Therapeutic efficacy of posaconazole against isolates of Candida albicans with different susceptibilities to fluconazole in a vaginal model.

A battery of 34 vaginal isolates of Candida albicans was tested against posaconazole (POS) and fluconazole (FLU) to determine their in vitro susceptibilities and to obtain FLU-susceptible and FLU-resistant strains for the murine in vivo studies. FLU-resistant strains were chosen on the basis of their 48-h MICs. The 48-h geometric mean MICs for all isolates tested were 0.016 and 0.656 microg/ml for POS and FLU, respectively. The treatment regimens for the vaginal murine infection model were POS or FLU at 10 or 20 mg/kg of body weight/day and 20 mg/kg twice a day. All regimens with POS were effective in reducing fungal burden of both the fluconazole-susceptible and resistant isolates of C. albicans. All FLU regimens were effective against infection induced by the fluconazole-susceptible strain. While FLU at 10 mg/kg was ineffective against fungal burden of the resistant strain, treatment with FLU at 20 mg/kg once or twice a day was effective against this strain. Both POS and FLU at 20 mg/kg twice a day were able to clear C. albicans from vaginas of mice infected with the fluconazole-susceptible strain. POS displayed a more effective in vivo activity than FLU in the treatment of murine C. albicans vaginitis produced by isolates with different susceptibilities to FLU.     

Correlation between in vitro and in vivo antifungal activities in experimental fluconazole-resistant oropharyngeal and esophageal candidiasis

Oropharyngeal and esophageal candidiasis (OPEC) is a frequent opportunistic mycosis in immunocompromised patients. Azole-resistant OPEC is a refractory form of this infection occurring particularly in human immunodeficiency virus (HIV)-infected patients. The procedures developed by the Antifungal Subcommittee of the National Committee for Clinical Laboratory Standards (NCCLS) are an important advance in standardization of in vitro antifungal susceptibility methodology. In order to further understand the relationship between NCCLS methodology and antifungal therapeutic response, we studied the potential correlation between in vitro susceptibility to fluconazole and in vivo response in a rabbit model of fluconazole-resistant OPEC. MICs of fluconazole were determined by NCCLS methods. Three fluconazole-susceptible (FS) (MIC, /=64 microgram/ml) isolates of Candida albicans from prospectively monitored HIV-infected children with OPEC were studied. FR isolates were recovered from children with severe OPEC refractory to fluconazole, and FS isolates were recovered from those with mucosal candidiasis responsive to fluconazole. Fluconazole at 2 mg/kg of body weight/day was administered to infected animals for 7 days. The concentrations of fluconazole in plasma were maintained above the MICs for FS isolates throughout the dosing interval. Fluconazole concentrations in the esophagus were greater than or equal to those in plasma. Rabbits infected with FS isolates and treated with fluconazole had significant reductions in oral mucosal quantitative cultures (P < 0.001) and tissue burden of C. albicans in tongue, soft palate, and esophagus (P < 0.001). In comparison, rabbits infected with FR isolates were unresponsive to fluconazole and had no reduction in oral mucosal quantitative cultures or tissue burden of C. albicans versus untreated controls. We conclude that there is a strong correlation between in vitro fluconazole susceptibility by NCCLS methods and in vivo response to fluconazole therapy of OPEC due to C. albicans.     

Activities of micafungin against 315 invasive clinical isolates of fluconazole-resistant Candida spp

Micafungin is a new echinocandin exhibiting broad-spectrum activity against Candida spp. The activity of the echinocandins against Candida species known to express intrinsic or acquired resistance to fluconazole is of interest. We determined the MICs of micafungin and caspofungin against 315 invasive clinical (bloodstream and other sterile-site) isolates of fluconazole-resistant Candida species obtained from geographically diverse medical centers between 2001 and 2004. MICs were determined using broth microdilution according to the CLSI reference method M27-A2. RPMI 1640 was used as the test medium, and we used the MIC endpoint of prominent growth reduction at 24 h. Among the 315 fluconazole-resistant Candida isolates, 146 (46%) were C. krusei, 110 (35%) were C. glabrata, 41 (13%) were C. albicans, and 18 (6%) were less frequently isolated species. Micafungin had good in vitro activity against all fluconazole-resistant Candida spp. tested; the MICs at which 50% (MIC(50)) and 90% (MIC(90)) of isolates were inhibited were 0.03 microg/ml and 0.06 microg/ml, respectively. All the fluconazole-resistant Candida spp. were inhibited at a micafungin MIC that was 相似文献   

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

Ibuprofen, a non-steroidal anti-inflammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg/ml, ibuprofen showed a rapid cidal activity against exponential growth phase C. albicans, accompanied by rapid and extensive leakage of intracellular K+, permeation to propidium iodide, lysis of spheroplasts and severe membrane ultrastructural alterations. These results indicate that the killing of Candida cells is due to direct damage to the cytoplasmic membrane. At 5 mg/ml, ibuprofen inhibited growth; however, it did not kill the yeasts and did not directly affect the cytoplasmic membrane. Evaluation of yeast metabolic vitality with the fluorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. The combination of ibuprofen with fluconazole resulted in synergic activity with eight of the 12 Candida strains studied, including four of the five fluconazole-resistant strains. The MICs of fluconazole for the fluconazole-resistant strains decreased 2-128-fold when the drug was associated with ibuprofen. When in combination with fluconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the practicability of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties.     

In vitro and in vivo antifungal activities of FX0685, a novel triazole antifungal agent with potent activity against fluconazole-resistant Candida albicans.

To evaluate the therapeutic potential of FX0685, a new triazole antifungal agent, for the treatment of opportunistic fungal infections, particularly systemic candidiasis and aspergillosis, in vitro and in vivo studies were performed using fluconazole (FLC), itraconazole (ITC) and/or amphotericin B (AMB) as reference drugs. A preliminary in vitro study showed that the antifungal activity of FX0685 against FLC-susceptible Candida albicans, several non-C. albicans Candida species and Cryptococcus neoformans was superior to that of FLC and comparable or superior to those of ITC and AMB, while the anti-Aspergillus fumigatus activity of FX0685 was to varying degrees lower than that of ITC. FX0685 appeared to be comparable to FLC and ITC in the treatment of murine systemic C. albicans and pulmonary A. fumigatus infection, respectively. The biological property of FX0685 was characterized by its potent in vitro and in vivo activity against FLC-resistant C. albicans. Part of this unique property was explained by the finding that it retained potent inhibitory activity against those CYP51 molecules in which amino acid substitutions confer a phenotype of resistance to FLC and some other azole derivatives. All of these results lead to the possibility that FX0685 may be a potential antifungal drug candidate for the treatment of various clinical forms of systemic candidiasis, including those caused by FLC-resistant C. albicans, as well as for the treatment of pulmonary aspergillosis.     

Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection.

After repeated use of fluconazole for therapy of oropharyngeal candidosis, the emergence of in vitro fluconazole-resistant Candida albicans isolates (MIC, > or = 25 micrograms/ml) together with oral candidosis unresponsive to oral dosages of up to 400 mg of fluconazole were observed in patients with human immunodeficiency virus (HIV) infection. Antifungal susceptibility testing was done by broth microdilution and agar dilution techniques on C. albicans isolates recovered from a cohort of patients with symptomatic HIV infection who were treated repeatedly with fluconazole for oropharyngeal candidosis. In vitro findings did show a gradual increase in the MICs for C. albicans isolates recovered from selected patients with repeated episodes of oropharyngeal candidosis. Primary resistance of C. albicans to fluconazole was not seen. Cross-resistance in vitro occurred between fluconazole and other azoles (ketoconazole, itraconazole), but to a lesser extent. The results of the study suggest that the development of clinical resistance to fluconazole could be clearly correlated to in vitro resistance to fluconazole. Itraconazole may still serve as an effective antifungal agent in patients with HIV infection and oropharyngeal candidosis nonresponsive to fluconazole.     

In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole

Anidulafungin is an echinocandin antifungal agent with potent activity against Candida spp. We assessed the in vitro activity of anidulafungin against 2,235 clinical isolates of Candida spp. using the CLSI broth microdilution method. Anidulafungin was very active against Candida spp. (the MIC at which 90% of strains are inhibited [MIC(90)] was 2 microg/ml when MIC endpoint criteria of partial inhibition [MIC-2] were used). Candida albicans, C. glabrata, C. tropicalis, C. krusei, and C. kefyr were the most susceptible species of Candida (MIC(90), 0.06 to 0.12 microg/ml), and C. parapsilosis, C. lusitaniae, and C. guilliermondii were the least susceptible (MIC(90), 0.5 to 2 microg/ml). In addition, 315 fluconazole-resistant isolates were tested, and 99% were inhibited by < or =1 microg/ml of anidulafungin. These results provide further evidence for the spectrum and potency of anidulafungin activity against a large and geographically diverse collection of clinically important isolates of Candida spp.     

In vitro susceptibilities of clinical isolates of Candida species, Cryptococcus neoformans, and Aspergillus species to itraconazole: global survey of 9,359 isolates tested by clinical and laboratory standards institute broth microdilution methods

The in vitro activity of itraconazole was determined against 7,299 isolates of Candida spp., 1,615 isolates of Cryptococcus neoformans, and 445 isolates of Aspergillus spp. obtained from over 200 medical centers worldwide. Itraconazole was active against all Candida spp. (96% of MICs were < or =1 microg/ml) with the exception of C. glabrata (77% of MICs were < or =1 microg/ml). Itraconazole inhibited 94% of C. krusei and 84% of other fluconazole-resistant Candida species, exclusive of C. glabrata, at a MIC of < or =1 microg/ml. Itraconazole was not active against fluconazole-resistant isolates of C. glabrata. Only modest activity was seen against C. neoformans (80% of MICs were < or =1 microg/ml); however, itraconazole showed excellent activity against Aspergillus spp. (94% of MICs were < or =1 microg/ml). These results provide an update on the antifungal activity of itraconazole against major opportunistic fungal pathogens. In light of the new intravenous formulation of itraconazole these data suggest that this agent remains a viable systemically active antifungal agent.     

Influence of berberine on T-cell mediated immunity

The protoberberine alkaloid berberine is isolated as a main alkaloid from the roots and bark of Berberis vulgaris. Berberine strongly inhibited in vitro the proliferative response of mouse spleen cells to T-dependent mitogens concanavalin A (Con A) and phytochemagglutinin (PHA). Spleen cells obtained from berberine-treated mice (10 mg/kg/3 days) expressed enhanced proliferative response to both mitogens. Berberine was applied to mice at different intervals before or after the induction of adjuvant arthritis (AIA) and Candida albicans (C. albicans) infection. The application of the alkaloid to new born mice (5 days after birth at a dose of 5 mg/kg/3 days) did not change the course of AIA and C. albicans infection. Its application at three 10 day intervals (5 mg/kg), starting from the 5 day after birth increased the joint inflammation in AIA. The host resistance to C. albicans infection was not affected, while the delayed type hypersensitivity (DTH)-reaction against the pathogen was enhanced. The alkaloid inhibited the development of AIA when applied after its onset (10 mg/kg from day ±3 to ±12 day). Berberine treatment during the ongoing infection did not influence its outcome (from ±2 to ±10 day).     

Antifungal activity of salaceyin A against Colletotrichum orbiculare and Phytophthora capsici

The antifungal activities of novel salicylic acid derivatives, salaceyin A, 6-(9-methyldecyl) salicylic acid, and salaceyin B, 6-(9-methylundecyl) salicylic acid were evaluated against plant pathogenic fungi. Salaceyin A showed antifungal activity against Cladosporium cucumerinum, Colletotrichum orbiculare and Phytophthora capsici at 64 microg ml(-1) while salaceyin B was less effective. In vitro antifungal activities of the compounds were influenced by the experimental pH value of the MIC test medium wherein their antifungal activities were enhanced by increasingly acidic conditions. Salaceyin A showed potent in vivo control efficacy against Phytophthora blight in pepper plants. The disease was effectively suppressed at 500 microg ml(-1), which was comparable to the commercial fungicide, metalaxyl. Salaceyin A suppressed anthracnose development on cucumber leaves in a concentration dependent manner. The control efficacy of salaceyin A against C. orbiculare infection was similar to chlorothalonil when applied prior to pathogen inoculation. Since the salaceyins are derivatives of salicylic acid, a known important signal molecule critical to plant defenses against pathogen invasion, we investigated the possibility that exogenous application of the salaceyin A would activate a systemic acquired resistance against P. capsici infection and C. orbiculare development on pepper and cucumber plants respectively. The addition of 500 microg ml(-1) of salaceyin A to the plant root systems did not significantly decrease disease development in the hosts. We are led to conclude that the disease control efficacy of salaceyin A against the Phytophthora blight and anthracnose diseases, mainly originates from the direct interaction of the agent with the pathogens.     

Influence of the immunostimulating substance tiprotimod on Candida albicans infection in relation to activation of macrophages

In an experimental model of persistent systemic candidiasis the effect of the thiazole compound Tiprotimod was examined. Balb/c mice infected intravenously with Candida albicans developed a fungal colonization of the kidneys with peak levels of about 10(6) colony forming units (cfu)/organ after 3 weeks of infection paralleled by the formation of necrotic alterations of the organs. Infected animals were treated with the immunostimulator Tiprotimod after the fungal colonization of kidney was manifested (3 days post infection). The treatment resulted in a decrease of the infectious load, abscess formation in kidney, as well as a reduction of Candida in the urine. The optimal dose in this model was in the range of 2 mg/kg, higher and lower doses appeared to be less effective, thus indicating a bell-shaped curve of response. By examining the time course of induction of protection by the drug it was noticed that protection does not occur before 10 days after infection. We therefore examined during the course of infection the phagocytic capacity and the production of O2- -radicals (chemiluminescence) of macrophages in Tiprotimod-treated animals. Activation of O2- -radical generation was stimulated rapidly (peak level at day 6) in the drug-treated animals, whereas stimulation of the phagocytic capacity was not observed until two weeks after infection. Activation of macrophage phagocytosis thus paralleled the reduction of the infectious load by Tiprotimod. Combination therapy with the antifungal agent ketoconazole resulted in at least additive decrease of mortality resulting from C. albicans infection.     

Cross-resistance between fluconazole and ravuconazole and the use of fluconazole as a surrogate marker to predict susceptibility and resistance to ravuconazole among 12,796 clinical isolates of Candida spp

Cross-resistance within a class of antimicrobial agents is a problem that is often encountered with antibacterial agents, and it is also an issue with antifungal agents. A current example is ravuconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. The present study addresses the issue of cross-resistance between fluconazole and ravuconazole and the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp. to ravuconazole. Reference broth microdilution MIC results for 12,796 strains of Candida spp. isolated from more than 200 medical centers worldwide were used. Ravuconazole MICs and tentative interpretive categories (susceptible, /=2 microg/ml) were compared with those of fluconazole by using regression statistics and error rate bounding analyses. For all 12,796 isolates, the absolute categorical agreement rate was 92.5% (rate of false-susceptible results, or very major errors [VME], 0.1%). Ravuconazole was active (MIC, 相似文献   

Variations in fluconazole susceptibility and DNA subtyping of multiple Candida albicans colonies from patients with AIDS and oral candidiasis suffering one or more episodes of infection.

Five Candida albicans colonies from each infection in AIDS patients receiving fluconazole therapy for oropharyngeal candidiasis over a 2-year period were evaluated by antifungal susceptibility testing and DNA subtyping, and the results were correlated with clinical response to determine the occurrence of clinically significant selection of more-resistant C. albicans over multiple infections. A total of 534 C. albicans isolates were obtained from 38 patients who exhibited 84 episodes of infection. Antifungal susceptibility testing revealed that the MICs for 93% of the isolates were < or = 8.0 microg/ml and the MICs for 7% of the isolates were > or = 64 microg/ml. DNA subtyping revealed 70 different subtypes, with 78% of patients with one infection exhibiting one DNA subtype and 80% of patients with more than one infection exhibiting multiple DNA subtypes. Also, patients who had multiple infections had lower CD4 counts than those with single infections. Differences between the single-infection group and the multiple-infection group regarding the number of DNA subtypes and CD4 counts were both statistically significant. Of the 74 evaluable infections all were successfully treated with regular-dose (100-mg/day) fluconazole, except for three patients who ultimately responded to higher-dose fluconazole. Only one patient may have shown clinically significant selection of a more-resistant C. albicans strain over multiple courses of treatment. Interestingly, MICs reached only 8.0 microg/ml, even though doses of 400 mg of fluconazole were necessary for clinical cure.     

Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector.

We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains.     

International and multicenter comparison of EUCAST and CLSI M27-A2 broth microdilution methods for testing susceptibilities of Candida spp. to fluconazole, itraconazole, posaconazole, and voriconazole

The aim of this study was to compare MICs of fluconazole, itraconazole, posaconazole, and voriconazole obtained by the European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI (formerly NCCLS) methods in each of six centers for 15 Candida albicans (5 fluconazole-resistant and 4 susceptible-dose-dependent [S-DD] isolates), 10 C. dubliniensis, 7 C. glabrata (2 fluconazole-resistant isolates), 5 C. guilliermondii (2 fluconazole-resistant isolates), 10 C. krusei, 9 C. lusitaniae, 10 C. parapsilosis, and 5 C. tropicalis (1 fluconazole-resistant isolate) isolates. CLSI MICs were obtained visually at 24 and 48 h and spectrophotometric EUCAST MICs at 24 h. The agreement (within a 3-dilution range) between the methods was species, drug, and incubation time dependent and due to lower EUCAST than CLSI MICs: overall, 94 to 95% with fluconazole and voriconazole and 90 to 91% with posaconazole and itraconazole when EUCAST MICs were compared against 24-h CLSI results. The agreement was lower (85 to 94%) against 48-h CLSI endpoints. The overall interlaboratory reproducibility by each method was > or =92%. When the comparison was based on CLSI breakpoint categorization, the agreement was 68 to 76% for three of the four species that included fluconazole-resistant and S-DD isolates; 9% very major discrepancies (< or =8 microg/ml versus > or =64 microg/ml) were observed among fluconazole-resistant isolates and 50% with voriconazole (< or =1 microg/ml versus > or =4 microg/ml). Similar results were observed with itraconazole for seven of the eight species evaluated (28 to 77% categorical agreement). Posaconazole EUCAST MICs were also substantially lower than CLSI MIC modes (0.008 to 1 microg/ml versus 1 to > or =8 microg/ml) for some of these isolates. Therefore, the CLSI breakpoints should not be used to interpret EUCAST MIC data.     

In vitro activities of posaconazole, ravuconazole, terbinafine, itraconazole and fluconazole against dermatophyte, yeast and non-dermatophyte species.

The in vitro activities of two new triazole antifungal agents with broad-spectrum antifungal activity, posaconazole and ravuconazole, were compared with those of three well-established antifungal agents, terbinafine, itraconazole and fluconazole, against 184 clinical isolates. These included 129 dermatophyte isolates (twelve species), 25 yeast isolates (five species) and 28 non-dermatophyte isolates (nine species). In vitro testing was conducted using microdilution plates with RPMI 1640 and National Committee for Clinical Laboratory Standards (NCCLS) guidelines (M27-38P) were followed, except for the preparation of the dermatophyte inoculum. Both posaconazole and ravuconazole showed similar broad-spectrum activity against dermatophyte, yeast and non-dermatophyte species. Mean inhibitory concentrations (MIC) at which 90% [MIC90] of the isolates were inhibited by posaconazole and ravuconazole were 0.25 and 0.5 microg/ml for dermatophytes, 0.5 and 0.25 microg/ml for yeasts, and >4 and 8 microg/ml for non-dermatophytes. The MIC ranges against Trichophyton (six species), Microsporum (five species) and Epidermophyton flocossum were: posaconazole (0.007-1.0/0.007-0.25/0.007-1.0 microg/ml), ravuconazole (0.015-8.0/0.015-1.0/0.015-1.0 microg/ml), itraconazole (0.015- >8.0/0.015-0.5/ 0.015-8.0 microg/ml), fluconazole (0.125- >64.0/4.0 >64.0/0.5-64.0 microg/ml) and terbinafine (0.003 >2.0/0.007-2.0/0.007 >2.0 microg/ml). Overall ranking of the antifungal activity of the five antifungal agents was: terbinafine > posaconazole > ravuconazole > itraconazole > fluconazole, for dermatophytes; ravuconazole > posaconazole > itraconazole > fluconazole > terbinafine, against yeasts; and posaconazole > ravuconazole > terbinafine > itraconazole > fluconazole, for non-dermatophytes.     

The effect of an Aspergillus fumigatus derived elastolytic proteinase on human neutrophils.

The effect of elastolytic proteinase on quantitative nitroblue tetrazolium (NBT) dye reduction and chemotaxis of human neutrophil was examined. Elastolytic proteinase is derived from Aspergillus fumigatus 9409. NBT dye reduction was inhibited significantly by 133microEg/ml of elastolytic proteinase (p<0.05). Chemotaxis was also inhibited significantly by 400microEg/ml of the enzyme, compared to the control group (p<0.05). These findings suggest that elastolytic proteinase, depending on its concentration, acts as an inhibitory agent to both NBT dye reduction and chemotaxis activities in the human neutrophil. The findings that this enzyme suppressed neutrophil function in A. fumigatus infection is of importance, because it is now suspected that the enzyme has the potential to cause infection.     

Antifungal activity of splenic, liver and pulmonary macrophages against Candida albicans and effects of macrophage colony-stimulating factor.

Disseminated infections due to Candida albicans are frequently encountered in immunocompromised patients. We compared the antifungal activities of macrophages residing in spleen, liver and lungs of rabbits against blastoconidia and pseudohyphae of C. albicans. Splenic adherent cells (SAC), Kupffer cells (KC) and pulmonary alveolar macrophages (PAM) all ingested blastoconidia efficiently. SAC caused significantly more damage to unopsonized pseudohyphae compared with KC (P < 0.01) or PAM (P < 0.001). Incubation of SAC with 15 ng ml(-1) of recombinant human macrophage colony-stimulating factor (M-CSF) at 37 degrees C for 2 days significantly enhanced phagocytosis (P = 0.02) and killing (P = 0.05) of blastoconidia. In contrast, M-CSF had no effect on phagocytic activities of KC or PAM against blastoconidia or on damage caused by any of the macrophages to pseudohyphae of C. albicans. Thus, although all three resident macrophage types ingest blastoconidia efficiently, they differ in their capacity to cause damage to pseudohyphae and in their responsiveness to M-CSF for antifungal activation. M-CSF augments the capacity of SAC to ingest and kill blastoconidia and may therefore have a role in the treatment and prevention of hematogenously disseminated candidiasis.     

Prophylaxis Against Fungal Infections in Transplant Recipients: Possible Approaches

Although the morbidity and mortality associated with invasive fungal infections in transplant recipients is high, the optimal approach to antifungal prophylaxis is controversial. Most fungal infections occur shortly after the trans- plantation during maximum immunosuppression and are caused by Candida or Aspergillus spp. Nonspecific strategies for prevention do not differ from those used in other patients at risk. They consist mainly of a reduction in risk factors, such as removal of plants from around the patient, separation of the patient from the vicinity of construction sites or improvement in hospital care by isolation and careful nursing of the patient, with strict hygiene. A more controversial issue is primary antifungal chemoprophylaxis, since there are few well designed trials of this intervention, and most of the patients studied have had haematological diseases. Orally administered antifungal drugs that are not absorbed through the gastrointestinal tract have not shown any evidence of a prophylactic effect to date. Controlled trials of systemically administered or orally absorbed drugs in specific transplant recipients have, however, proved effective. In allogeneic and autologous bone marrow transplants, fluconazole 400 mg/day was effective when administered from the conditioning treatment period through the neutropenic period. In liver transplant recipients, either fluconazole 400 mg/day for 10 weeks or liposomal amphotericin B 1 mg/kg/day for 5 days significantly reduced the incidence of invasive fungal infections. However, one must be aware of the risk of fluconazole-resistant fungi and the possibility of selection. In patients with a history of previous fungal infection, secondary prophylaxis may be of value, although data are limited. For recipients of transplants other than bone marrow or liver, there are insufficient data to recommend general prophylaxis.     

Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by Broth microdilution,disk diffusion,and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001

The ARTEMIS Global Antifungal Susceptibility Program (ARTEMIS Program) was initiated in 2001 to provide focused surveillance of the activities of fluconazole and voriconazole against Candida spp. isolated from blood and other normally sterile sites. A total of 1,586 episodes of infection were detected at 61 international study sites. Overall, 57.7% of the infections were due to Candida albicans, followed by C. glabrata (14.8%), C. parapsilosis (12.5%), C. tropicalis (9.4%), C. krusei (2.7%), and C. lusitaniae (1.5%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (for 99% of the isolates the MICs were 相似文献