Amphotericin risk factors

Amphotericin B-induced ARF occurs in as many as 40% to 65% of patients treated with the conventional desoxycholate formulation.30 Nephrotoxicity is due to renal arterial vasoconstriction and distal renal tubule cell damage. Risk factors include high doses, treatment for at least 7 days, preexisting kidney dysfunction, and concomitant use of other nephrotoxic drugs.31 Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease the incidence of ARF amphotericin B lipid complex, amphotericin colloidal dispersion, and liposomal amphotericin B. The range of... 

Response to antifungal therapy in invasive candidiasis is often more rapid than for endemic fungal infections. Resolution of fever and sterilization of blood cultures are indications of response to antifungal therapy. Toxicity associated with antifungal therapy is similar in these patients as described earlier with the caveat that some toxicities maybe more pronounced in crit-ically-ill patients with invasive candidiasis. Nephrotoxicity and electrolyte disturbances, with amphotericin B in particular, are problematic and may not be avoidable even with lipid amphotericin B formulations. Fluconazole and echinocandins are generally safer options, and are generally well tolerated. Decisions to use one class of agents over the other is principally driven by concerns of non-albicans species, patient tolerability, or history of prior fluconazole exposure (risk factor for non-albicans species.). 

Solid-organ transplantation Liver transplantation Micafungin 50 mg (1 mg/kg in patients under 50 kg) IV daily Patients with two or more key risk factor Amphotericin B IV 10-20 mg daily or Liposomal amphotericin B (AmBisome) 1 mg/kg/day or flucona-... 

Gomez E, Sutton SS, Olyaei A, et al. 2001. Multicenter evaluation of risk factors for aspergillosis in patients treated with lipoid amphotericin B products Outcomes, utilization parameters, and benchmarking. Am J Healtb-Syst Pbarm 36 2. 

Fisher MA, Talbot GH, Maislin G, McKeon BP, Tynan KP, Strom BL. Risk factors for amphotericin B-... 

Euber AD, Maa E, Earn M, Guglielmo BJ. Risk factors for amphotericin B-induced nephrotoxicity. J Antimicrob Chemother 1999 43 267-71. 

Girmenia C, Cimino G, Micozzi A, et al. Risk Factors For Nephrotoxicity Associated With Conventional Amphotericin BTherapy. The American Journal of Medicine 2002 113 351. 

Risk factors include baseline renal insufficiency, higher average daily doses, diuretic use, volume depletion, and concomitant administration of other nephrotoxins (cyclosporine in particular). Rapid infusions of amphotericin B have the potential to increase toxicity. A recent comparison of 24-hour continuous infusions with conventional 4-hour infusions revealed a significant reduction of toxicity, attributed to decreased pretubular effects (e.g., effects on renal blood flow and GFR). ... 

Few data are available for assessing the role of fluconazole as empirical therapy for suspected fungemia or for isolates other than C. albicans. Because fluconazole has poor activity against Aspergillus spp. and some non-albicans strains of Candida, many clinicians advocate amphotericin B as the therapy of choice in patients with suspected fungemia. If therapy is given, its use should be limited to patients with (1) Candida colonization at multiple sites, (2) multiple other risk factors, and (3) the absence of any other uncorrected causes of fever. " ... 

A study assessing the risk factors for nephrotoxicity with aminoglycosides (tobramycin and gentamicin) enrolled 1489 patients, 157 of whom developed clinical nephrotoxicity. Of these patients 118 had no immediately identifiable cause (sueh as acute renal failure) and further evaluation of other risk factors found that the concurrent use of amphotericin B significantly increased the risk of nephrotoxicity. ... 

Nephrotoxicity associated with amphotericin B administration in humans is dose related and it may be severe and result in acute renal failure. The incidence of acute renal failure may be as high as 49 to 65%. It is accompanied by an increase in serum creatinine. Mortality may be high and is increased by the co-administration of other nephrotoxic drugs. Risk factors include cumulative dose, abnormal baseline renal function, concomitant nephrotoxic drugs such as cyclosporin, and infusion rates. However, rapid infusion rates are also associated with severe hyperkalaemia and potentially fatal arrhythmias. " In one case, a woman given 5mg/kgbw/day amphotericin B instead of the... 

P. C. Craven and D. H. Gremillion, Risk factors of ventricular fibrillation during rapid amphotericin B infusion, Antimicrob. Agents Chemother., 1985, 27, 868-871. 

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