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Many patients in an ICU are intestinal carriers of yeasts with an inherent risk of infections if bowel perforation occurs. Resistance to azoles is increasing, while treatment with conventional amphotericin B (AM-B) is associated with potential toxicity. AM-B given in a continuous 24-hour infusion may be less toxic compared with the conventional 4-hour to 6-hour infusion rate of AM-B [1,2]. AM-B given in a continuous 24-hour infusion is only evaluated in a tertiary care setting, with a predominance of immunocompromised patients. We evaluated the feasibility and safety of continuous AM-B treatment in critically patients with suspected or proven yeast or fungal infections.
This is an observational retrospective analysis for the side effects in consecutive patients treated with AM-B from January 2003 to December 2008 in our ICU department. During the investigation period patients received amphotericin B: 40 mg/24 hours or a lower dose if the MDRD clearance was less than 60 ml/min. During the treatment the dose was adjusted to the desired therapeutic range of 200 to 1,000 μg/l according to measured plasma levels.
The mean treatment duration was 12.3 ± 6.3 days with a dose of 32.1 ± 12.2 mg/24 hours. Of the 10 patients who died, seven died after the termination of the AM-B therapy, without signs of an active yeast or fungal infection. Within the first week three patients died, necropsy was carried out in one case, demonstrating a PCP infection, and in two patients a role of antibiotic failure cannot be ruled out. All other patients with proven yeast or fungal infection demonstrated a clinical recovery of their infection. The AM-B concentration was measured in 113 blood samples, nine samples had a level <200 μg/l and 10 a level >1000 μg/l. Renal impairment, defined as more than 1.5 times the creatinine at the start of the treatment with AM-B, occurred in 9% and was not evaluable in 6% due to unresolving renal replacement therapy dependency at the start of AM-B. None of the evaluated patients developed a creatinine more than 2.0 times the baseline value. Temporary elevation of liver enzymes was seen in 23%, without the need for dose modification. Hypokalemia (K+ <3.0 mmol/l) was observed in one patient.
Compared with the conventional infusion rate of AM-B, we conclude that continuous 24-hour infusion seems a feasible and safer treatment alternative in patients with invasive yeast or fungal infections.