amphotericin-b and Hypokalemia

To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations.. A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.. Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN. Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB. Lipid-based formulations of AmB are clinically effective and safe in preventing AIN. However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction. The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations.

Topics: Amphotericin B; Animals; Anti-Infective Agents; Colloids; Diuretics; Humans; Hypokalemia; Lipids; Liposomes; Pharmaceutical Vehicles; Renal Insufficiency

To review the published clinical data assessing the role of amiloride in the prevention of amphotericin B (AmB)induced electrolyte disorders.. A MEDLINE search (January 1966-April 1999) of English-language literature pertaining to AmB, amiloride, potassium, and magnesium was performed. Tertiary sources were also used.. In vivo and in vitro human and animal data and case reports were included due to the lack of published clinical trials.. AmB administration can result in severe hypokalemia and hypomagnesemia requiring chronic supplementation. In one prospective, controlled study of hypokalemia with AmB administration, patients receiving concomitant amiloride had significantly greater potassium concentrations (p < 0.01) and required significantly less potassium supplementation (p < 0.001). Amiloride may also reduce the amount of magnesium supplementation required by sparing elimination through the kidneys.. Amiloride may be considered for the prevention of AmB-induced hypokalemia and hypomagnesemia, especially in patients at high risk for complications resulting from these electrolyte disorders. Further studies are needed to assess concomitant use of other potassium-sparing diuretics and AmB.

Topics: Amiloride; Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Diuretics; Humans; Hypokalemia; Magnesium Deficiency

Topics: Amphotericin B; Antifungal Agents; Humans; Hypokalemia; Mycoses

Amphotericin B (AmB) has been in clinical use for more than 30 yr but has remained the most effective drug for treatment of serious fungal infections. Its use has increased in recent years, as the result of increases in aggressive intensive care support and increased numbers of immunocompromised patients. Nephrotoxic manifestations are common, and this is the major factor limiting the clinical use of the drug. A number of recent studies have contributed to a better understanding of the mechanism by which AmB exerts its nephrotoxic effect. AmB alters cell membrane permeability and probably as a consequence alters tubular and vascular smooth muscle cell function, leading to various tubular transport defects and vasoconstriction. Decreased RBF appears to play a major role in AmB-induced reduction GFR, and recurrent ischemia may be the basis of permanent structural nephrotoxic effects. Salt loading is the only measure proven by controlled prospective study to ameliorate AmB nephrotoxicity in humans. Liposomal AmB and the formulation of an emulsion of AmB in lipid may provide a protective effect based on altering the affinity of AmB for mammalian cell membranes, while preserving high efficacy against fungal cells. However, further studies are needed to evaluate the efficacy and safety of these new AmB formulations.

Topics: Acidosis, Renal Tubular; Amphotericin B; Cell Membrane Permeability; Humans; Hypokalemia; Kidney; Kidney Diseases; Vasoconstriction

Unlike the situation with many antimicrobial agents, there is limited experience with the use of amphotericin B during pregnancy. Although reports of fungal infections during pregnancy have been published, few describe fungemia with either Candida or Torulopsis species. We present a case of fungemia due to Torulopsis glabrata that occurred during pregnancy and that was treated with amphotericin B. Drug concentrations were measured in placental tissue, cord serum, and infant serum at delivery. Although the last dose of amphotericin B was administered 4 weeks before delivery, the concentrations in all three specimens were still within the MIC ranges for most strains of Candida albicans and T. glabrata as measured by broth dilution. We speculate that persistent tissue concentrations of amphotericin B most likely contributed to the sustained hypokalemia in the mother and the increased creatinine level in the infant. In the latter case, placental tissue may have served as the reservoir from which amphotericin B was slowly released into fetal circulation.

Topics: Adult; Amphotericin B; Candidiasis; Creatinine; Female; Fungemia; Humans; Hypokalemia; Infant, Newborn; Placenta; Pregnancy; Pregnancy Complications, Infectious

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

A multicenter, uncontrolled clinical study has been conducted to evaluate the safety, efficacy, and pharmacokinetics of liposomal amphotericin B (L-AMB) in children. In this article, the safety and efficacy of L-AMB are discussed. Subjects were diagnosed with invasive fungal infection (definitely diagnosed cases), possible fungal infection (clinically diagnosed cases), and febrile neutropenia with suspected fungal infection (febrile neutropenia cases). Of the 39 subjects treated with L-AMB, 18 received a definite (11) or clinical (7) diagnosis of invasive fungal infection. In these subjects, excluding one unevaluable subject, L-AMB was effective in nine out of 17 subjects(52.9%). Of 12 febrile neutropenia cases, improvement in clinical symptoms, etc., was observed for six but these were excluded from the efficacy analysis because they concomitantly used medications that may have affected efficacy. The causative fungus was identified in four out of 39 subjects and confirmed to be eliminated by treatment with L-AMB in one subject. Adverse events possibly related to L-AMB (adverse drug reactions) were reported in 36 out of 39 subjects (92.3%). The most commonad verse drug reaction was decreased potassium in 20 out of 39 subjects (51.3%), but all these subjects recovered with appropriate treatment, for example potassium supplementation.In a Japanese Phase II clinical study of adult patients, the incidence of adverse drug reactions was 95.3%(82/86 subjects) and the efficacy was 63.6% (42/66). Taken together, these data indicate that the safety and efficacy of L-AMB are almost the same in pediatric and adult patients.

Topics: Amphotericin B; Antifungal Agents; Child; Child, Preschool; Creatinine; Female; Humans; Hypokalemia; Male; Mycoses; Neutropenia

Invasive mold infections continue to account for significant morbidity and mortality in immunocompromised patients; outcomes are dependent on both underlying host factors and appropriate therapy. The antifungal armamentarium has gradually increased during the past, with liposomal amphotericin B (L-AMB) being an important representative. Still, the question of what dose to use - a maximum tolerated or a minimum effective - has yet to be answered. On this basis, a randomized trial comparing a high-loading dose regimen with a standard dosing of L-AMB (AmBiLoad trial) for primary therapy of mold infections was initiated. No significant differences in response between the treatment groups were detected, although recipients of the 10-mg/kg daily dose experienced higher rates of nephrotoxicity and hypokalemia. Uncontrolled malignancy and allogeneic stem cell transplantation were significantly associated with poor survival. This article analyzes the study, discusses the rationale and the results and concludes that this study supports the routine application of L-AMB.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Dose-Response Relationship, Drug; Double-Blind Method; Hematologic Neoplasms; Humans; Hypokalemia; Nephrotic Syndrome; Neutropenia; Survival Rate; Treatment Outcome

Conventional amphotericin B (c-AmB) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin (FUO). Unfortunately, empirical treatment with c-AmB is hampered by its safety profile, with frequent infusion-related adverse events (IRAEs) and renal toxicity. Amphotericin B lipid complex (ABLC) has been investigated for this indication due to its low toxicity profile. The recommended dose of ABLC is 5 mg/kg/d, which is five to seven times higher than the recommended dose of c-AmB.. This randomized, controlled trial includes 105 adult patients with hematologic malignancies and with FUO after receiving chemotherapy or autologous stem cell transplantation. Patients were randomly allocated to receive ABLC at 1 mg/kg/d or c-AmB at 0.6 mg/kg/d for empirical antifungal therapy.. The incidence of renal toxicity was significantly lower in the ABLC group, compared with c-AmB group: 8% vs. 32%, respectively (P = 0.003). The rates of IRAEs were similar in both groups (73% for ABLC vs. 77% for c-AmB). The overall response rate was 72% for ABLC compared with 48% for c-AmB (P = 0.018). This difference was mainly due to the significantly higher renal toxicity in the c-AmB group. The number of emergent fungal infections and overall mortality were similar in both groups.. This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c-AmB, without differences in the incidence of IRAEs and with similar efficacy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Drug Combinations; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Hypokalemia; Immunocompromised Host; Incidence; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia; Peripheral Blood Stem Cell Transplantation; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

We conducted a trial of oral acetazolamide for the treatment of cryptococcal meningitis in 22 Thai adults with headache and an opening cerebrospinal fluid pressure of >/=200 mm H(2)0. The trial was terminated prematurely because patients who received acetazolamide developed significantly lower venous bicarbonate levels and higher chloride levels and had more-frequent serious adverse events than did subjects who received placebo.

Topics: Acetazolamide; Acidosis; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Diuretics; Double-Blind Method; Female; Headache; Humans; Hypokalemia; Intracranial Hypertension; Male; Meningitis, Cryptococcal; Middle Aged

Nephrotoxicity is the major adverse effect of amphotericin B (AmB), often limiting administration of full dosage. Selective distal tubular epithelial toxicity seems to be responsible for the profound potassium wasting that is a major clinical side effect of treatment with AmB. Potassium depletion also potentiates the tubular toxicity of AmB. This study was designed to assess the ability of spironolactone to reduce potassium requirements and to prevent hypokalemia in neutropenic patients on AmB treatment.. In this study 26 patients with various hematological disorders were randomized to receive either intravenous AmB alone or AmB and oral spironolactone 100 mg twice daily when developing a proven or suspected fungal infection.. Patients receiving concomitant AmB and spironolactone had significantly higher plasma potassium levels than those receiving AmB alone (P = 0.0027). Those patients receiving AmB and spironolactone required significantly less potassium supplementation to maintain their plasma potassium within the normal range (P = 0.022). Moreover, urinary potassium losses were significantly less in patients receiving AmB and spironolactone than those receiving AmB alone (P = 0.040).. This study showed that spironolactone can reduce potassium requirements and prevent hypokalemia by reducing urinary potassium loss in neutropenic patients on AmB treatment.

Topics: Amphotericin B; Antifungal Agents; Humans; Hypokalemia; Kidney Function Tests; Mineralocorticoid Receptor Antagonists; Mycoses; Neoplasms; Neutropenia; Potassium; Spironolactone

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation; Humans; Hypokalemia; Lung; Lung Diseases, Fungal; Middle Aged; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

Amphotericin B colloidal dispersion (ABCD), a novel formulation of amphotericin B and cholesteryl sulfate in a 1:1 ratio, was developed to reduce the toxicity of amphotericin B yet retain its antifungal efficacy. In an open-label trial, ABCD at dosages as high as 6 mg/(kg.d) was administered to 168 patients with documented or presumed systemic mycoses. All patients had responded incompletely to at least 7 days' treatment with conventional amphotericin B (CAB), had experienced CAB-induced nephrotoxic effects, had preexisting renal impairment, or had experienced other CAB-related, treatment-limiting toxic effects. The clinical response to ABCD could be evaluated in 97 patients. Complete clinical response or improvement was noted in 48 (49%) of them after a mean treatment duration of 18.5 days. All 168 enrolled patients were evaluated with regard to safety of the treatment. Even at daily doses as high as 6 mg/kg, and mean and median cumulative doses of 4.0 g and 2.4 g, respectively, ABCD had little renal toxicity: the mean change in serum level of creatinine from baseline to final value was -0.02 mg/dL. Hypokalemia developed in eight patients (5%). This study provides preliminary evidence that ABCD is effective in treating invasive mycoses and lacks the dose-limiting nephrotoxicity of CAB.

Topics: Adult; Amphotericin B; Colloids; Creatinine; Female; Humans; Hypokalemia; Kidney; Male; Mycoses; Safety

The administration of amphotericin B in the conventional prolonged infusion over 4 to 6 hours is complicated by the acute toxicities of fevers and chills in 50% to 90% of patients and the chronic toxicities of increased creatinine levels and hypokalemia in 60% to 80% of patients. To determine the safety and toxicity of rapid infusions, we conducted a prospective, nonrandomized study in patients with clinical indications for antifungal therapy.. Twenty-five granulocytopenic adults with acute leukemia and myelodysplastic syndromes were enrolled in a phase I trial using four sequentially shorter infusion durations: a standard infusion over 4 hours (n = 3) and shortened infusion durations at 3 hours (n = 3), 2 hours (n = 4), and 1 hour (n = 15). Toxicity was assessed by daily examinations of study subjects by one of the study investigators, by documentation of all infusion-related fevers and chills, and by daily monitoring of serum levels of creatinine, potassium, magnesium, and aspartate aminotransferase.. Temperatures greater than 38 degrees C occurred in 16 of 25 (64%) patients, but only two had temperatures exceeding 40 degrees C. Chills were observed in 13 of 25 (56%) patients, but only one had severe symptoms. Serum creatinine increased more than 0.5 mg/dL (44.20 mumol/L) above the pretreatment baseline in 17 of 25 (68%) patients, and the absolute creatinine level was greater than or equal to 2.0 mg/dL (176.8 mumol/L) in 10 of 25 (40%) patients. Serum potassium levels dropped below the normal limit of 3.5 mEq/L (3.5 mmol/L) in all patients, but no patient had potassium levels below 2.5 mEq/L (2.5 mmol/L). Intravenous potassium supplementation was administered to all patients and exceeded 100 mEq/d in 12 of 25 (48%) patients.. Rapid infusions of amphotericin B are safe, are associated with similar toxicity as prolonged infusions, and facilitate inpatient care by decreasing nursing time needed for administration and minimizing scheduling conflicts with other necessary intravenous medications. Shorter infusions also facilitate outpatient and home administration of amphotericin B.

Topics: Aged; Amphotericin B; Bone Marrow; Chemical and Drug Induced Liver Injury; Drug Evaluation; Female; Fever; Humans; Hypokalemia; Infusions, Intravenous; Kidney Diseases; Magnesium; Male; Middle Aged; Pilot Projects; Prospective Studies; Time Factors; Treatment Outcome

Twenty neutropenic patients with various haematological disorders were randomised prospectively to receive either intravenous amphotericin B alone or amphotericin B and oral amiloride 5 mg twice a day for treatment of confirmed or suspected fungal infection. Patients receiving amiloride had a significantly higher plasma potassium (p less than 0.01), a significantly lower urinary potassium loss (p less than 0.01), and required significantly less potassium chloride supplementation to maintain their plasma potassium within the normal range (p less than 0.001). Amiloride was well tolerated, had no clinically important side effects, and provided effective control of plasma potassium in patients treated with amphotericin B.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amiloride; Amphotericin B; Clinical Trials as Topic; Humans; Hypokalemia; Middle Aged; Mycoses; Neutropenia; Potassium; Random Allocation

Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period.. Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC).. The first hospitalization time of Group I (median: 25 days, IQR: 20-34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29-62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43-77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43-7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23-11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004).. AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Hypokalemia; Meningitis, Cryptococcal; Retrospective Studies; Treatment Outcome; Voriconazole

Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood.. Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation.. We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584-2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400-2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358).. Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.

Topics: Acute Kidney Injury; Aged; Amphotericin B; Antifungal Agents; Dietary Supplements; Female; Humans; Hypokalemia; Male; Potassium; Regression Analysis; Retrospective Studies

Liposomal amphotericin (L-AMB) is a widely used broad-spectrum antifungal drug. Although L-AMB demonstrates better safety compared with amphotericin, renal dysfunction and hypokalemia are well-known adverse effects of L-AMB.. We analyzed 56 episodes in 40 children and adolescents who received L-AMB therapy to determine risk factors of hypokalemia.. Hypokalemia (<3.0 mEq/L continuously for more than 2 episodes) was observed in 31 of 56 episodes (55.4%). The median onset of hypokalemia was at 10 days on L-AMB (range, 3-54 days), and the median cumulative dose of L-AMB at occurrence of hypokalemia was 25 mg/kg (range, 10-167.5 mg/kg). None of the patients with hypokalemia had solid tumors, and they had significantly higher estimated glomerular filtration rates than those with normokalemia (P = 0.013). Seven of 25 (28.0%) patients in the normokalemia group and 1 of 31 (3.2%) patients in the hypokalemia group had eGFRs of <90 mL/min/1.73 m(2) (P = 0.017).. Although the reason for the association between estimated glomerular filtration rates and hypokalemia is unclear, assessing the estimated glomerular filtration rates before L-AMB administration may predict the development of hypokalemia.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Glomerular Filtration Rate; Humans; Hypokalemia; Infant; Infant, Newborn; Invasive Fungal Infections; Japan; Male; Risk Factors; Young Adult

Liposomal amphotericin B (L-AMB) has the potential to cause two major adverse events, renal dysfunction and serum potassium abnormality; however, appropriate clinical management of these events remains unclear. We retrospectively analyzed data regarding 128 hematology patients who received L-AMB in our institute and examined the association between clinical characteristics and renal dysfunction or serum potassium abnormality. We found that the median weight-normalized dose of L-AMB was 2.69mg/kg and the median administration period was 16days. The overall occurrence rates of renal dysfunction and hypokalemia were 55.7% and 76.6%, respectively. Multivariate analysis revealed that pre-existing renal dysfunction (P=0.017) and concomitant use of nephrotoxic (P<0.0001) or antifungal drugs (P=0.012) were independent risk factors for renal dysfunction. A higher infusion volume did not mitigate the risk of renal dysfunction. Hypokalemia occurred significantly less often in men (P=0.028) and in patients who concomitantly used nephrotoxic drugs (P=0.013). Approximately 40% of the adverse events were improved at 30days after L-AMB termination and there was no significant association between these adverse events improvement and L-AMB dosage or infusion volume. Of note, hyperkalemia was observed in more patients who received allogeneic hematopoietic stem cell transplantation (P=0.0303) and concomitant treatment with nephrotoxic drugs (P=0.0281). These results suggest that imprudent reduction of L-AMB dose or redundant intravenous infusion may have minimal benefit for critical patients with suspected invasive fungal infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Hematologic Diseases; Humans; Hyperkalemia; Hypokalemia; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycoses; Retrospective Studies; Risk Factors; Young Adult

Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB-induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients.. Seventy-eight hematologic patients with a first administration of L-AMB were enrolled in the study. Eleven patients who had serum potassium levels <3.0 mmol/L before L-AMB administration and 12 patients who received L-AMB administration within 3 days were excluded. Patients who had a serum potassium level <3.0 mmol/L during L-AMB administration were classified into a hypokalemia group (n = 26), and those who had a serum potassium level ≥3.0 mmol/L were classified into a non-hypokalemia group (n = 29). The patient characteristics were analyzed retrospectively. In addition, the usefulness of potassium supplementation was analyzed for those patients who received potassium formulations (non-hypokalemia group, n = 15; hypokalemia group, n = 24).. Twenty-six patients had hypolalemia after L-AMB administration. Hypokalemia with serum potassium levels <3.0 mmol/L was observed ~7 days after starting L-AMB administration. The patient characteristics, L-AMB dose, and L-AMB administration period did not differ between the 2 groups. In the patients who received potassium formulations, the period between starting L-AMB administration and starting potassium supplementation was significantly shorter in the non-hypokalemia group than in the hypokalemia group (median, 0 vs 4 days, respectively; P < 0.01); the potassium dose was not different between the 2 groups. A receiver-operating characteristic curve revealed that the cutoff time for the start of potassium supplementation to reduce the incidence of L-AMB-induced hypokalemia was 3 days. Multivariate logistic regression analysis revealed that beginning potassium supplementation within 2 days from the start of L-AMB administration was an independent factor reducing the risk of L-AMB-induced hypokalemia (odds ratio, 0.094 [95% CI, 0.019-0.47]).. This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Humans; Hypokalemia; Male; Middle Aged; Potassium; Retrospective Studies; Risk Factors; Young Adult

Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infections after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our institute. Within the entire cohort, 42 patients (88%) received L-AMB as empirical or preemptive therapy. The median daily dose of L-AMB and the median cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62 to 2.60 mg/kg/day) and 30.6 mg/kg (range, 0.7 to 241.5 mg/kg), respectively. The median duration of L-AMB administration was 21.5 days (range, 1 to 313 days). A documented breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and 43 patients (90%) survived for at least 7 days after the end of L-AMB treatment. Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during L-AMB treatment. However, no patient developed an increase in serum creatinine levels of grade 3 or higher. In univariate analyses using a logistic regression model, a duration of L-AMB treatment of more than 21 days and a cumulative dose of L-AMB of more than 30 mg/kg were significantly associated with nephrotoxicity and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and effective in adult patients undergoing CBT.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Cord Blood Stem Cell Transplantation; Female; Humans; Hypokalemia; Liposomes; Male; Middle Aged; Mycoses; Retrospective Studies; Young Adult

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Bangladesh; Child; Female; Humans; Hypokalemia; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Rhabdomyolysis; Young Adult

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

Literature provides much evidence regarding liposomal amphotericin B treatment for fungal infections in neonates and infants. Relevant data regarding critically ill paediatric patients of older age are scarce. We aimed to present our experience regarding liposomal amphotericin B use in critically ill paediatric patients from a tertiary-care paediatric hospital in Athens, Greece.. We prospectively identified all paediatric patients who received treatment with liposomal amphotericin B in the intensive care unit of a tertiary-care paediatric hospital during a 3-year period (2005-2008). Data were retrieved from the evaluation of the available medical records.. Twenty-three (nine females, mean age: 26·4 months, range: 5-39 months) critically ill paediatric patients were included; 12 had malignancy. In 16 of the 23 included children, liposomal amphotericin B was administered for the treatment of confirmed fungal infections (all but one were invasive), whereas in seven patients, it was used as pre-emptive treatment. One patient received voriconazole concomitantly. Eleven of the 16 children with documented infections were cured; five improved. Six of the seven children who received pre-emptive treatment also showed clinical improvement. Nine deaths were noted, all attributed to underlying diseases. Two cases of hepatotoxicity and one case of nephrotoxicity (all leading to drug-discontinuation) occurred. Seven and five cases of mild reversible hypokalaemia and hyponatraemia, respectively, were also noted.. According to the findings of our small case series, liposomal amphotericin B may provide a useful treatment option for fungal infections of vulnerable critically ill paediatric patients with considerable comorbidity.

Topics: Amphotericin B; Antifungal Agents; Chemical and Drug Induced Liver Injury; Child, Preschool; Comorbidity; Drug Monitoring; Female; Greece; Hospitals, Pediatric; Humans; Hypokalemia; Hyponatremia; Infant; Intensive Care Units, Pediatric; Liposomes; Male; Mycoses; Neoplasms; Prospective Studies; Renal Insufficiency

Amphotericin B (AmB) traditionally has been the mainstay of therapy for children with candidemia but is associated with drug-related toxicities (DRT). Studies investigating the risk factors for AmB DRT in children are limited.. A retrospective review of patients aged 6 months to ≤18 years with candidemia who received ≥1 dose of AmB from 2003 to 2009 was conducted at Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug dosages, laboratory adverse effects and infusion-related side effects (INFRT) were recorded.. A total of 223 episodes of candidemia occurred in 179 patients. AmB was administered in 172 (77%) episodes. Amphotericin B deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83% (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62) and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n = 33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients with lower baseline creatinine clearance were at increased risk of having nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004). Nephrotoxicity was less likely in patients who received immunosuppressants (P = 0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were independently associated with hypokalemia. The receipt of premedication was independently associated with a lower likelihood of INFRT (P ≤ 0.0001). It is important to note that most AmB-related DRT was quickly reversible.. AmB-associated DRT was common and reversible in our nonneonatal pediatric population. Prospective studies are required to further evaluate risk factors and determine whether they are modifiable.

Topics: Adolescent; Amphotericin B; Analysis of Variance; Antifungal Agents; Candidemia; Child; Child, Preschool; Female; Humans; Hypokalemia; Infant; Kidney Diseases; Male; Retrospective Studies; Risk Factors

Liposomal amphotericin B (LAMB) is frequently administered in NICU to preterm infants <1500 g at birth (VLBW) for treatment of systemic fungal infections (SFI). Concerns exist on safety and tolerability of such drug in patients who are at risk for renal function impairment due to their prematurity.. To assess the occurrence of renal function impairment related to LAMB in a 10-year cohort of VLBW neonates treated with this drug.. Through database search of clinical charts, all VLBW neonates admitted to a 3(rd) level NICU in the years 1998-2007 and undergoing treatment with LAMB were identified. The occurrence of LAMB-attributable renal toxicity was investigated; infants withdrawn from treatment for development of adverse effects or toxicity were identified.. In the study period, 71 of 792 admitted VLBW neonates (8.9%) underwent antifungal treatment with LAMB administered at the recommended dosages (3-to-5 mg/kg/day). Mean duration of treatment was 14 (±9) days, mean cumulative dose given was 58 (±25) mg/kg per infant. Renal compromise, defined as hypokalaemia, and/or elevated creatinine serum levels, and/or decreased urine output, occurred in 2 of 71 (2.8%) treated patients, by 5 (±3) mean days after treatment initiation. In both patients LAMB was withdrawn; renal function impairment was only mild and transient, and normal renal function was restored at discharge. No other significant adverse effects were recorded in any treated neonate.. LAMB is generally safe and well tolerated in VLBW neonates. The occurrence of LAMB-related nephrotoxicity appears to be uncommon, mild and transient.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cohort Studies; Creatinine; Fluconazole; Humans; Hypokalemia; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Kidney; Kidney Diseases; Kidney Function Tests; Mycoses; Premature Birth; Retrospective Studies; Sepsis

Liposomal amphotericin B (L-AmB), which was developed to reduce side effects, has been shown to have a better safety profile than both the deoxycholate and lipid complex forms of amphotericin B; however, the frequency of major side effects is still unclear. Thus, the aim of the present study was to assess retrospectively the frequency of L-AmB-induced anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia as well as the relationship between daily dose of L-AmB and these side effects. A low red blood cell (RBC) count (post-/pre-treatment) and anaemia were observed in 7 and 10 of 21 adult patients, respectively. Thrombocytopenia was observed in 11 of 19 adult patients. Doses of L-AmB that are estimated to cause side effects of a low RBC count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0mg/kg/day, respectively. Nephrotoxicity was observed in 6 of 22 patients. Variations of total bilirubin, γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase used as indices of hepatotoxicity were observed in 6, 7, 8 and 8 of 22 patients, respectively. Hypokalaemia was observed in 4 of 9 patients; however, nephrotoxicity, hepatotoxicity and hypokalaemia were not caused in a dose-dependent manner. In conclusion, the present analyses showed that L-AmB dose-dependently induced anaemia and thrombocytopenia in adult patients. It is important to pay attention to causing anaemia and thrombocytopenia when patients are receiving L-AmB at doses of >3.3mg/kg/day and >3.0mg/kg/day, respectively.

Topics: Aged; Amphotericin B; Anemia; Antifungal Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Thrombocytopenia

We have retrospectively analyzed the safety of 4 hours administration of liposomal amphotericin B (L-AMB) compared to less than or equal to 3 hours administration in patients with chronic necrotizing pulmonary aspergillosis (CNPA). The elevation of serum creatinine in the group with 4 hours administration of L-AMB in patients with CNPA was equal to the group with shorter administration time (less than or equal to three hours). During the administration of L-AMB, the group with 4 hours administration of LAMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment than the group with shorter administration time. Additionally, white cell counts, platelet counts, serum creatinine, AST, ALT were not significantly different between L-AMB 4 hours administration group and less than or equal to 3 hours administration group. As the group with 4 hours administration of L-AMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment, this modality can be one of the safer ways in the treatment of CNPA. As L-AMB is one of the fungicidal agents, 4 hours administration of L-AMB can be an optimal way of treating CNPA.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Chronic Disease; Female; Humans; Hypokalemia; Infusions, Intravenous; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Potassium; Retrospective Studies; Time Factors; Treatment Outcome

Hypokalemia can result in life-threatening complications if not treated appropriately. Although hypokalemia is a frequent adverse effect of amphotericin B therapy, there are no reports in the pediatric literature on hypokalemia-associated rhabdomyolysis induced by this drug. A ten-year-old boy with a history of one week amphotericin B treatment was admitted with weakness of the lower extremities, inability to walk and calf pain. Laboratory tests showed a serum potassium of 1.7 mEq/L and a serum creatinine phosphokinase of 3937 U/L plus myoglobulinuria. Following fluid expansion and intravenous potassium replacement, the patient progressed to achieve full regression of muscular weakness after one week. This report highlights hypokalemia as a rare cause of rhabdomyolysis. Patients on amphotericin B should be checked for this rare yet potentially life-threatening complication.

Topics: Amphotericin B; Anti-Bacterial Agents; Child; Follow-Up Studies; Humans; Hypokalemia; Male; Rhabdomyolysis; Surgical Wound Infection

Amphotericin B-induced nephrotoxicity is frequent, severe and associated with an increased risk of death. Patients with underlying renal disease are considered to be at high risk for amphotericin B nephrotoxicity. Amphotericin B is a molecule that is highly protein bound over a wide range of protein and drug concentrations, including those seen in patients with >or= 3 + proteinuria. We hypothesized that amphotericin B treatment in patients with proteinuria will be associated with less hypokalaemia than patients with non-proteinuric renal disease.. Thirty-six subjects who received amphotericin B deoxycholate were studied retrospectively. Twenty-five patients with proteinuria < 3 g/L and 11 with proteinuria >or= 3 g/L were compared.. Hypokalaemia (K+ < 3.5 mmol/L) developed in 47.2% (17/36) of our cohort of patients. There was a 64% (16/25) incidence of hypokalaemia in the group with < 3 g/L of proteinuria in contrast to an incidence of 9.1% (1/11) in the other group.. In our study, heavy proteinuria appears to protect the tubular luminal membrane by decreasing the luminal concentration of free drug available to bind with the membrane. Our findings redefine the patient population deemed to be at risk of developing amphotericin B nephrotoxicity. This ensures the benefit of this important antifungal treatment option to patients with heavy proteinuria who might otherwise not be administered this drug due to the presence of pre-existing kidney disease.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Mycoses; Proteinuria; Retrospective Studies; Risk

We describe drug-drug interactions (DDIs) encountered with antifungals in clinical practice.. Retrospective observational study of hospitalized adults receiving systemic antifungal treatment in the intensive care unit (ICU) and in the infectious diseases unit (IDU) of the University Hospital of Bordeaux, France between 1996 and 2001. All treatment episodes with antifungal agent were examined and all prescribed concomitant medication identified for potential drug-drug interactions (PDDI)-serious events occurring during treatment were adjudicated for clinical DDI.. There were 150 treatment episodes with antifungal agent in 105 patients. Fluconazole was used in 48% of the treatment episodes, amphotericin B in 46%, itraconazole in 4.7% and flucytosine in 1.3%. One hundred and sixteen PDDIs were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%) or itraconazole (1.7%). Of these, 22 were associated with a clinical evidence of adverse interaction (hypokalemia, increased creatininemia or nephrotoxicity). All these clinical drug-drug interactions (CDDIs) were with amphotericin B. They were due to furosemide (36.4%), cyclosporine (31.8%) and hydrocortisone (18.2%). PDDIs were mostly associated with leukaemia (40.4%), HIV infection (24.6%) and cancer (10.5%).. In ICU and IDU, systemic antifungal treatments lead to many PDDIs, mainly related to the type of antifungal used and to the pathology treated. Clinical DDI seem more common with amphotericin.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Cyclosporine; Drug Interactions; Female; Fluconazole; France; Furosemide; HIV Infections; Hospitals, University; Humans; Hydrocortisone; Hypokalemia; Intensive Care Units; Itraconazole; Kidney Diseases; Leukemia; Male; Middle Aged; Neoplasms; Retrospective Studies

Amiloride was administered to 19 oncology patients exhibiting marked amphotericin B-induced electrolyte wasting. Mean serum potassium concentrations increased in the 5 days preceding and following administration (3.4 +/- 0.5 versus 3.9 +/- 0.8 mmol/L, P = 0.002). A trend towards decreased potassium supplementation was also observed (48.0 +/- 66.5 versus 29.4 +/- 43.2 mmol/day, P = 0.12). Amiloride is a therapeutic option to decrease potassium wasting in patients being treated with amphotericin B.

Topics: Adult; Aged; Amiloride; Amphotericin B; Antifungal Agents; Humans; Hypokalemia; Magnesium; Middle Aged; Potassium

Amphotericin B lipid complex (ABLC) has been investigated as an empirical antifungal treatment for neutropenic patients with persistent fever of unknown origin (FUO). We studied the safety and efficacy of low dose ABLC (1 mg/kg/day) for empirical treatment of neutropenic FUO. Sixty-one patients with hematologic malignancies developing 69 episodes of neutropenic FUO after chemotherapy or hematopoietic stem cell transplantation were included in the study. The median patient age was 47 years (18-68). The median duration of neutropenia (< 0.5 x 10(9)/l) was 17 days (7-45) and the median duration of ABLC therapy was 8 days (2-19). Thirteen patients (19%) suffered from mild to moderate infusion-related adverse events. Creatinine levels were stable in 42 cases (61%), improved in 9 (13%) and deteriorated in 18 (26%), with no other significant toxicities. Among 67 evaluable episodes, the response rate (resolution of fever during the period of neutropenia without developing a fungal infection) was 67%, while 33% were treatment failures. Low-dose ABLC is safe, well tolerated and seems to be at least as effective as c-AmB for empirical antifungal therapy of FUO. Randomized trials at this dose level comparing ABLC with c-AmB or other lipid formulations are warranted.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antiviral Agents; Drug Combinations; Female; Fever; Hematologic Neoplasms; Humans; Hypokalemia; Kidney; Liver; Male; Middle Aged; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols

Topics: Amphotericin B; Drug Interactions; Humans; Hypokalemia; Mineralocorticoid Receptor Antagonists; Neutropenia; Potassium; Spironolactone

The use of conventional amphotericin B is limited by toxicity, side-effects, drug interactions and the need for large infusion volumes, especially for infants. Use of liposomal amphotericin B (AmBisome) in 15 paediatric BMT patients with primary immunodeficiency (PID) was therefore studied. Adverse clinical reactions to AmBisome and biochemical profiles were monitored daily for 2 weeks before, during and after each treatment episode. Fungal cultures were obtained weekly and when patients were pyrexial. There were 18 treatment episodes. Mean daily dose was 5 mg/kg (2-6 mg/kg). Mean duration of treatment was 25 days (5-90 days). Clinical reactions to AmBisome were observed in one infant who had a pyrexia of 38 degrees C. One of the 15 infants had a significant increase in creatinine level while on concomitant nephrotoxic therapy. Four developed mild hypokalaemia on AmBisome which resolved with increased potassium supplementation. AmBisome was well tolerated and without significant renal or hepatic toxicity in severely ill immunodeficient infants receiving multiple nephrotoxic and hepatotoxic drugs such as cyclosporin, vancomycin and foscarnet.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child, Preschool; Creatinine; Drug Interactions; Drug Tolerance; Female; Humans; Hypokalemia; Immunologic Deficiency Syndromes; Infant; Kidney; Liposomes; Liver; Male; Potassium, Dietary; Retrospective Studies; Safety; Severe Combined Immunodeficiency

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

We describe six patients with invasive fungal infections who received large cumulative doses (22.3-73.6 g) of amphotericin B lipid complex (ABLC) over 21-121 weeks. The drug was well tolerated at these very large doses, and there was limited toxicity. Collectively, these patients received ABLC therapy for a mean of 53.8 weeks (range, 21-121 weeks). The mean serum creatinine level at the start of ABLC therapy was 1 mg/dL (range, 0.4-1.9 mg/dL), and at the end of therapy this level was 1.5 mg/dL (range, 1.0-2.0 mg/dL). Over the course of therapy, only two patients had serum creatinine levels of > or = 2 mg/dL, with transient peak serum creatinine levels of 3.5 and 2.8 mg/dL, respectively. Several patients required replacement therapy with oral or intravenous potassium. None of the patients had ABLC-associated toxic effects necessitating discontinuation of the treatment. ABLC may be given in substantially larger doses than conventional amphotericin B, and very high doses of ABLC that are administered over several months appear to be relatively less toxic than those of conventional amphotericin B.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Creatinine; Drug Tolerance; Female; Humans; Hypokalemia; Kidney; Lipids; Male; Middle Aged; Mycoses; Potassium; Time Factors

The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.

Topics: Adolescent; Amphotericin B; Anemia; Child; Child, Preschool; Female; Heart; Humans; Hypokalemia; Infant; Kidney; Liver; Male; Mycoses; Neoplasms; Neutropenia; Thrombocytopenia

Topics: Administration, Oral; Amphotericin B; Arrhythmias, Cardiac; Brain Diseases; Cytosine; Flucytosine; Gastrointestinal Diseases; Humans; Hypokalemia; Injections, Intravenous; Injections, Spinal; Intestinal Perforation; Kidney Diseases; Meningitis; Mycoses; Paralysis; Radiculopathy; Vision Disorders

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Amphotericin B; Blastomycosis; Carbon Dioxide; Glomerular Filtration Rate; Histoplasmosis; Humans; Hydrogen-Ion Concentration; Hypokalemia; Kidney Diseases; Kidney Tubules; Mycoses; Partial Pressure; Potassium; Uric Acid

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Amphotericin B; Blastomycosis; Carbon Dioxide; Glomerular Filtration Rate; Histoplasmosis; Humans; Hydrogen-Ion Concentration; Hypokalemia; Kidney Diseases; Kidney Tubules; Mycoses; Partial Pressure; Potassium; Uric Acid

Topics: Amphotericin B; Blastomycosis; Cardiomegaly; Heart Failure; Histoplasmosis; Humans; Hydrocortisone; Hypokalemia; Lung Diseases, Fungal; Male; Middle Aged; Potassium; Sodium; Water-Electrolyte Balance

Topics: Adolescent; Amphotericin B; Calcium; Chlorides; Creatine Kinase; Female; Humans; Hypokalemia; Meningitis; Muscular Diseases; Potassium

Topics: Adolescent; Aged; Amphotericin B; Anemia; Blastomycosis; Chemical Phenomena; Chemistry; Humans; Hypokalemia; Kidney Diseases; Male; Microbial Sensitivity Tests

Topics: Adult; Amphotericin B; Cryptococcosis; Humans; Hypokalemia; Kidney; Kidney Concentrating Ability; Male; Meningitis; Muscular Diseases; Myoglobinuria; Potassium; Potassium Chloride

Topics: Adult; Age Factors; Aged; Amphotericin B; Anemia; Blood Urea Nitrogen; Creatinine; Female; Follow-Up Studies; Hematocrit; Humans; Hypokalemia; Kidney; Male; Middle Aged

Topics: Amphotericin B; Anemia; Blood Urea Nitrogen; Coccidioidomycosis; Drug Therapy; Fungi; Hypokalemia; Lung Diseases, Fungal; Toxicology; Urea

Topics: Amphotericin B; Blood; Coccidioidomycosis; Humans; Hypokalemia; Kidney Diseases; Muscular Diseases; Paralysis; Pathology; Potassium; Statistics as Topic; Toxicology; Urine

Topics: Amphotericin B; Anaphylaxis; Anemia; Anuria; Blushing; Feeding and Eating Disorders; Fever; Headache; Heart Failure; Humans; Hypokalemia; Kidney Diseases; Liver Diseases; Meningitis; Nausea; Pain; Paralysis; Paresthesia; Phlebitis; Seizures; Thrombocytopenia; Toxicology; Ventricular Fibrillation; Vertigo; Vomiting

Studies of 47 patients with intravenous amphotericin B revealed some impairment of renal function in all cases. Azotemia developed in 46 cases. Microscopic examination in eight cases showed damage to the distal renal tubule. Profound hypokalemia was recognized in two cases; and symptoms suggesting hypokalemia, which were generally ameliorated by potassium administration, were noted in most cases. It is postulated that the initial potassium loss is due to a "tubular leak" and that subsequent potassium depletion leads to further tubular damage. Mild to severe anemia developed in all cases during therapy. Serial red cell indices, bone marrow examinations and red cell survival studies indicated that hemolysis, rather than bone marrow depression, was responsible.The decision to treat, to modify therapy or to terminate treatment must be made on the basis of severity of disease, probability of progression, and renal status.

Topics: Amphotericin B; Anemia; Anemia, Hemolytic; Humans; Hypokalemia; Kidney; Kidney Tubules; Kidney Tubules, Distal; Male