Liposomal Amphotericin B for Empirical Therapy in Patients with Persistent Fever and Neutropenia

Walsh, Thomas J.; Finberg, Robert W.; Arndt, Carola A.S.; Hiemenz, John W.; Schwartz, Cindy L.; Bodensteiner, David; Pappas, Peter G.; Seibel, Nita L.; Greenberg, Richard N.; Dummer, Stephen; Schuster, Mindy G.; Holcenberg, John S.; Dismukes, William E.

doi:10.1056/nejm199903113401004

Cited by 1,103 publications

(745 citation statements)

References 30 publications

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“…This practice is based upon the results of clinical trials that have demonstrated reductions of 50-75% in the incidence of ARF [13][14][15][16][17]. In these studies the development of ARF, usually defined as a 50% rise in the basal serum creatinine levels and a peak creatinine level higher than 2.0 mg/dL, occurred in 34% to 49% of the patients.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies published during the last two decades have shown that nephrotoxicity can be prevented by the use of sodium loading [4,[7][8][9][10][11], slowing drug infusion [12] and through the use of liposomal or lipid-complex amphotericins [13][14][15][16][17].…”

mentioning

confidence: 99%

“…Based on the results of clinical trials, liposomal amphotericin has been recommended for the prevention of acute renal failure (ARF) [13][14][15][16][17]. These studies included a largely unselected population of patients, with many of them being treated at intensive care units, using vasoactive drugs, and with multiple risk factors for developing ARF.…”

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confidence: 99%

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Amphotericin B-related nephrotoxicity in low-risk patients

Berdichevski¹,

Luis²,

Crestana³

et al. 2006

Braz J Infect Dis

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Introduction. Amphotericin B (AmphoB) is the drug of choice for treatment of severe fungal illnesses; however, it is very nephrotoxic. Modified (less toxic) amphotericins are very expensive. In low-risk patients, saline loading would be enough to prevent significant loss of renal function. Material and Methods. Patients with normal renal function and within the first 24 hours of treatment with AmphoB were prospectively enrolled in the study. Patients in intensive care units or who were using vasoactive drugs were excluded. Saline loads were infused before and after the AmphoB treatment. Blood and urine analyses were made at the beginning and at the end of the treatment. Serum creatinine was repeated 30 days after the end of the AmphoB treatment. Results. The mean increase in serum creatinine in the 48 patients was 0.3 (0.18-0.41) mg/dL, due to a mean decrease of 25 (12.8-36.9) mL/min of creatinine clearance (CrCl). Acute renal failure, defined as an increase of more than 50% of the baseline creatinine, occurred in 15 patients (31%). Patients that were on antibiotics, in post-chemotherapy status or those submitted to bone marrow transplantation had the highest risk. Mean serum creatinine and the CrCl levels were no different from baseline values after 30 days. Conclusion. In low-risk patients, the use of AmphoB with prophylactic sodium chloride loading was associated with a small and reversible decrease in renal function. Due to its high cost the use of more expensive therapies for this type of patient does not seem to be justified.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Amphotericin B-related nephrotoxicity in low-risk patients

Berdichevski¹,

Luis²,

Crestana³

et al. 2006

Braz J Infect Dis

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“…This lipid formulation has a favorable toxicity profile when compared to conventional amphotericin B deoxycholate [2][3][4] and has been approved for use at dosages ranging from 3 to 6 mg/kg/day for indications including empirical therapy of persistent febrile neutropenia, systemic aspergillus, candida, and cryptococcus infections, visceral leishmaniasis, and cryptococcal meningitis in HIV infected patients. The improved safety and tolerability of this formulation have allowed for the use of increasingly higher dosages for the treatment of refractory infections [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy

Lane

Rehak

Hortin

et al. 2008

Clinica Chimica Acta

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Background-Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia.Methods-Serum samples from the index patient were analyzed for Pi content by our laboratory's primary analyzer (Synchron LX20 ) and by an alternate analyzer (Vitros). Clear and lipemic serum pools, and normal saline, were spiked with L-AMB and analyzed by the LX20 Pi method. Ultrafiltration studies were performed on patient and spiked sera.Results-Increased Pi values were obtained only from the LX20 analyzer. There was a direct linear relationship between the concentration of L-AMB in the spiked samples and the LX20 Pi results, indicating a 0.9 mmol/l Pi increase for every 100 mg/l increase in L-AMB. Ultrafiltration normalized the Pi results.Conclusion-Serum Pi results may be falsely increased in patients receiving L-AMB when measured by the LX20 analyzer. This novel cause of pseudohyperphosphatemia is due to interference of L-AMB with the method and is corrected by ultrafiltration of the specimen. Since the LX20 1 Presented in part at the

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“…Empirical antifungal therapy is recommended to patients who have persistent neutropenic fever in spite of antibacterial therapy and have progressive pulmonary infiltrates associated with invasive aspergillosis by serial CT scanning to achieve a better outcome [4]. However, IFI was demonstrated in 4 % of patients who comprised only 22-34 % of the neutropenic patients who had cancer and received an antifungal drug according to established criteria [5].…”

Section: Introductionmentioning

confidence: 99%

Novel Antifungal Drugs Against Fungal Pathogens: Do They Provide Promising Results for Treatment?

Gedık

Şimşek

Yıldırmak

et al. 2014

Indian J Hematol Blood Transfus

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The febrile neutropenia episodes of hematological patients and their outcomes were evaluated with respect to fungal pathogens and antifungal therapy in this retrospective study. All patients, who were older than 14 years of age and developed at least one neutropenic episode after chemotherapy due to hematological cancer from November 2010 to November 2012, were included into the study. We retrospectively collected demographic, treatment, and survival data of 126 patients with neutropenia and their 282 febrile episodes. The mean Multinational Association for Supportive Care in Cancer score was 17.18 ± 8.27. Systemic antifungal drugs were initiated in 22 patients with 30 culture-proven invasive fungal infections (IFIs), 25 attacks of 19 patients with probable invasive pulmonary aspergillosis (IPA), 42 attacks of 38 patients with possible IPA, and 31 attacks of 30 patients with suspected IFI. Voriconazole (VOR), caspofungin and liposomal amphotericin B were used to treat 72 episodes of 65 patients, 45 episodes of 37 patients and 34 episodes of 32 patients as a first-line therapy, respectively. Unfavorable conditions of our hematology ward are thought to increase the number of cases with invasive pulmonary aspergillosis and VOR use. It should be taken into consideration that increased systemic and per oral VOR usage predisposes patients to colonization and infection with azole-resistant fungal strains. Catheters should be removed in cases where patients' conditions are convenient to remove it. Acute myeloblastic leukemia cases that are more likely to develop invasive fungal infections should be monitored closely for early diagnosis and timely initiation of antifungal drugs which directly correlates with survival rates.

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Liposomal Amphotericin B for Empirical Therapy in Patients with Persistent Fever and Neutropenia

Abstract: Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.

Cited by 1,103 publications

References 30 publications

Amphotericin B-related nephrotoxicity in low-risk patients

Amphotericin B-related nephrotoxicity in low-risk patients

Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy

Novel Antifungal Drugs Against Fungal Pathogens: Do They Provide Promising Results for Treatment?

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