 1 | Viewed by 1955
Abstract
(1) Introduction: Piperacillin is a common antibiotic choice in the treatment of periprosthetic joint infections (PJI) caused by Pseudomonas aeruginosa. The aim of this study was to assess and compare the time with free piperacillin concentration above the minimum inhibitory concentration ( [...] Read more.
(1) Introduction: Piperacillin is a common antibiotic choice in the treatment of periprosthetic joint infections (PJI) caused by Pseudomonas aeruginosa. The aim of this study was to assess and compare the time with free piperacillin concentration above the minimum inhibitory concentration (fT > MIC) at steady state in target tissues relevant for PJI treatment following continuous and intermittent short-term infusion. (2) Methods: 16 pigs were randomized to receive either continuous or intermittent short-term infusion of piperacillin. Steady state piperacillin concentrations were assessed using microdialysis in tibial cortical bone, tibial cancellous bone, synovial fluid of the knee joint, and subcutaneous tissue. MIC-targets of 4, 8, 16, and 64 mg/L were applied. Plasma samples were obtained as reference. (3) Results: Continuous infusion resulted in longer fT > MIC for MIC targets of 4 mg/L and 8 mg/L compared to intermittent short-term infusion in all compartments with the exception of tibial cortical bone. For the MIC-target of 16 mg/L, continuous infusion resulted in a longer fT > MIC in all compartments except for the bone compartments. No differences between groups were seen when applying a MIC-target of 64 mg/L. (4) Conclusions: An aggressive dosing strategy may be necessary to obtain sufficient piperacillin concentrations in all bone compartments, particularly if more aggressive targets are applied. Based on the present study, continuous infusion should be considered in the treatment of PJI. Full article
(This article belongs to the Special Issue Orthopaedic Surgery: Optimizing Antibiotic Therapy through Evaluation of Local Antibiotic Bone- and Soft Tissue Concentrations)
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Review

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20 pages, 3221 KiB  
Review
Local Antibiotic Delivery Options in Prosthetic Joint Infection
by William Steadman, Paul R. Chapman, Michael Schuetz, Beat Schmutz, Andrej Trampuz and Kevin Tetsworth
Antibiotics 2023, 12(4), 752; https://doi.org/10.3390/antibiotics12040752 - 14 Apr 2023
Cited by 25 | Viewed by 4853
Abstract
Prosthetic Joint Infection (PJI) causes significant morbidity and mortality for patients globally. Delivery of antibiotics to the site of infection has potential to improve the treatment outcomes and enhance biofilm eradication. These antibiotics can be delivered using an intra-articular catheter or combined with [...] Read more.
Prosthetic Joint Infection (PJI) causes significant morbidity and mortality for patients globally. Delivery of antibiotics to the site of infection has potential to improve the treatment outcomes and enhance biofilm eradication. These antibiotics can be delivered using an intra-articular catheter or combined with a carrier substance to enhance pharmacokinetic properties. Carrier options include non-resorbable polymethylmethacrylate (PMMA) bone cement and resorbable calcium sulphate, hydroxyapatite, bioactive glass, and hydrogels. PMMA allows for creation of structural spacers used in multi-stage revision procedures, however it requires subsequent removal and antibiotic compatibility and the levels delivered are variable. Calcium sulphate is the most researched resorbable carrier in PJI, but is associated with wound leakage and hypercalcaemia, and clinical evidence for its effectiveness remains at the early stage. Hydrogels provide a versatile combability with antibiotics and adjustable elution profiles, but clinical usage is currently limited. Novel anti-biofilm therapies include bacteriophages which have been used successfully in small case series. Full article
(This article belongs to the Special Issue Orthopaedic Surgery: Optimizing Antibiotic Therapy through Evaluation of Local Antibiotic Bone- and Soft Tissue Concentrations)
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Other

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9 pages, 6167 KiB  
Case Report
Mycobacterium marinum: A Challenging Cause of Protracted Tenosynovitis
by Pernille Grand Moestrup, Maiken Stilling, Christian Morberg Wejse and Victor Naestholt Dahl
Antibiotics 2023, 12(3), 629; https://doi.org/10.3390/antibiotics12030629 - 22 Mar 2023
Cited by 3 | Viewed by 3856
Abstract
Mycobacterium marinum infections are rare, and they can be difficult to diagnose and treat. This may lead to further spread of the infection and complications, such as tenosynovitis, pyomyositis, and osteomyelitis. A 40-year-old previously healthy man presented with tenosynovitis of the extensor tendons [...] Read more.
Mycobacterium marinum infections are rare, and they can be difficult to diagnose and treat. This may lead to further spread of the infection and complications, such as tenosynovitis, pyomyositis, and osteomyelitis. A 40-year-old previously healthy man presented with tenosynovitis of the extensor tendons on the second phalanx of his right hand. He was initially treated with steroid injections without any effect. Followingly, ulceration and an abscess developed on the dorsal site of the hand. At this point, it came to the physician’s knowledge that the patient had been cleaning an aquarium before onset of symptoms. After progression to massive tenosynovitis, the patient was admitted and underwent multiple surgical debridements. Briefly, after the first surgery, an interferon-γ release assay was positive, and treatment for M. marinum with rifampicin and azithromycin was initiated after eight months of symptoms. Later, a surgical biopsy showed acid-fast bacilli, and a polymerase chain reaction confirmed the diagnosis of M. marinum. In this case story, we highlight the difficulties of diagnosing and managing this complicated infection, describe the considerable morbidity associated with it, and suggest that local tissue concentrations could be useful to improve clinical outcomes, as these concentrations are potentially suboptimal. Full article
(This article belongs to the Special Issue Orthopaedic Surgery: Optimizing Antibiotic Therapy through Evaluation of Local Antibiotic Bone- and Soft Tissue Concentrations)
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