FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2034302588> ?p ?o ?g. }

• W2034302588 endingPage "849" @default.
• W2034302588 startingPage "847" @default.
• W2034302588 abstract "The comments by Dr Mehta concerning our review include some erroneous information and he appears to have misinterpreted, misquoted or invented parts of our review of the treatment of fungal infections, compiled in 1997 and published in March 1998 (6). We welcome the opportunity to reply. His thesis appears to be that cost considerations should encourage the use of Abelcet on the grounds that there are no data to suggest lower doses of AmBisome, which would be cost-comparable, are as effective as Abelcet in the treatment of confirmed fungal infections. We do not agree with this. The first and most obvious error in Dr Mehta's letter is his claim that the licensed dose for AmBisome in the U.K. is 3–5 mg/kg. The data sheet actually states: ‘Therapy for systemic and/or deep mycoses is usually instituted at a daily dose of 1.0 mg/kg of body weight, and increased stepwise to 3.0 mg/kg, as required.’ This recommendation was based on the key studies to which Dr Mehta refers. In 5) the median dose of AmBisome administered was 1684 mg for a median of 12 d. This equates to almost exactly 2 mg/kg/d for an average 70 kg patient. 7) quoted a median daily dose for proven and presumed invasive mycoses of 2.4 mg/kg in their series. The 3 mg/kg/d dose that Dr Mehta suggests for these studies is therefore incorrect. 7) specifically included in their Materials and Methods section the statement: ‘Dosing was begun at 0.5 or 1.0 mg/kg, and the dose was then increased in a step-wise fashion.’ Dr Mehta then proceeds to mention the work of 3) and suggests that the response rate of patients with proven invasive aspergillosis (IA) to AmBisome at 4 mg/kg/d appeared to be better than 1 mg/kg/d. We did not quote that paper because it was published after our review, but we would suggest that the results are very equivocal. On the one hand, the overall clinical response in both probable and proven IA was encouraging at both dose levels: 26/41 (64%) in the 1 mg/kg arm and 22/46 (48%) in the 4 mg/kg arm. The radiological response rates were very similar. The response rates in the 20 patients with proven IA were also encouraging, at 38% in the 1 mg/kg cohort and 58% in the 4 mg/kg cohort. On the other hand, there was a trend towards a better outcome among proven cases of IA in the higher dose group, compounded by generally a worse prognosis among the patients in that dose group. One might therefore conclude that 1 mg/kg of AmBisome is an effective dose in IA but 4 mg/kg could be better, though the evidence was not definitive. The response rates in 3) are in line with other reported efficacy rates for AmBisome and are comparable with the 55/130 responses (42%) reported for Abelcet at 5 mg/kg by 8) in their study. As with 3), we did not cover the papers from 9, 8) because they had not been published at the time of our review was prepared. Dr Mehta moves on to make the alarming accusation that our ‘recommendation of 1–3 mg/kg of AmBisome in invasive aspergillosis has no factual basis and must be considered somewhat irresponsible.’ This we refute totally. What we actually said was: ‘It is usual to begin treatment with AmBisome with a dose of 1.0–3.0 mg/kg, or even higher’, which is a statement of fact and in no way irresponsible. Again, we have been grossly misquoted. What Dr Mehta has highlighted is that there is some considerable debate about the most appropriate dosing of AmBisome, whilst there is much less known about Abelcet. The reason is simple. There are very little reliable data regarding Abelcet at doses below 5 mg/kg and the tolerance of the agent above 5 mg/kg is extremely poor. This gives clinicians little option. AmBisome, however, is very different. As indicated, there exists good clinical data, corroborated by preclinical data, that doses from 1 mg/kg/d are effective in the treatment of mycoses. Several reports have been published of the use of AmBisome up to 15 mg/kg/d. This tends to suggest that the available dose range for AmBisome is very wide indeed and has led to different authors suggesting different options, based on their own experience and guidance from the literature. Far from being a criticism of AmBisome, this can only be seen as one of the product's strengths. Dr Mehta is incorrect to say that the study of 1), which has not been published in a peer-reviewed journal and therefore not easily reviewed in detail, is the only prospective randomized study to have compared any lipid formulation of amphotericin with the conventional drug in patients with a proven fungal infection. A recent randomized comparison of AmBisome at 5 mg/kg/d with conventional amphotericin B at 1 mg/kg/d in the treatment of IA (4) suggested that AmBisome was significantly better in terms of response at day 14 and overall mortality, adjusted for malignancy status. Even at this high dose, the safety profile of AmBisome, in terms of nephrotoxicity, was superior to that of the conventional drug. We thank Dr Mehta for bringing the 10) report to our attention, which certainly adds to our understanding of Abelcet and its use. Dr Mehta's acceptance and understanding of the tissue distribution of AmBisome and Abelcet is also of concern. The pathogenesis of invasive fungal infection and pharmacokinetics of lipid formulations of amphotericin B in experimental models are very different from that seen in humans. Moreover, an independent review of the 7) paper, concerning tissue levels in three patients, not one, makes a very definite statement: ‘Substantial amounts of drug [AmBisome] were recovered in kidney and lung tissue’ (2). These levels were far high than the minimum inhibitory concentration against all fungal pathogens. We thank Dr Mehta for giving us the opportunity to update and clarify his understanding of our review. It is hoped that our appraisal of the most recent literature outlined here in the context of his letter reinforce the recommendations that we made in the original review." @default.
• W2034302588 created "2016-06-24" @default.
• W2034302588 creator A5078041825 @default.
• W2034302588 creator A5080844820 @default.
• W2034302588 date "1999-06-01" @default.
• W2034302588 modified "2023-10-18" @default.
• W2034302588 title "Lipid preparations of amphotericin for the treatment of fungal infections" @default.
• W2034302588 cites W1525050661 @default.
• W2034302588 cites W2037064781 @default.
• W2034302588 cites W2061857343 @default.
• W2034302588 cites W2068851856 @default.
• W2034302588 cites W2119390272 @default.
• W2034302588 cites W2129948097 @default.
• W2034302588 cites W2144030592 @default.
• W2034302588 cites W2163206122 @default.
• W2034302588 cites W2328084459 @default.
• W2034302588 doi "https://doi.org/10.1046/j.1365-2141.1999.1498a.x" @default.
• W2034302588 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10354163" @default.
• W2034302588 hasPublicationYear "1999" @default.
• W2034302588 type Work @default.
• W2034302588 sameAs 2034302588 @default.
• W2034302588 citedByCount "0" @default.
• W2034302588 crossrefType "journal-article" @default.
• W2034302588 hasAuthorship W2034302588A5078041825 @default.
• W2034302588 hasAuthorship W2034302588A5080844820 @default.
• W2034302588 hasConcept C16005928 @default.
• W2034302588 hasConcept C177713679 @default.
• W2034302588 hasConcept C2779548794 @default.
• W2034302588 hasConcept C2779629538 @default.
• W2034302588 hasConcept C71924100 @default.
• W2034302588 hasConcept C86803240 @default.
• W2034302588 hasConcept C89423630 @default.
• W2034302588 hasConcept C98274493 @default.
• W2034302588 hasConceptScore W2034302588C16005928 @default.
• W2034302588 hasConceptScore W2034302588C177713679 @default.
• W2034302588 hasConceptScore W2034302588C2779548794 @default.
• W2034302588 hasConceptScore W2034302588C2779629538 @default.
• W2034302588 hasConceptScore W2034302588C71924100 @default.
• W2034302588 hasConceptScore W2034302588C86803240 @default.
• W2034302588 hasConceptScore W2034302588C89423630 @default.
• W2034302588 hasConceptScore W2034302588C98274493 @default.
• W2034302588 hasIssue "3" @default.
• W2034302588 hasLocation W20343025881 @default.
• W2034302588 hasLocation W20343025882 @default.
• W2034302588 hasOpenAccess W2034302588 @default.
• W2034302588 hasPrimaryLocation W20343025881 @default.
• W2034302588 hasRelatedWork W1503565818 @default.
• W2034302588 hasRelatedWork W1969131286 @default.
• W2034302588 hasRelatedWork W1995422078 @default.
• W2034302588 hasRelatedWork W2117849932 @default.
• W2034302588 hasRelatedWork W2126301506 @default.
• W2034302588 hasRelatedWork W2155504441 @default.
• W2034302588 hasRelatedWork W2320448713 @default.
• W2034302588 hasRelatedWork W2346719327 @default.
• W2034302588 hasRelatedWork W4250313633 @default.
• W2034302588 hasRelatedWork W4252371801 @default.
• W2034302588 hasVolume "105" @default.
• W2034302588 isParatext "false" @default.
• W2034302588 isRetracted "false" @default.
• W2034302588 magId "2034302588" @default.
• W2034302588 workType "article" @default.