Short communicationLinezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections☆
Introduction
In patients with diabetes, serious complications such as peripheral neuropathy combined with bacterial foot infections account for a large number of hospital stays and are a major cause of non-traumatic amputations of the lower limb. Appropriate management of these complications often requires intravenous (i.v.) administration of potent antimicrobial agents supported by surgical intervention. However, measures like these require co-ordinated interdisciplinary work between surgeons, clinicians, clinical pharmacologists and microbiologists because of uncertainty regarding resistance rates, rapidly evolving outbreaks of multiresistant bacterial strains following long-term therapy with broad-spectrum antibiotics, and incomplete knowledge of drug tissue penetration. Thus, choosing the right antimicrobial agent is essential in these situations.
Linezolid has demonstrated potent in vitro activity against problematic bacteria such as meticillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-resistant Gram-positive bacteria [1]. The ability of linezolid to penetrate into the extracellular space fluid of soft tissues is well documented in healthy volunteers and critically ill patients [2], [3]. However, the rate and extent of penetration of linezolid into bone tissue is controversial in the medical literature [4], [5], [6], [7].
Thus, in the present study we aimed to determine the ability of linezolid to penetrate into bone and the interstitium of inflamed subcutaneous adipose tissue in a small representative cohort of diabetic patients suffering from severe diabetic foot infection (DFI). Recently, the microdialysis technique, which was used in this study, was also employed to assess unbound concentrations of linezolid in cancellous bone tissue of healthy pigs as well as fosfomycin concentrations in healthy and inflamed tissue of diabetic patients presenting with bacterial foot infections complicated by osteomyelitis [7], [8].
Section snippets
Subjects and methods
This study was performed at the Division of Plastic Surgery, Department of Surgery, Landeskrankenhaus Universitätsklinikum Graz (State Hospital University Clinic of Graz, Graz, Austria). Analytical work was performed at the laboratory of J&P Medical Research Ltd. (Vienna, Austria).
Results
No adverse events related to the study drug or to the microdialysis procedure were observed. Key pharmacokinetic parameters of linezolid in healthy and inflamed subcutaneous adipose tissue and in metatarsal bone are summarised in Table 1. Pharmacokinetic profiles are depicted in Fig. 1.
The degree of tissue penetration as expressed by the free (f) tissue to plasma ratios of the AUC from 0–12 h (fAUC0–12tissue/fAUC0–12plasma) was 1.32 ± 0.09, 1.12 ± 0.22 and 1.09 ± 0.11 for healthy subcutis, inflamed
Discussion
MRSA infections associated with unfavourable outcomes are becoming increasingly problematic in diabetic foot clinics [10]. As moderate-to-severe DFI is frequently linked to osteomyelitis of adjacent bones, the ability of certain antibiotic agents to penetrate bone tissue needs to be taken into consideration when aiming for successful treatment of DFI. However, the vast majority of presently available pharmacokinetic data regarding bone tissues focuses on tissue homogenates, which provide no
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Bone penetration of daptomycin in diabetic patients with bacterial foot infections
2019, International Journal of Infectious DiseasesCitation Excerpt :If considering S. aureus, an intravenous dose of 6 mg/kg allowed bone IQs to always be >4 and often >10 at MIC equivalent to the MIC90 of this species (Gallon et al., 2009; Jones et al., 2017). By comparison, bone IQs for vancomycin, teicoplanin, and linezolid at their respective MIC50 for S. aureus ranged from 0.85 to 3.7, 0.6 to 2.4, and 7.55, respectively (Ziglam and Finch, 2001; Draghi et al., 2005; Garazzino et al., 2008; Traunmüller et al., 2010b). Bone daptomycin IQs remain positive up to a MIC of 1 mg/l, which is the current EUCAST clinical breakpoint for S. aureus and CoNS (EUCAST, 2019).
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Data from this study will be presented as an abstract and poster at the 4th Austrian Conference on Infectious Diseases, 5–8 May 2010, Saalfelden, Austria.
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These authors contributed equally to this work.