Prevention of fungal infections in patients with cancer with amphotericin B

Johansen HK, Gøtzsche PC

Published Online:

November 9, 2011

Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of acquiring fungal infections. Such infections can be life-threatening. Antifungal drugs are therefore often given prophylactically to such patients, or when they have a fever. The review found that lipid formulations of amphotericin B had less adverse effects (less nephrotoxicity and fewer dropouts) than conventional amphotericin B. However, it is not clear whether there are any advantages of these formulations if conventional amphotericin B is administered under optimal circumstances.

Abstract (click to read)

Background:

Objectives:

To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2007, PubMed (November 2007) and the reference lists of articles. We searched the proceedings of the ICAAC (from 1990 to 2007), General Meeting of the ASM (from 1990 to 2007), and the European Congress of Clinical Microbiology and Infectious Diseases (1995 to 2007) and contacted researchers in the field. For the 2011 update we searched PubMed from 1966 to 18 July 2011 and the reference lists of articles.

Selection criteria:

Randomised clinical trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B.

Data collection and analysis:

The two review authors independently assessed trial eligibility, risk of bias and abstracted data.

Main results:

We found 12 trials (1895 patients). Lipid-based amphotericin B was not more effective than conventional amphotericin B for mortality (relative risk (RR) 0.83, 95% confidence interval (CI) 0.62 to 1.12), but decreased invasive fungal infection (RR 0.65, 95% CI 0.44 to 0.97), nephrotoxicity, defined as a 100% increase in serum creatinine (RR 0.45, 95%CI 0.37 to 0.54), and number of dropouts (RR 0.78, 95%CI 0.62 to 0.97).

For the drug used in most patients, AmBisome (3 trials, 1149 patients), there was no significant difference in mortality (RR 0.74, 95% CI 0.52 to 1.07) whereas it tended to be more effective than conventional amphotericin B for invasive fungal infection (RR 0.63, 95% CI 0.39 to 1.01, P = 0.053).

AmBisome, amphotericin B in Intralipid (6 trials, 379 patients), amphotericin B colloidal dispersion (ABCD) (2 trials, 262 patients), and amphotericin B lipid complex (ABLC) (1 trial, 105 patients) all decreased the occurrence of nephrotoxicity, but conventional amphotericin B was rarely administered under optimal circumstances. For the 2011 update no additional trials were identified for inclusion.

Authors' conclusions:

It is not clear whether there are any advantages of lipid-based formulations if conventional amphotericin B is administered under optimal circumstances and their high cost prohibits routine use in most settings. There is a need for large trials comparing lipid-based formulations of amphotericin B with conventional amphotericin B given in the same dose, with routine premedication for prevention of infusion-related toxicity, and with supplementation with fluid, potassium and magnesium for prevention of nephrotoxicity.

This record should be cited as:

Johansen HK, Gøtzsche PC. Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia. Cochrane Database of Systematic Reviews 2000, Issue 3. Art. No.: CD000969. DOI: 10.1002/14651858.CD000969

Assessed as up to date:

July 18, 2011

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Primary Review Group:

Gynaecological Cancer Group

Health topics:

Cancer > Generic cancer care > Infections in neutropenic patients

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Independent high-quality evidence for health care decision making

Prevention of fungal infections in patients with cancer with amphotericin B

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