Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement

Montange, Damien; Berthier, Francis; Leclerc, Grégoire; Serre, A; Jeunet, L.; Bérard, Michel; Muret, Patrice; Vettoretti, Lucie; Leroy, J.; Hoën, Bruno; Chirouze, Catherine

doi:10.1128/aac.02344-14

Cited by 49 publications

(33 citation statements)

References 30 publications

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“…The study results showed that despite the low vascularity associated with DFI, daptomycin penetrates bone well in patients treated for this infection and reached a sufficient concentration in the bone. The residual and peak concentrations were found to be somewhat equivalent to those observed in other studies in this particular population, making the daptomycin bone concentrations relevant (Traunmüller et al, 2010a;Montange et al, 2014).…”

Section: Discussionsupporting

confidence: 76%

“…The authors showed that the bone/plasma area under the curve (AUC) of daptomycin concentration was 1.08 in patients with DFI and osteomyelitis, after four to five injections of a 6 mg/kg daptomycin regimen. In a second study conducted by Montange et al in 2014, daptomycin bone penetration reached a much lower level (Montange et al, 2014). The authors studied daptomycin bone concentrations after a single intravenous dose infusion of 8 mg/kg in patients undergoing knee or hip replacement.…”

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: Discussionsupporting

confidence: 76%

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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“…Antimicrobials such as vancomycin may not penetrate bone tissue well (17,18), yet they are often used to treat osteomyelitis (4). It has been suggested that daptomycin has bone penetration (19). We found levels of exebacase in bone to be ϳ15% of plasma levels after a single dose of 10 mg/kg.…”

mentioning

confidence: 77%

Exebacase in Addition to Daptomycin Is More Active than Daptomycin or Exebacase Alone in Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

Karau

Schmidt-Malan

Yan

et al. 2019

Antimicrob Agents Chemother

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Bacteriophage-derived lysins are being developed as anti-infective agents. In an acute osteomyelitis methicillin-resistant Staphylococcus aureus (MRSA) model, rats receiving no treatment or treatment with daptomycin, exebacase (CF-301), or daptomycin plus exebacase had means of 5.13, 4.09, 4.65, and 3.57 log 10 CFU/gram of bone, respectively. All treated animals had fewer bacteria than did untreated animals (P Յ 0.0001), with daptomycin plus exebacase being more active than daptomycin (P ϭ 0.0042) or exebacase (P Ͻ 0.001) alone.

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“…Montange et al reported mean daptomycin bone penetration rate of 14.1 AE11.9% in 16 arthroplasty patients after 8 mg/kg dose with mean concentrations of 36.3 AE 2.9, 6.5 AE 3.6, and 21.6 AE 6.8 mg/mL in shinbone, thighbone, and synovial fluid, respectively (Montange et al, 2014). In another study, when 4-5 doses of 6 mg/kg/day of daptomycin were given to 9 patients with diabetic foot infection, mean C max in metatarsal bone was 4.7 mg/ mL (Traunmuller et al, 2010).…”

Section: Daptomycinmentioning

confidence: 99%

Antibiotic penetration into bone and joints: An updated review

Thabit

Fatani

Bamakhrama

et al. 2019

International Journal of Infectious Diseases

223

155

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A B S T R A C TTreatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC 90 and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.

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Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement

Cited by 49 publications

References 30 publications

Bone penetration of daptomycin in diabetic patients with bacterial foot infections

Bone penetration of daptomycin in diabetic patients with bacterial foot infections

Exebacase in Addition to Daptomycin Is More Active than Daptomycin or Exebacase Alone in Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

Antibiotic penetration into bone and joints: An updated review

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