Dataset Information

Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study.

ABSTRACT:

Introduction

In treatment of prosthetic vascular graft infection (PVGI), appropriate antimicrobial treatment is crucial for controlling the septic process and preventing re-infection of the new graft. Glycopeptides are the mainstay of treatment for device-related infections by methicillin-resistant Staphylococcus aureus strains, but with some limitations, especially concerning vancomycin-intermediate and glycopeptide-intermediate S. aureus. We report our experience using a high dose of daptomycin (DAP) for treatment of PVGI.

Methods

We reviewed medical reports of 26 patients treated with high doses of DAP (>8 mg/kg) and beta-lactams/aminosides for PVGI, defined as positive bacterial culture of intraoperative specimens or blood samples and/or clinical, biological, and radiological signs of infection. Clinical success was defined by resolution of all clinical signs at the end of follow-up, without the need for additional antibiotic therapy, and/or negative culture in case of new surgery.

Results

Cultures of intraoperative samples were positive in 21 patients (80.8%). Blood and intraoperative cultures were concomitantly positive in 10 patients. The main microorganism identified in microbiological samples was S. aureus (n = 18). Surgery was performed in 23 patients (88.4%). The mean duration of the DAP regimen was 12.3 ± 11.9 days. DAP was discontinued in 26 patients [need to switch to microbiological results (n = 19), bacterial pneumonia (n = 2), and increased creatine phosphokinase levels (n = 4)]. One patient had myalgia, while 9 received concomitant statins.

Conclusion

High-dose DAP therapy shows a satisfactory toxicity profile even in severely ill patients with multiple comorbidities, and may favorably compete with vancomycin, especially concerning the risk of induced nephrotoxicity.

SUBMITTER: Legout L

PROVIDER: S-EPMC4269615 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study.

Legout Laurence L D'Elia Piervito P Sarraz-Bournet Beatrice B Ettahar Nicolas N Haulon Stephan S Leroy Olivier O Senneville Eric E

Infectious diseases and therapy 20140904 2

<h4>Introduction</h4>In treatment of prosthetic vascular graft infection (PVGI), appropriate antimicrobial treatment is crucial for controlling the septic process and preventing re-infection of the new graft. Glycopeptides are the mainstay of treatment for device-related infections by methicillin-resistant Staphylococcus aureus strains, but with some limitations, especially concerning vancomycin-intermediate and glycopeptide-intermediate S. aureus. We report our experience using a high dose of d ...[more]

PMID: 25186318

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Project description:ObjectivesThe success of prosthetic vascular grafts in the management of peripheral arterial disease is frequently limited by the development of anastomotic neointimal hyperplasia (ANIH), with the host response to prosthetic grafts beginning soon after implantation. To address this, we combine a platform of polyethylene terephthalate (PET) fabric with an applied cryogel layer containing biologic agents to create a bioactive prosthetic graft system, with the ability to deliver therapeutics targeting modulators of the ANIH-associated transcriptome response, along with antithrombotic agents.MethodsHybrid graft materials were synthesized by cryopolymerization of methacrylated alginate and heparin onto electrospun (ePET), knitted PET (kPET), or woven PET (wPET). Arg-Gly-Asp (RGD) peptides were added to increase cell adhesion. Scanning electron microscopy (SEM) was used to study the microstructure at 1 day, and 2, 4, and 8 weeks. Physical properties such as swelling ratio, pore connectivity, shape recovery, and stiffness were evaluated. Human aortic endothelial cell (HAoEC) adherence was visualized using confocal microscopy after 24 hours and proliferation was evaluated with a resazurin-based assay for 7 days. Confocal microscopy was used to assess delivery of adeno-associated virus (AAV-GFP) after incubation of hybrid grafts with HAoECs. Heparin activity of the materials was measured using an anti-Xa assay.ResultsSEM demonstrated large interconnected pores throughout the entire structure for all graft types, with minimal degradation of the cryogel after 8 weeks. Hybrid materials showed a trend towards increased shape recovery, increased stiffness, decreased swelling ratio, and no difference in pore connectivity. HAoECs incorporated, adhered, and proliferated over 7 days on all materials. HAoECs were successfully transduced with AAV-GFP from the hybrid graft materials. Anti-Xa assay confirmed continued activity of heparin from all materials for over 7 days.ConclusionsWe have developed a bioactive prosthetic graft system with a cryogel coating capable of delivering biologic agents with antithrombotic activity. By applying the cryogel and selected agents onto PET prior to graft implantation, this study sets the stage for the system to be individualized and tailored to the patient, with bioengineering and targeted gene therapy strategies dovetailing to create an improved prosthetic graft adaptable to emerging knowledge and technologies.

Project description:BackgroundPrevious studies of both clinically-derived and in vitro passage-derived daptomycin-resistant (DAP-R) Staphylococcus aureus strains demonstrated the coincident emergence of increased DAP MICs and resistance to host defense cationic peptides (HDP-R).MethodsIn the present investigation, we studied a parental DAP-susceptible (DAP-S) methicillin-resistant Staphylococcus aureus (MRSA) strain and three isogenic variants with increased DAP MICs which were isolated from both DAP-treated and DAP-untreated rabbits with prosthetic joint infections. These strains were compared for: in vitro susceptibility to distinct HDPs differing in size, structure, and origin; i.e.; thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide-1 [hNP-1]; cell membrane (CM) phospholipid and fatty acid content; CM order; envelope surface charge; cell wall thickness; and mprF single nucleotide polymorphisms (SNPs) and expression profiles.ResultsIn comparison with the parental strain, both DAP-exposed and DAP-naive strains exhibited: (i) significantly reduced susceptibility to each HDP (P<0.05); (ii) thicker cell walls (P<0.05); (iii) increased synthesis of CM lysyl-phosphatidylglycerol (L-PG); (iv) reduced content of CM phosphatidylglycerol (PG); and (v) SNPs within the mprF locus No significant differences were observed between parental or variant strains in outer CM content of L-PG, CM fluidity, CM fatty acid contents, surface charge, mprF expression profiles or MprF protein content. An isolate which underwent identical in vivo passage, but without evolving increased DAP MICs, retained parental phenotypes and genotype.ConclusionsTHESE RESULTS SUGGEST: i) DAP MIC increases may occur in the absence of DAP exposures in vivo and may be triggered by organism exposure to endogenous HDPs: and ii) gain-in-function SNPs in mprF may contribute to such HDP-DAP cross-resistance phenotypes, although the mechanism of this relationship remains to be defined.

Dataset Information

Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study.

Introduction

Methods

Results

Conclusion

Publications

Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study.

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