Towards a definition of daptomycin optimal dose: Lessons learned from experimental and clinical data

Senneville, Éric; Caillon, Jocelyne; Calvet, Brigitte; Jehl, F.

doi:10.1016/j.ijantimicag.2015.11.005

Cited by 28 publications

(17 citation statements)

References 81 publications

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“…Therefore, the dosage regimen of 6 mg/kg allowed bone daptomycin concentrations that could be effective against Staphylococcus infections and at least equivalent to other drugs classically used for this indication. Besides, as many studies have shown that daptomycin can be used safely at higher dosages of up to 12 mg/kg, daptomycin seems to be of particular interest for the treatment of staphylococcal DFI (Senneville et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In a pooled analysis of the two large real-world registries, CORE in the USA and EU-CORE in Europe, daptomycin usage was analysed in 11 557 patients, of whom 8.6% were treated for osteomyelitis, with or without material, with an estimated clinical success rate of 77.7%. The promising role of daptomycin in such infections has been strengthened by the ability to use higher dosages of this molecule, up to 12 mg/kg, but also by in vitro studies showing its ability to penetrate bone tissue (Malizos et al, 2016;Seaton et al, 2016;Senneville et al, 2016). Traunmüller et al provided the first in vitro data regarding daptomycin bone penetration in 2010.…”

Section: Introductionmentioning

confidence: 99%

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Bone penetration of daptomycin in diabetic patients with bacterial foot infections

Grillon

Gaudias²,

Ronde-Ousteau³

et al. 2019

International Journal of Infectious Diseases

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bone penetration of daptomycin in diabetic patients with bacterial foot infections

Grillon

Gaudias²,

Ronde-Ousteau³

et al. 2019

International Journal of Infectious Diseases

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“…Also, free DAP Cmax values usually fell into the MSW when using lower dosages, suggesting a risk of in vivo selection of resistant mutants, especially at sites of infection where the concentration of DAP is low. Therefore, high daily doses of DAP (≥10 mg/kg) may be considered for the treatment of infections due to E. faecium, as recently recommended for severe and deep-seated enterococcal infections [6]. Finally, the reliability of MPC as a predictor of the emergence of DAP resistance must be further confirmed.…”

Section: Resultsmentioning

confidence: 99%

“…Whereas doses of 4 mg/kg and 6 mg/kg are approved by the US Food and Drug Administration (FDA), numerous in vitro and animal data suggest that higher doses (up to 12 mg/kg) may improve DAP bactericidal activity and reduce the risk of emergence of resistance whilst drug tolerance is well conserved [3,6]. Although the development of DAP resistance has so far remained uncommon in enterococci (spontaneous in vitro resistance frequencies of ca.…”

Section: Introductionmentioning

confidence: 99%

Mutant prevention concentrations of daptomycin for Enterococcus faecium clinical isolates

Sinel

Jaussaud

Auzou

et al. 2016

International Journal of Antimicrobial Agents

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“…) particularly with monotherapy, and optimal dosing regimes are still being investigated (Senneville et al . ).…”

Section: Introductionmentioning

confidence: 97%

Anin vitrobiofilm model ofStaphylococcus aureusinfection of bone

Sweeney

Lovering

Bowker

et al. 2019

Lett Appl Microbiol

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Significance and Impact of the Study: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an in vitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis. AbstractChronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an in vitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24 h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72 h biofilms with gentamicin and daptomycin for 24 h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100 mg l À1 gentamicin and 1000 mg l À1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7 days resulted in ≥3 log reductions in cell numbers by 48 h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7 days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone.

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Towards a definition of daptomycin optimal dose: Lessons learned from experimental and clinical data

Cited by 28 publications

References 81 publications

Bone penetration of daptomycin in diabetic patients with bacterial foot infections

Bone penetration of daptomycin in diabetic patients with bacterial foot infections

Mutant prevention concentrations of daptomycin for Enterococcus faecium clinical isolates

Anin vitrobiofilm model ofStaphylococcus aureusinfection of bone

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