Bone penetration of daptomycin in diabetic patients with bacterial foot infections

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 0.25-4 mg/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 4.5 mg/l to 39.9 mg/l and from 31.8 mg/l to 110.9 mg/ l, respectively. Bone daptomycin concentrations at the moment of surgery varied from 1.2 mg/l to 17 mg/l. Up to a MIC of 1 mg/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 6 mg/kg, bone concentrations are likely to be effective against staphylococcal infections and infections due to low-MIC Enterococcus.

Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant

“…Similarly, although the efficacy of daptomycin against MRSE has been analyzed in several experimental studies, including endocarditis, tissue cage, and biofilm-associated catheter infection, little is known about its potential in bone-related infections. In our model, daptomycin alone showed a bacterial reduction of 3 log 10 CFU, and these data are consistent with the good penetration of daptomycin into bone tissue, even in diabetic patients (24). However, the bactericidal activity of daptomycin in our model was slower than the one observed in animals receiving linezolid or ceftaroline alone.…”

Modification of the Polymer of a Bone Cement with Biodegradable Microspheres of PLGA and Loading with Daptomycin and Vancomycin Improve the Response to Bone Tissue Infection

“…Unlike the bone treated with the formulations loaded with linezolid, the bone treated with daptomycin had a well-preserved structure, and the macrophages showed a wide dispersion throughout the bone tissue, helping to reduce the presence of bacteria. This behavior may be explained by the lipid nature of daptomycin, which, as has been proven in recent studies, facilitates tissue penetration [ 26 , 27 ], in contrast to vancomycin, which exerts its action more locally because it has greater difficulty diffusing through bone tissue [ 28 ].…”

“…In contrast, in the presence of daptomycin, macrophages were dispersed throughout all tissues studied, including bone marrow and trabecular bone. This observation could be explained by the greater ease with which daptomycin penetrates tissues, given its lipophilic nature, allowing it to achieve greater bacterial control [ 26 ]. This reasoning could explain the good results obtained by the Palacos R + PLGA cement + daptomycin group, in which the two mechanisms of antibacterial action described complemented each other [ 11 ].…”

Antibiotics in Necrotizing Soft Tissue Infections

“…Others found no impact of ischemia on diffusion of metronidazole [102]. In diabetic foot infection, a condition known to be associated with altered local perfusion, lipophilic molecules such as daptomycin, linezolid, and trimethoprim-sulfamethoxazole have shown good tissue penetration [95][96][97][98], while it was altered for hydrophilic molecules such as vancomycin [103]. While ceftazidime penetration was not affected by diabetes, it highly depended on tissue perfusion in another work [101], and employing high doses is suggested for cefepime [100].…”