In vitro activity of systemic antifungal agents against Malassezia furfur

Abstract

The activity of four antifungal agents against 15 systemic (blood and vascular catheter) and 10 superficial (skin) Malassezia furfur isolates was evaluated. MIC ranges were similar for the two groups of organisms: amphotericin B, 0.3 to 2.5 ,g/ml; flucytosine, >100 ,g/ml; miconazole, 0.4 to 1.5 ,utg/ml; and ketoconazole, 0.025 to 0.4 ,g/mi.Malassezia furfur is a lipid-dependent yeast commnonly found on the skin of adolescents and adults and the causative agent of tinea versicolor, a chronic, superficial skin infection (9). The organism has recently been isolated from the skin of neonates in intensive care nurseries and also from deep-line vascular catheters and catheter blood cultures in patients with signs and symptoms of sepsis (1,4,7,8). Adnministration of parenteral fat emulsions for caloric supplementation via a deep-line catheter is highly associated with subsequent catheter colonization and probable sepsis (4,7,8). However, M. furfur has not been recovered directly from fat emulsi6n fluids, and we hypothesize that catheter colonization and associated sepsis occur subsequent to skin colonization, while the fat emulsions provide the necessary lipid growth requirement for the organism. The organism has also been recovered from peripheral blood and lung tissue at biopsy and autopsy, suggesting the systemic nature of this infection (8). Although most patients have been successfully managed by removal of the infected catheter, vascular access is often critical, and treatment of patients with antifungal therapy while the catheter remains in place is an alternative form of management. (5) grew >15 CFU (most grew >100 CFU) of M. furfur; (iii) tnost patients had multiple positive catheter blood cultures collected over several days; (iv) the patients appeared septic, and laboratory data supported this observation (fever, apnea, bradycardia, thrombocytopeniaj leukocytosis, elevated neutrophil band counts); (v) patients responded dramatically to catheter removal; and (vi) no other infectious agent was recovered from blood or catheter tip culture. We previously reported the clinical presentation of five of these patients (7). Skin isolates were obtained from scrapings of the back or chest of infants hospitalized in an intensive care unit. Organisms Were isolated on glucose-yeast extract-peptone agar (GYP-S) supplemented with glycerol monostearate (0.25%), Tween 80 (0.2%), and olive oil (2%) (6). Isolates were subcultured once or twice on GYP-S, harvested after 2 or 3 days of growth at 35°C, and stored frozen at -70°C in whole sheep blood.

Use of Fatty Acid RPMI 1640 Media for Testing Susceptibilities of Eight Malassezia Species to the New Triazole Posaconazole and to Six Established Antifungal Agents by a Modified NCCLS M27-A2 Microdilution Method and Etest

“…Although terbinafine, amorolfine, and established and newer azole compounds have been tested against Malassezia skin isolates by BMD methods (4,12), data on the in vitro performance of amphotericin B are almost exclusively associated with cases of bloodstream infections (1,9,18). However, these studies were performed prior to the resolution of the taxonomic status of Malassezia species and the recognition of new species (5).…”

“…Regarding bloodstream Malassezia infections, poor response to amphotericin B has led to discontinuation of parenteral therapy as an additional therapeutic measure (18) or modification of therapy in order to increase the amphotericin B concentration in the catheter lumen, aiming at eradicating Malasssezia yeasts (1). However, the observed poor clinical response (10,18,19,21) has not been supported by in vitro data, as susceptibility of Malassezia furfur (sensu lato) to amphotericin B has been recorded (9). Apart from host and yeast factors responsible for the in vivo-in vitro difference in amphotericin B efficiency, the effect of medium composition on yeast growth and drug availability may have accounted for the observed discrepancies between laboratory and clinical findings.…”

A Modified Christensen's Urea and CLSI Broth Microdilution Method for Testing Susceptibilities of SixMalasseziaSpecies to Voriconazole, Itraconazole, and Ketoconazole

“…Earlier data were for either M. furfur or Pityrosporum spp. (1,6,7,14,18,19). Susceptibility to the three azoles was species dependent, with low MICs (Ͻ1 g/ml) for most Malassezia spp.…”

The Malassezia Genus in Skin and Systemic Diseases

“…As is evident in the cases described in Table 11, the rapid diagnosis and removal of the CVC can suffice for cure when the underlying condition is reversible. An alternative therapeutic approach that has been successfully used incorporates the reallocation of the infusion site to a peripheral vein (209). Malassezia sepsis is not very rare, as it was reported for up to 23% of sepsis cases (3 out of 13 patients) (152) in 263 infants prospectively studied in an ICU and in 2/66 (3%) (291) infants after the placement of a central venous catheter.…”

“…An autopsy reported evidence of small-vessel vasculitis with abundant monopolar budding yeast cells, identified as Malassezia after morphological study in a mycology laboratory. Since then, a plethora of publications describing Malassezia infections in premature and debilitated infants who were receiving total parenteral nutrition with lipid supplementation have been reported (Table 11) (7,17,124,175,203,209,235,251,252,283,333). As is evident in the cases described in Table 11, the rapid diagnosis and removal of the CVC can suffice for cure when the underlying condition is reversible.…”