amphotericin-b--deoxycholate-drug-combination and Hypokalemia

Amphotericin B deoxycholate (ABD) is the best therapeutic agent available for the treatment of most systemic fungal infections. However, some untoward adverse effects such as nephrotoxicity may limit its appropriate therapeutic use. We conducted a randomized, controlled trial ofthe infusion of fat emulsion (Intralipid) shortly after the infusion of ABD to evaluate its effects on reducing ABD-associated nephrotoxicity. Our patient population was made up of 31 patients who were randomized into two groups: an intervention group (n = 16) and a control group (15 patients). There were no statistically significant differences between the two groups in demographic or clinical variables. All patients received 1mg/kg/day of ABD in dextrose 5%. In addition, the patients in the intervention arm received Intralipid 10%, which was started as soon as possible within 1 hour after the infusion of ABD. ABD-associated nephrotoxicity was defined as a minimum 50% increase in baseline serum creatinine to a minimum of 2mg/dl. We also measured daily serum creatinine changes during the first 2 weeks of treatment, and we compared some other relevant indices of renal function, as well as ABD-related hypokalemia. We found no statistically significant differences between the two treatments in terms of ABD-associated nephrotoxicity or any of the other indices. We conclude that the administration of Intralipid 10% early after infusion of ABD in dextrose 5% does not have any effect in decreasing ABD-associated nephrotoxicity or hypokalemia.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Deoxycholic Acid; Drug Combinations; Fat Emulsions, Intravenous; Female; Head; Humans; Hypokalemia; Invasive Fungal Infections; Kidney; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Neck; Treatment Outcome; Young Adult

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.

Topics: Adult; Amphotericin B; Anemia; Antifungal Agents; Blood Cell Count; Coinfection; Creatinine; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Female; Flucytosine; Hemoglobins; HIV; HIV Infections; Humans; Hypokalemia; Induction Chemotherapy; Kidney; Male; Meningitis, Cryptococcal; Neutropenia; Survival Analysis; Treatment Outcome

Nephrotoxicity evaluations between liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) have provided mixed results. This retrospective study used an electronic medical record database of hospitalized patients with invasive fungal infections treated with either L-AMB or ABLC. Patients had renal insufficiency, clinical condition suggesting intolerance to amphotericin B deoxycholate (CAB), or recent CAB exposure. Baseline SCr, exposure to other nephrotoxic agents, and total amphotericin B exposure were similar between the groups. In 105 patients administered L-AMB, 10.6% had nephrotoxicity versus 22.6% of 222 patients administered ABLC (P = 0.020). A logistic regression model found ABLC patients had 3.48 higher odds (95% CI 1.05-11.52) than L-AMB of developing nephrotoxicity. Infusion reactions were more prevalent with ABLC (23.9% versus 9.5%, P = 0.002) as was hypomagnesemia (44.3% versus 28.1%, P = 0.033). This study demonstrated that L-AMB is associated with less nephrotoxicity, infusion reactions and hypomagnesemia than ABLC in patients at increased risk of nephrotoxicity.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Humans; Hypokalemia; Length of Stay; Male; Middle Aged; Multivariate Analysis; Mycoses; Renal Insufficiency; Retrospective Studies

Amphotericin B colloidal dispersion (ABCD) is a novel lipid formulation of amphotericin B designed to diminish toxic effects of the drug. In the following report, nine cases of suspected (n = 4) and proven (n = 5) deep Candida infection, treated sequentially with amphotericin B deoxycholate and ABCD, are presented. The treatment was successful in seven cases. During treatment with amphotericin B deoxycholate, a rise in serum creatinine was observed in seven patients, hypokalemia in five, and metabolic acidosis in four. After replacing amphotericin B deoxycholate with ABCD, laboratory parameters improved in four of the seven patients with increased creatinine, in four of the five patients with hypokalemia, and in two of the four patients with metabolic acidosis. Infusion-related rigors were observed in four patients receiving amphotericin B deoxycholate and in one patient treated with ABCD. Reversible elevation of liver enzymes was found in one patient receiving ABCD. In this study ABCD proved less toxic than amphotericin B deoxycholate. The efficacy of ABCD alone cannot be assessed because of previous treatment with amphotericin B deoxycholate, but sequential treatment of deep Candida infections with amphotericin B deoxycholate and ABCD seems to be an effective therapeutic modality, especially in patients requiring prolonged administration of amphotericin B.

Topics: Acidosis; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hypokalemia; Male; Middle Aged; Treatment Outcome