Activity of aminocandin (IP960) compared with amphotericin B and fluconazole in a neutropenic murine model of disseminated infection caused by a fluconazole-resistant strain of Candida tropicalis

OBJECTIVES: To compare the activity of aminocandin (IP960), a new echinocandin with broad-spectrum in vitro activity against Aspergillus and Candida spp., with that of amphotericin B and fluconazole in a temporarily immunocompromised murine model of disseminated candidiasis. METHODS: Mice were rendered neutropenic with cyclophosphamide and infected intravenously 3 days later with a fluconazole-resistant Candida tropicalis strain. Mice were treated with intraperitoneal amphotericin B (5 mg/kg/dose), oral fluconazole (50 mg/kg/dose), intravenous aminocandin (0.1--5 mg/kg/dose) or solvent control for 9 days. Mice were observed for survival and survivors were sacrificed 11 days post-infection. Kidneys, liver, brain and lungs were removed for semi-quantitative culture. RESULTS: Control mice had 90--100% mortality. After infection with C. tropicalis, aminocandin 2.5 and 5 mg/kg/day and amphotericin B yielded 80% survival; aminocandin 1 mg/kg/day yielded 70% survival; aminocandin 0.25 and 0.1 mg/kg/day yielded 30% and 20% survival, respectively; and fluconazole 50 mg/kg/day and control regimens yielded 10% and 0--10% survival, respectively. Aminocandin 2.5 and 5.0 mg/kg/day and amphotericin B were superior in reducing mortality compared with aminocandin 0.25 and 0.1 mg/kg/day, fluconazole and controls (P<0.047). The only regimen to reduce organ burdens below detectable levels was amphotericin B, which cleared 40% of mice. All organ burdens in the aminocandin 1.0, 2.5 and 5.0 mg/kg/day and amphotericin B regimens were significantly lower than other groups (P<0.02). CONCLUSIONS: The data demonstrate that aminocandin at doses of >or=1.0 mg/kg/day is as effective as amphotericin B at improving survival and reducing organ burdens in this murine model of disseminated C. tropicalis.     

Comparison of fluconazole and amphotericin B for treatment of experimental Candida endocarditis caused by non-C. albicans strains.

Amphotericin B and fluconazole were compared for the treatment of experimental Candida endocarditis caused by Candida tropicalis and C. parapsilosis. Rabbits received no therapy, amphotericin B (1 mg/kg of body weight per day intravenously), or fluconazole (100 mg/kg/day intraperitoneally) for either 11 or 21 days. Against both species, amphotericin B and fluconazole were equally effective overall; however, amphotericin B was more rapidly fungicidal than fluconazole in vivo against C. tropicalis.     

In vivo activity of micafungin in a persistently neutropenic murine model of disseminated infection caused by Candida tropicalis

Micafungin is a new echinocandin with broad-spectrum in vitro and in vivo antifungal activity against both Aspergillus and Candida species. We compared the activity of micafungin with that of amphotericin B and fluconazole in a persistently immunocompromised murine model of disseminated candidiasis against a strain of Candida tropicalis that was resistant to amphotericin B and fluconazole in vitro. Mice were rendered persistently neutropenic with multiple doses of cyclophosphamide and infected intravenously with C. tropicalis. Mice were treated with either intraperitoneal amphotericin B (0.5-5 mg/kg per dose), oral fluconazole (50 mg/kg twice a day), intravenous micafungin (1-10 mg/kg per dose) or solvent control for 7 days. Mice were killed at 11 days post-infection and kidneys, lungs, brain and liver removed for quantitative culture. Overall mortality in the model was low, with rates varying between 10% and 25% in treatment groups. Micafungin at doses between 2 and 10 mg/kg were the only regimes able to reduce cfu below the level of detection of tissues infected with C. tropicalis. Micafungin was well tolerated by the mice and was much more effective than amphotericin B or fluconazole against an amphotericin B- and fluconazole-resistant C. tropicalis.     

In-vitro activity of cilofungin (LY121019) in comparison with amphotericin B

The in-vitro activity of cilofungin, a derivative of echinocandin B, was compared with that of amphotericin B in Sabouraud dextrose and Antibiotic Medium No. 3 against 100 clinical isolates of yeasts. Cilofungin appeared to be as effective, as amphotericin B against Candida albicans and yet more effective against Can. tropicalis as far as growth inhibition was concerned. Cilofungin was less active than amphotericin B against Can. (Torulopsis) glabrata and other species of Candida. It was not active against Cryptococcus neoformans. Minimum fungicidal concentrations (MFCs) of cilofungin were highly dependent on the medium, especially with Can. albicans. Low MFCs were observed in Antibiotic Medium 3 and very high MFCs were measured in Sabouraud's medium. Using a killing curve method, the initial rate of killing of amphotericin B was proportional to concentration with Can. albicans, Can. tropicalis, and Can. glabrata. With cilofungin the rate of killing was proportional to concentration only for Can. tropicalis.     

Synergy between cilofungin and amphotericin B in a murine model of candidiasis.

The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5) CFU of Candida albicans. At 4 days postinfection, intraperitoneal therapy was initiated and was continued for 14 days. Therapy groups included those given cilofungin at 6.25 or 62.5 mg/kg/day (given twice daily), amphotericin B at 0.625 mg/kg/day (given once daily), cilofungin at 6.25 mg/kg/day plus amphotericin B, and cilofungin at 62.5 mg/kg/day plus amphotericin B. Mice were observed through 30 days postinfection. All infected untreated mice died of infection between days 6 and 18. Eighty-five percent of mice receiving cilofungin at 6.25 mg/kg/day died between days 13 and 30. All other mice survived. Quantitative determination of the number of CFU of C. albicans in the spleens and kidneys of all survivors revealed that mice that had received both drugs had lower residual burdens of C. albicans. All mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B had sterile spleens, whereas 42 to 58% of mice given cilofungin or amphotericin B monotherapy had sterile spleens. All kidneys were infected in mice which had received cilofungin at 62.5 mg/kg/day or amphotericin B. Neither organ was infected in 17% of each group receiving combination therapy with cilofungin and amphotericin B. The number of CFU in the kidneys of mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B was lower than those cultured from mice treated with cilofungin at 62.5 mg/kg/day (P less than 0.001, Mann-Whitney) or amhotericin B (P less than 0.05). Modest synergy was noted in inhibition of the C. albicans isolate in vitro. Pharmacokinetic studies showed elevated levels of cilofungin but not amphotericin B in sera of mice treated with combined therapy compared with those in mice given monotherapy. No overt toxicity was evident with any regimen. The mechanism of increased efficacy may be altered cilofungin distribution, excretion, or metabolism; antifungal synergy; or both. These results indicate that concurrent cilofungin-amphotericin B therapy has synergistic or additive efficacy in vivo.     

Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice.

The efficacies of cilofungin (Ly121019), a semisynthetic lipopeptide antifungal agent, and amphotericin B in the treatment of disseminated candidiasis in normal and neutropenic mice were compared. In mice infected with 2 x 10(6) CFU of Candida albicans, treatment with cilofungin in twice-daily doses of 25 or 35 mg/kg of body weight by intraperitoneal injection for 10 days gave survival rates of 83 and 90%. In contrast, there was 97% mortality in infected controls receiving 2 x 10(6) CFU intravenously and 93% survival in mice treated with 1 mg of amphotericin B per kg once a day. Mice rendered granulocytopenic by the administration of cyclophosphamide showed survival rates of 83 and 80% when treated with 25 or 35 mg of cilofungin per kg for 10 days compared with 43% survival rate in mice treated with 1 mg of amphotericin B per kg (P = 0.0030 and P = 0.0080, respectively). Similar results were obtained when the two antifungal agents were administered for a period of 30 days. Administration of 25 or 35 mg of cilofungin per kg twice a day to granulocytopenic mice receiving 10(6) CFU of C. albicans gave survival rates of 93% and 93% compared with 53% survival with amphotericin B. With 15 mg of cilofungin per kg twice a day for 10 days, a survival rate of 43 to 50% was observed in both normal and granulocytopenic mice compared with 56 and 60%, respectively, when this dosage was continued for 30 days. Cilofungin eradicated C. albicans from the kidneys, spleens, and livers of surviving animals. No toxic effects were observed with any of the dosage regimens used. The clearance of C. albicans from the kidneys, spleens, livers, and brains in normal mice was studied following infection with 5 x 10(5) and 1 x 10(5) intravenously. The mice in the treatment groups received 25 mg of cilofungin per kg twice a day for 10 days. In 8 to 12 days, this treatment was able to clear the organisms from the kidneys, spleens, and livers of mice infected with 5 x 10(5) C. albicans. Mice infected with 10(5) C. albicans and treated with cilofungin (25 mg/kg) twice a day for 10 days had no organisms in the kidney, spleen, and liver at days 8, 2, and 8, respectively. There was 1-log-unit reduction in C. albicans counts in brain tissue from mice of one of the treated groups between 2 h and 2 days postinfection, after which the numbers of organisms remained the same until day 12. These data demonstrate the efficacy of cilofungin in the treatment of disseminated C. albicans infections in normal and granulocytopenic mice. The treatment regimen used in this study was able to clear C. albicans from the kidneys, spleen, and liver but not from brain tissue.     

Distribution and antifungal susceptibility of Candida species causing candidemia from 1996 to 1999

Susceptibilities to amphotericin B and fluconazole of 383 Candida species isolated from blood were determined. Candida albicans was the most common species (55.6%), followed by Candida parapsilosis (17.5%), Candida tropicalis (16.5%), Candida glabrata (5.2%), Candida guilliermondii (2.3%), and others (2.9%). All but three isolates, Candida ciferrii, C. tropicalis, and C. glabrata, one each, were susceptible to amphotericin B. A total of 367 (95.8%) and 15 (4.2%) isolates were susceptible and susceptible-dose dependent to fluconazole, respectively. Only one isolate, a C. glabrata, was resistant to fluconazole. Few patients (13%) having prior fluconazole treatments may explain the low rate of resistance to fluconazole in this study.     

In vivo activity of amphotericin B lipid complex in immunocompromised mice against fluconazole-resistant or fluconazole-susceptible Candida tropicalis

We compared four doses of amphotericin B lipid complex (ABLC) with three doses of fluconazole in temporarily neutropenic mice in a murine model of disseminated candidiasis due to four different isolates of Candida tropicalis. The mice were infected with a 90% lethal dose of four strains of C. tropicalis for which the fluconazole MICs ranged from 1 to >125 mg/liter 3 days after receiving 200 mg of cyclophosphamide/kg of body weight. Treatment was started 18 h after infection and lasted for 7 days. ABLC (1, 2, 5, and 10 mg/kg) was administered once a day intravenously, fluconazole was administered by oral gavage once daily (25 and 50 mg/kg/day) or twice daily (125 mg/kg). MICs determined in five different ways with 24- and 48-h endpoints were also compared. The overall survival rates were controls, 14%; fluconazole, 64%; and ABLC, 82%. Treatment with ABLC at 2 to 10 mg/kg increased survival compared to controls (P = <0.0001) and was also superior to fluconazole at 25 and 50 mg/kg (P = 0.006). In the fluconazole-resistant C. tropicalis model (MIC, 128 microg/ml), ABLC at 2 to 10 mg/kg was superior to fluconazole at 250 mg/kg and ABLC at 10 mg/kg was superior to all fluconazole doses (P = <0.05). Fluconazole at 250 mg/kg daily was superior to both 25 and 50 mg/kg at reducing mortality with most isolates. ABLC was superior to fluconazole (P = <0.01), and fluconazole at 250 mg/kg was superior to fluconazole at both 25 and 50 mg/kg (P = 0.02) in all models at reducing C. tropicalis counts in the kidneys. Neither drug consistently sterilized the brain or kidneys. A 48-h endpoint reading with the NCCLS susceptibility testing microtiter variation overestimates resistance to fluconazole. ABLC is an effective treatment for fluconazole-resistant C. tropicalis at all doses tested.     

Comparison of in vivo activity of fluconazole with that of amphotericin B against Candida tropicalis, Candida glabrata, and Candida krusei.

Fluconazole (UK-49,858) is a new oral bis-triazole antifungal agent with demonstrated activity against Candida albicans. Because of the increasing importance of infections due to other species of Candida, we studied the efficacy of fluconazole in a rat model of established systemic candidiasis, using clinical isolates of C. tropicalis, C. glabrata, and C. Krusei. In normal rats, oral fluconazole at both 20 and 80 mg/kg per day for 7 days reduced both kidney and liver titers of C. tropicalis and C. glabrata compared with those in control animals and was only slightly inferior to amphotericin B. Both fluconazole and amphotericin B were ineffective in reducing kidney titers of C. krusei, but amphotericin B was more effective than fluconazole in reducing liver titers. Fluconazole showed no increased efficacy at the higher dose of 80 mg/kg per day compared with 20 mg/kg per day in any experiment. These results suggest that oral fluconazole may be useful in the treatment of established disseminated candidiasis caused by species other than C. albicans. Further in vivo studies are needed, however, to define minimum effective doses and length of therapy and to test additional Candida isolates.     

In vitro susceptibility of 245 yeast isolates to amphotericin B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole.

The in vitro activity of amphotericin B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole was tested against 245 yeast strains isolated from clinical specimens (68 Candida albicans, 74 Candida tropicalis, 43 Candida krusei, 28 Candida glabrata, 19 Candida parapsilosis, 8 Candida lusitaniae and 5 Candida guilliermondii). An agar dilution method was employed to carry out testing. Minimal inhibitory concentrations to restrain 90% of isolate growth (MIC90) ranged from 0.12 to 2 mg/l for amphotericin B and for 5-fluorocytosine, from 0.03 to 8 mg/l for ketoconazole, from 0.05 to 50 mg/l for itraconazole and from 0.1 to > 100 mg/l for fluconazole. Among the azole derivatives, the most active was ketoconazole, followed by itraconazole. Only 1 strain of C. albicans was resistant to amphotericin B (MIC > 4 mg/l). Both C. tropicalis and C. krusei responded poorly to fluconazole and the former to itraconazole as well. The species most susceptible to the antifungal agents tested was C. glabrata and the most resistant were C. tropicalis and C. krusei.     

Fluconazole (UK-49,858) treatment of candidiasis in normal and diabetic rats.

Fluconazole (UK-49,858), a new oral bistriazole antifungal agent, was compared with amphotericin B in the treatment of established systemic infection with Candida albicans in normal and diabetic rats. In normal rats, oral fluconazole at 10 mg/kg per day for 7 days reduced Candida colony counts in the kidneys and livers as well as amphotericin B did and was nearly as effective as amphotericin B in a 21-day treatment trial. There was no further reduction in Candida colony counts when normal rats were treated with fluconazole at 40 mg/kg twice a day for 7 days. In streptozotocin-induced diabetic rats, fluconazole at 20 mg/kg per day for either 7 or 21 days compared favorably with amphotericin B in efficacy. Results of our study suggest that oral fluconazole may be useful in the treatment of established disseminated candidiasis in normal as well as diabetic hosts.     

抗真菌药物对院内真菌感染的应用分析

目的 了解住院患者深部真菌分离株对4种常用抗真菌药物的耐药状况.方法 采用ATB Expression真菌鉴定和药敏分析系统,对238株临床分离株进行菌种鉴定及耐药性检测.结果 对于192株白色念珠菌,氟康唑的最小抑菌浓度(MIC)≤0.25～64.00 mg/L,敏感162株(84.37%),中度敏感10株(5.20%),耐药20株(10.41%);5-氟胞嘧啶MIC≤0.50～32.00 mg/L,敏感185株(96.30%),中度敏感4株(2.08%),耐药3株(1.56%);两性霉素B MIC≤0.50～2.00 mg/L,全部敏感;伊曲康唑的MIC≤0.13～1.00 mg/L,敏感177株(92.18%),中度敏感6株(3.12%),耐药9株(4.68%).热带念珠菌和光滑念珠菌对5-氟康唑耐药率分别为14.3%和27.3%,对伊曲康唑的耐药率为7.14%和9.09%,其余检出菌株均对5-氟胞嘧啶和两性霉素B敏感.结论 及时合理地应用抗真菌药物是防治深部真菌感染的关键.     

Activity of cilofungin (LY121019) against Candida species in vitro

Cilofungin (LY121019) was compared with amphotericin B in vitro for its inhibitory and fungicidal activity against Candida species. In minimal inhibitory concentration (MIC) tests the two compounds showed comparable inhibitory activity against 31 isolates of C. albicans and C. tropicalis. However, cilofungin was by comparison only weakly active against 19 isolates representing the species C. glabrata, C. kefyr and C. krusei, and essentially inactive against 11 isolates representing C. guilliermondii and C. parapsilosis. The inhibitory activity of cilofungin, unlike that of amphotericin B, was reduced in medium containing serum. Relative inhibition factors (RIFs) for the two compounds confirmed the MIC data: RIFs of 85% and more were obtained in tests with species other than C. albicans and C. tropicalis: for the latter two species, RIFs were in the range 41-66%, indicating drug activity comparable to that of systematically active azole compounds. (RIFs for amphotericin B were less than 40% for all isolates.) Cilofungin was generally less fungicidal than amphotericin B, and it was only rarely fungicidal in tests done in medium containing serum. Because of its inhibitory action and its low toxicity, the compound may prove to be therapeutically useful in infections caused by the two most commonly encountered pathogenic Candida species.     

Susceptibilities to amphotericin B and fluconazole of Candida species in Taiwan Surveillance of Antimicrobial Resistance of Yeasts 2006

Susceptibilities to amphotericin B and fluconazole of 964 Candida isolates collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts in 2006 were determined. There were 419 (43.5%) Candida albicans, 246 (25.5%) Candida tropicalis, 211 (21.9%) Candida glabrata, 62 (6.4%) Candida parapsilosis, 14 (1.5%) Candida krusei, and 12 (1.2%) others. Interestingly, 16 of the 17 amphotericin B-resistant isolates were non-albicans Candida species. The resistant rate to amphotericin B has decreased from 2.5% in 2002 to 1.8% in 2006. On the other hand, there were 132 C. tropicalis, 14 C. krusei, 10 C. albicans, and 9 C. glabrata isolates that had MICs to fluconazole > or =64 microg/mL. The prevalence of isolates with such high MICs was significantly higher than that in 2002 (17.1% versus 1.9%). Our results further indicate that most of the isolates with MICs to fluconazole > or =64 microg/mL exhibited the "trailing" phenomenon.     

In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole.

The in-vitro susceptibilities of 120 clinical isolates of yeasts to liposomal nystatin were compared with those to amphotericin B lipid complex (ABLC), liposomal amphotericin B (LAB), amphotericin B cholesteryl sulphate (ABCD), amphotericin B desoxycholate, nystatin, fluconazole and itraconazole. Yeast isolates examined included strains of Candida albicans, Candida parapsilosis, Candida glabrata, Candida krusei, Candida guilliermondii, Candida tropicalis, Candida kefyr, Candida viswanathii, Candida famata, Candida rugosa, Rhodotorula rubra, Trichosporon spp., Cryptococcus laurentii and Cryptococcus neoformans. The mean MICs for all strains examined were: liposomal nystatin 0.96 mg/L; nystatin 0.54 mg/L; ABLC 0.65 mg/L; LAB 1.07 mg/L; ABCD 0.75 mg/L; amphotericin B 0.43 mg/L; fluconazole 5.53 mg/L; and itraconazole 0.33 mg/L. No significant differences were seen between the activity of liposomal nystatin and the polyene drugs or itraconazole, but liposomal nystatin was more active than fluconazole. MICs were lower than the reported blood concentrations following therapeutic doses of this drug, indicating the potential for a therapeutic use of liposomal nystatin in humans. These results indicate good activity in vitro against medically important yeasts, which compares favourably with the activities of other currently available antifungal drugs. Liposomal nystatin may have a role in the treatment of disseminated and systemic mycoses.     

Susceptibilities to amphotericin B and fluconazole of Candida species in TSARY 2002

Susceptibilities to amphotericin B and fluconazole of 909 Candida species collected during the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 2002 were determined by the broth microdilution method. There were 395 (43.5%) Candida albicans, 244 (26.8%) C. tropicalis, 187 (20.6%) C. glabrata, 63 (6.9%) C. parapsilosis, 9 (1%) C. krusei, and 11 (1.2%) others. Among them, 23 (2.5%) isolates were resistant to amphotericin B. They consisted of 10 C. glabrata, 6 C. krusei, 3 C. albicans, 1 C. tropicalis, 1 C. parapsilosis, and 2 others. The resistance rate to amphotericin B has increased compared with that of TSARY 1999 (2.5% versus 0.5%). There were 7 C. krusei, 5 C. albicans, 3 C. glabrata, and 2 others isolates resistant to fluconazole. The resistance rate to fluconazole has decreased from 8.4% in 1999 to 1.9% in 2002. A pattern of coresistance to both amphotericin B and fluconazole was observed.     

Antifungal susceptibility of Candida spp. isolated from pediatric patients: a survey of 4 children's hospitals

Candida species are the most common cause of fungal infections in hospitalized patients. Recent studies have reported a relative reduction in the rates of infection caused by Candida albicans and a shift toward non-albicans Candida spp. Data on the distribution and susceptibility of Candida spp. from children's hospitals are limited. Clinical isolates of Candida were collected from 4 US children's hospitals in 2003. Broth dilution MICs for amphotericin B, fluconazole, voriconazole, caspofungin, posaconazole, and ravuconazole were performed according to National Committee for Clinical Laboratory Standards-approved methodology. A total of 179 clinical isolates were identified and included. Of 179, 77 (43%) were C. albicans. Candida parapsilosis isolates were the second most frequently identified (57/175, 32%), followed by Candida glabrata, Candida tropicalis, and Candida lusitaniae (approximately 8% each). Caspofungin was the most active agent in vitro against all Candida spp. Fluconazole resistance was seen among C. glabrata, C. tropicalis, and Candida krusei isolates. Newer azoles had improved activity against fluconazole-resistant isolates of Candida. Among isolates of C. parapsilosis, nearly 20% were resistant to amphotericin B. The current study highlights the emergence of C. parapsilosis as a distinct pediatric pathogen with clinical and therapeutic implications. Furthermore, our current susceptibility data include newer antifungal agents that appear to be quite active in vitro and may provide new therapeutic options for the treatment of serious yeast infections in children.     

SCH 51048, a new antifungal triazole active against hematogenous Candida krusei infections in neutropenic mice.

Candida krusei is increasingly recognized as an opportunistic pathogen in immunocompromised patients and is inherently resistant to fluconazole. We tested the in vivo efficacy of SCH 51048, an investigational antifungal triazole, in experimental hematogenous murine infection caused by two C. krusei isolates and compared its activity with those of amphotericin B and fluconazole. CF1 mice were immunosuppressed with cyclophosphamide and cortisone acetate and were challenged intravenously with infecting inocula of each C. krusei isolate. Treatment with SCH 51048 (50 or 100 mg/kg of body weight per day orally) or amphotericin B (2 mg/kg/day intraperitoneally) significantly prolonged the survival of infected mice and significantly reduced fungal titers in the kidneys (P < or = 0.05). Treatment with fluconazole (100 mg/kg/day orally) had no effect. Both dosages of SCH 51048 were as effective as amphotericin B in improving survival, but the higher dosage was significantly (P < or = 0.05) better in reducing the fungal burden in the kidneys of infected animals. A dose-dependent response was observed with SCH 51048 treatment, especially in organ clearance. Our results indicate that SCH 51048 is the first triazole that has in vivo activity against experimental infection with C. krusei and deserves further evaluation.     

Efficacy of cilofungin alone and in combination with amphotericin B in a murine model of disseminated aspergillosis.

Cilofungin, amphotericin B, and a combination of the two drugs were compared in a model of aspergillosis in immunocompetent mice in three experiments. Cilofungin was equivalent to amphotericin B in preventing death and eradicating cerebral aspergillosis, but it did not sterilize the kidneys. This is the first demonstration of the in vivo activity of cilofungin against any fungus other than Candida albicans. The mortality with combination therapy was higher than those with amphotericin B alone (P = 0.003) and cilofungin alone (P = 0.054), as was weight loss after infection, indicating antagonism between cilofungin and amphotericin B in this model. The mechanisms of action and antagonism remain to be explained.     

Antifungal susceptibilities of clinical isolates of Candida species, Cryptococcus neoformans, and Aspergillus species from Taiwan: surveillance of multicenter antimicrobial resistance in Taiwan program data from 2003

The susceptibilities of nonduplicate isolates to six antifungal agents were determined for 391 blood isolates of seven Candida species, 70 clinical isolates (from blood or cerebrospinal fluid) of Cryptococcus neoformans, and 96 clinical isolates of four Aspergillus species, which were collected in seven different hospitals in Taiwan (as part of the 2003 program of the study group Surveillance of Multicenter Antimicrobial Resistance in Taiwan). All isolates of Candida species other than C. glabrata and C. krusei were susceptible to fluconazole. Among the 59 C. glabrata isolates, 16 (27%) were not susceptible to fluconazole, and all were dose-dependently susceptible or resistant to itraconazole. For three (5.1%) C. glabrata isolates, voriconazole MICs were 2 to 4 microg/ml, and for all other Candida species isolates, voriconazole MICs were /=2 microg/ml were 100% (3 isolates) for C. krusei, 11% (23 of 207 isolates) for Candida albicans, 3.0% (2 of 67 isolates) for Candida tropicalis, 20% (12 of 59 isolates) for C. glabrata, and 0% for both Candida parapsilosis and Candida lusitaniae. For three (4%) Cryptococcus neoformans isolates, fluconazole MICs were >/=16 microg/ml, and two (3%) isolates were not inhibited by 1 mug of amphotericin B/ml. For four (4.2%) of the Aspergillus isolates, itraconazole MICs were 8 microg/ml. Aspergillus flavus was less susceptible to amphotericin B, with the MICs at which 50% (1 microg/ml) and 90% (2 microg/ml) nsrsid417869\delrsid7301351 of isolates were inhibited being twofold greater than those for Aspergillus fumigatus and Aspergillus niger. All Aspergillus isolates were inhibited by 相似文献