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- Martial, Lisa C, et al.
(author)
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Dose Reduction of Caspofungin in Intensive Care Unit Patients with Child Pugh B Will Result in Suboptimal Exposure.
- 2016
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In: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 55:6, s. 723-733
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Caspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokinetic target attainment for various dosing strategies.METHODS: Caspofungin pharmacokinetic data from 21 intensive care unit (ICU) patients was available. A population pharmacokinetic model was developed. Various dosing regimens (loading dose/maintenance dose) were simulated: licensed regimens (I) 70/50 mg (for BW <80 kg) or 70/70 mg (for BW >80 kg); and (II) 70/35 mg (for Child-Pugh score B); and adapted regimens (III) 100/50 mg (for Child-Pugh score B); (IV) 100/70 mg; and (V) 100/100 mg. Target attainment based on a preclinical pharmacokinetic target for Candida albicans was assessed for relevant minimal inhibitory concentrations (MICs).RESULTS: A two-compartment model best fitted the data. Clearance was 0.55 L/h and the apparent volumes of distribution in the central and peripheral compartments were 8.9 and 5.0 L, respectively. The median area under the plasma concentration-time curve from time zero to 24 h on day 14 for regimens I-V were 105, 65, 93, 130, and 186 mg·h/L, respectively. Pharmacokinetic target attainment was 100 % (MIC 0.03 µg/mL) irrespective of dosing regimen but decreased to (I) 47 %, (II) 14 %, (III) 36 %, (IV) 69 %, and (V) 94 % for MIC 0.125 µg/mL.CONCLUSION: The caspofungin maintenance dose should not be reduced in non-cirrhotic ICU patients based on the Child-Pugh score if this classification is driven by hypoalbuminemia as it results in significantly lower exposure. A higher maintenance dose of 70 mg in ICU patients results in target attainment of >90 % of the ICU patients with species with an MIC of up to 0.125 µg/mL.
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- Brüggemann, Holger, et al.
(author)
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Staphylococcus saccharolyticus Isolated From Blood Cultures and Prosthetic Joint Infections Exhibits Excessive Genome Decay
- 2019
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 10
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Journal article (peer-reviewed)abstract
- The slow-growing, anaerobic, coagulase-negative species Staphylococcus saccharolyticus is found on human skin and in clinical specimens but its pathogenic potential is unclear. Here, we investigated clinical isolates and sequenced the genomes of seven strains of S. saccharolyticus. Phylogenomic analyses showed that the closest relative of S. saccharolyticus is Staphylococcus capitis with an average nucleotide identity of 80%. Previously sequenced strains assigned to S. saccharoiyticus are misclassified and belong to S. capitis. Based on single nucleotide polymorphisms of the core genome, the population of S. saccharolyticus can be divided into two clades that also differ in a few larger genomic islands as part of the flexible genome. An unexpected feature of S. saccharolyticus is extensive genome decay, with over 300 pseudogenes, indicating ongoing reductive evolution. Many genes of the core metabolism are not functional, rendering the species auxotrophic for several amino acids, which could explain its slow growth and need for fastidious growth conditions. Secreted proteins of S. saccharolyticus were determined; they include stress response proteins such as heat and oxidative stress-related factors, as well as immunodominant staphylococcal surface antigens and enzymes that can degrade host tissue components. The strains secrete lipases and a hyaluronic acid lyase. Hyaluronidase as well as urease activities were detected in biochemical assays, with Glade-specific differences. Our study revealed that S. saccharolyticus has adapted its genome, possibly due to a recent change of habitat; moreover, the data imply that the species has tissue-invasive potential and might cause prosthetic joint infections.
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- Jägervall, C. D., et al.
(author)
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Patients’ experiences of orgasm changes and loss of ejaculation after radical prostatectomy
- 2016
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In: Läkartidningen. - 0023-7205. ; 113:36-37
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Journal article (peer-reviewed)abstract
- In this study we report on men’s experiences of orgasm changes and loss of ejaculation after radical prostatectomy. Ten men, all recruited through a Swedish hospital, were interviewed and data was analyzed using qualitative content analysis. The results showed that the experience of orgasm has weakened but that the loss of ejaculation was not perceived as a loss per se. However, the risk of urine release during orgasm was troublesome and inhibiting. These challenges were framed within an existential narrative about sexuality, as expressed in preoperative sexual farewell rituals and postoperative feelings of ambivalence and regret. These findings can be used in the design of patient information and for sexual rehabilitation treatment. © 2016, Swedish Medical Association. All rights reserved.
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