Antoine Grillon1, Xavier Argemi2, Jeannot Gaudias3, Cécile Ronde-Ousteau3, Cyril Boeri3, Jean-Yves Jenny3, Yves Hansmann2, Nicolas Lefebvre4, François Jehl5. 1. Hôpitaux Universitaires, Institut de Bactériologie, Strasbourg, France; Virulence Bactérienne Précoce, Université de Strasbourg, CHRU de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg France. Electronic address: antoine.grillon@chru-strasbourg.fr. 2. Virulence Bactérienne Précoce, Université de Strasbourg, CHRU de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg France; Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France. 3. Hôpitaux Universitaires, Centre de Chirurgie Orthopédique et de la Main (CCOM), Strasbourg, France. 4. Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France. 5. Hôpitaux Universitaires, Institut de Bactériologie, Strasbourg, France.
Abstract
OBJECTIVES: Daptomycin has shown clinical efficacy in diabetic foot infections (DFI). However, only limited data are available on its bone penetration in this particular population. The aim of this study was to determine daptomycin bone concentrations in patients with DFI undergoing surgery after multiple daptomycin infusions and to determine bone daptomycin inhibitory quotients (IQs) for the predominant gram-positive species involved in DFI. METHODS: Fourteen adult patients hospitalized with DFI treated with daptomycin and requiring surgical bone debridement and amputation were included in this single-centre prospective study. Daptomycin concentrations in serum and bone were determined by HPLC at steady state. Bone IQs were then calculated according to different minimum inhibitory concentrations (MICs; range 0.25-4mg/l) that are representative of the main MICs for Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and Enterococcus sp populations. RESULTS: Residual and peak concentrations varied from 4.5mg/l to 39.9mg/l and from 31.8mg/l to 110.9mg/l, respectively. Bone daptomycin concentrations at the moment of surgery varied from 1.2mg/l to 17mg/l. Up to a MIC of 1mg/l, which is the epidemiological cut-off value (ECOFF) and breakpoint value for S. aureus and CoNS, all bone daptomycin IQs were positive. The highest bone IQs were observed with Staphylococcus species. Calculated bone IQs for Enterococcus species were often weak at MIC values near the ECOFF. CONCLUSIONS: Daptomycin penetrates bone well in patients treated for DFI. At an initially recommended dosage of 6mg/kg, bone concentrations are likely to be effective against staphylococcal infections and infections due to low-MIC Enterococcus.
OBJECTIVES:Daptomycin has shown clinical efficacy in diabetic foot infections (DFI). However, only limited data are available on its bone penetration in this particular population. The aim of this study was to determine daptomycin bone concentrations in patients with DFI undergoing surgery after multiple daptomycin infusions and to determine bone daptomycin inhibitory quotients (IQs) for the predominant gram-positive species involved in DFI. METHODS: Fourteen adult patients hospitalized with DFI treated with daptomycin and requiring surgical bone debridement and amputation were included in this single-centre prospective study. Daptomycin concentrations in serum and bone were determined by HPLC at steady state. Bone IQs were then calculated according to different minimum inhibitory concentrations (MICs; range 0.25-4mg/l) that are representative of the main MICs for Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and Enterococcus sp populations. RESULTS: Residual and peak concentrations varied from 4.5mg/l to 39.9mg/l and from 31.8mg/l to 110.9mg/l, respectively. Bone daptomycin concentrations at the moment of surgery varied from 1.2mg/l to 17mg/l. Up to a MIC of 1mg/l, which is the epidemiological cut-off value (ECOFF) and breakpoint value for S. aureus and CoNS, all bone daptomycin IQs were positive. The highest bone IQs were observed with Staphylococcus species. Calculated bone IQs for Enterococcus species were often weak at MIC values near the ECOFF. CONCLUSIONS:Daptomycin penetrates bone well in patients treated for DFI. At an initially recommended dosage of 6mg/kg, bone concentrations are likely to be effective against staphylococcal infections and infections due to low-MIC Enterococcus.
Authors: S Albac; D Labrousse; D Hayez; N Anzala; D Bonnot; P Chavanet; E Aslangul; D Croisier Journal: Antimicrob Agents Chemother Date: 2020-01-27 Impact factor: 5.191
Authors: Joaquin García-García; Galo Azuara; Oscar Fraile-Martinez; Cielo García-Montero; Miguel Angel Álvarez-Mon; Sara Ruíz-Díez; Melchor Álvarez-Mon; Julia Buján; Natalio García-Honduvilla; Miguel A Ortega; Basilio De la Torre Journal: Polymers (Basel) Date: 2022-02-23 Impact factor: 4.329