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PAPERS: Patrick Schöffski, Mathias Freund, R Wunder, D Petersen, C H Köhne, H Hecker, U Schubert, and A Ganser Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study BMJ 1998; 317: 379-384 [Abstract] [Full text]

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Janos Sinko   (27 November 1998)

Untitled 27 November 1998
Janos Sinko Send response to journal: Re: this article	EDITOR - Schöffski et al discourage the use of amphotericin B in intralipid1. Indeed much controversial facts were published in the past regarding its efficacy and toxicity. It can be feared that the present study also failed to clarify the role of the "liposomal ampho of the poor" in the treatment of pulmonary infiltrates and FUO in neutropenia. The trial - though randomised - was nonblinded. Number of the recruited subjects remained rather low due to premature closure. This combined with the obvious imbalance of pulmonary infiltrates and diuretic use between treatment groups (each remaining below level of significance) may greatly decrease statistical power. Duration of treatment and dosage seemed to be suboptimal, especially for cases of proven mycosis. Intermittent administration after day 8 and a further dose reduction in 10 patients does not allow to draw any conclusion regarding efficacy. It is not clear what the authors call significant renal impairment as mean creatinine levels rose by mean 10% above maximum normal level. We have administered amphotericin B with intralipid in a mean daily dose of 68 mg to 25 patients2. The cumulative doses by treatment and the total dose by patient reached mean 1,99 and 3,2 g, respectively. A reversible rise in serum creatinine by 16% was observed not requiring any intervention. Schöffski et al experienced pulmonary toxicity in the lipid arm. As they admit no relevant examinations were performed to clarify the mechanism of dyspnoea. Neither a bronchoalveolar lavage, nor ventilation-perfusion scans or any high resolution imaging were done. One might wonder whether autopsy could confirm any ultrastructural changes revealing lipid overload. Lacking any evidence of the role of drug incompatibility several other explanations might be possible. Most important is the speed administration being more than double allowed by the manufacturer3. A rapid infusion of plain lipid emulsion might have caused similar events but TNF-alpha mobilisation or even psychical stress also could play a role. Though rarely reported pulmonary toxicity of amphotericin B in intralipid cannot be excluded in certain settings. There would be a need for a well designed study to detect risk factors and mechanism of damage. However as long as manufacturers disregard the question by simply prohibiting the admixture of both amphotericin B and lipid emulsions no such large multicentric trial will ever be planned and truth about merits and drawbacks of this formulation will probably be never learned. János Sinkó Head Infectious Diseases Department of Hematology St.László Hospital, Gyáli u 5-7, Budapest 1097 Hungary 1. Schöffski P, Freund M, Wunder R, Petersen D, Köhne CH, Hecker H, Schubert U, Ganser A: Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study. BMJ 1998:317:379-84 (8 August) 2. Sinkó J, Prinz Gy, Nikolova R, Lueff S, Fekete S: Amphotericin B intralipid emulsion treatment in invasive fungal infections of neutropenic patients. Lege Artis Medicinae (Hungary, abstract in English) 1995:5:434- 8. 3. Kabi Pharmacia Sweden: Package insert to Intalipid 10% and 20% infusion.