Fluconazole Susceptibility Research Articles

The activity of echinocandins, amphotericin B and voriconazole against fluconazole-susceptible and fluconazole-resistant Brazilian Candida glabrata isolates

The extensive use of azole antifungal agents has promoted the resistance of Candida spp to these drugs. Candida glabrata is a problematic yeast because it presents a high degree of primary or secondary resistance to fluconazole. In Brazil, C. glabrata has been less studied than other species. In this paper, we compared the activity of three major classes of antifungal agents (azoles, echinocandins and polyenes) against fluconazole-susceptible (FS) and fluconazole-resistant (FR) C. glabrata strains. Cross-resistance between fluconazole and voriconazole was remarkable. Among the antifungal agents, the echinocandins were the most effective against FS and FR C. glabrata and micafungin showed the lowest minimal inhibitory concentrations.

Neonatal invasive candidiasis in Tunisian hospital: incidence, risk factors, distribution of species and antifungal susceptibility

The aim of our study was to assess epidemiological features of neonatal invasive candidiasis in Farhat Hached hospital of Sousse, Tunisia, including incidence, risk factors, mortality, species distribution and antifungal susceptibility. Laboratory data from 1995 to 2010 and medical records of 127 invasive candidiasis cases were reviewed. We tested the susceptibility of 100 Candida sp isolates by using ATB fungus(®) 3 and to fluconazole by using E-test(®) strips. A total of 252 cases of neonatal invasive candidiasis occurred over the study period. The incidence increased 1.8-fold from 1995 to 2006 and decreased fourfold from 2007 to 2010. Candida albicans was the predominant species up to 2006 and a shift in the species spectrum was observed with increase of the non-albicans species mainly C. parapsilosis. The agreement between the ATB Fungus(®) and the E-test(®) for determining fluconazole susceptibility was high. All tested isolates were susceptible to fluconazole, flucytosine, amphotéricine B and voriconazole and the itraconazole resistance rate was 5%. The mortality rate was 63%. The invasive candidiasis incidence increased from 1995 to 2006 and decreased from 2007 to 2010. The spectrum of Candida species and the lack of fluconazole-resistant strains argue for the usefulness of fluconazole as an empiric treatment.

Extensive Genetic Diversity within the Dutch Clinical Cryptococcus neoformans Population

A set of 300 Dutch Cryptococcus neoformans isolates, obtained from 237 patients during 1977 to 2007, was investigated by determining the mating type, serotype, and AFLP and microsatellite genotype and susceptibility to seven antifungal compounds. Almost half of the studied cases were from HIV-infected patients, followed by a patient group of individuals with other underlying diseases and immunocompetent individuals. The majority of the isolates were mating type α and serotype A, followed by αD isolates and other minor categories. The most frequently observed genotype was AFLP1, distantly followed by AFLP2 and AFLP3. Microsatellite typing revealed a high genetic diversity among serotype A isolates but a lower diversity within the serotype D set of isolates. One patient was infected by multiple AFLP genotypes. Fluconazole and flucytosine had the highest geometric mean MICs of 2.9 and 3.5 μg/ml, respectively, while amphotericin B (0.24 μg/ml), itraconazole (0.08 μg/ml), voriconazole (0.07 μg/ml), posaconazole (0.06 μg/ml), and isavuconazole (0.03 μg/ml) had much lower geometric mean MICs. One isolate had a high flucytosine MIC (>64 μg/ml), while decreased susceptibility (≥16 μg/ml) for flucytosine and fluconazole was found in 9 and 10 C. neoformans isolates, respectively.

Impact of Prior Inappropriate Fluconazole Dosing on Isolation of Fluconazole-Nonsusceptible Candida Species in Hospitalized Patients with Candidemia

Prior use of fluconazole is a modifiable risk factor for the isolation of fluconazole-nonsusceptible Candida species. Optimization of the use of fluconazole by appropriate dose or duration may be able to minimize the risk of resistance. The objective of this study was to evaluate the effects of prior fluconazole therapy, including the dose and duration, on fluconazole susceptibility among Candida species isolated from hospitalized patients with candidemia. A retrospective cohort study of hospitalized patients with a first occurrence of nosocomial candidemia, from 2006 to 2009, was carried out. The relationships between the initial dose and duration of prior fluconazole therapy and the isolation of fluconazole-nonsusceptible Candida species were assessed. An initial fluconazole dose greater than 2 mg/kg and less than 6 mg/kg of body weight was considered suboptimal. A total of 177 patients were identified, of whom 133 patients aged 61 ± 16 years (56% male, 51% Caucasian, 51% with an APACHE II score of ≥ 15) had candidemia more than 2 days after the hospital admission day. Nine of 107 (8%) patients with fluconazole-susceptible Candida species and 9 of 26 (35%) patients with fluconazole-nonsusceptible Candida species had prior fluconazole exposure (risk ratio [RR], 3.03; 95% confidence interval [95% CI], 1.57 to 5.86; P, 0.0022). Preexposure with an initial dose of fluconazole greater than 2 mg/kg and less than 6 mg/kg occurred in 3 of 9 (33%) and 8 of 9 (89%) patients with fluconazole-susceptible and fluconazole-nonsusceptible Candida species, respectively (P, 0.0498). We conclude that patients with candidemia due to fluconazole-nonsusceptible Candida species were more likely to have received prior fluconazole therapy. Suboptimal initial dosing of prior fluconazole therapy was associated with candidemia with fluconazole-nonsusceptible Candida species.

An alternative respiratory pathway on Candida krusei: implications on susceptibility profile and oxidative stress

Our aim was to detect the presence of an alternative oxidase (AOX) in Candida krusei clinical strains and its influence on fluconazole susceptibility and in reactive oxygen species (ROS) production. Candida krusei clinical isolates were tested to evaluate the presence of AOX. Debaromyces hansenii 2968 (AOX positive) and Saccharomyces cerevisiae BY4742 (AOX negative) were used as control strains. Measurements of oxygen consumption were performed in the presence of 1mM KCN, an inhibitor of the classical respiratory chain, and 5mM salicylhydroxamic acid (SHAM). AOX expression was monitored by Western blotting using an AOX monoclonal antibody. Interactions between fluconazole and SHAM were performed using checkerboard assay. ROS production was evaluated in the presence of SHAM plus fluconazole, H(2) O(2) , menadione, or plumbagin. AOX was present in all C.krusei tested. The combination of fluconazole with SHAM resulted in an indifferent effect. In the presence of SHAM, the treatment with ROS inductors or fluconazole increased ROS production, except in the AOX-negative strain. An alternative respiratory pathway resistant to cyanide is described for the first time as a characteristic of C.krusei species. This AOX is unrelated to fluconazole resistance; however, it protects C.krusei from oxidative stress.

Susceptibility to antifungal agents and genotypes of Brazilian clinical and environmental Cryptococcus gattii strains

There are few reports concerning the in vitro antifungal susceptibility of clinical and environmental Cryptococcus gattii isolates. In this study, we performed polymerase chain reaction–restriction fragment length polymorphism to investigate the molecular subtypes of 50 clinical and 4 environmental Brazilian isolates of C. gattii and assessed their antifungal susceptibility for fluconazole (FLU) and amphotericin B (Amb) according to recent recommendations proposed for antifungal susceptibility testing of nonfermentative yeasts. Time–kill curve studies were performed using RPMI 1640 medium to analyze the fungicidal effect of AmB. We found 47 VGII (94%) molecular types and 3 VGI (6%) types among the clinical isolates. The environmental isolates were VGII (75%) subtype and VGI (25%) subtype. The FLU-MIC ranged from 1 to 64 mg L−1, and MIC50/MIC90 values were, respectively, 8/16 mg L−1. For AmB, the MICs were low and homogeneous, ranging from 0.12 to 0.5 mg L−1, for VGI or VGII. The time required to reach the fungicidal end point (99.9% killing) was 6 h for the majority of strains (64%), but viable cells of VGII were still present after 48 h of exposition. We pointed out the occurrence of high FLU-MICs for C. gattii isolates with highest values for VGII. Our data also suggest that the rate of killing of C. gattii by AmB is strain dependent, and viable cells of VGII genotype strains were still observed after an extended incubation time, addressing future studies to determine whether the in vitro fungicidal activity could be clinically relevant.

Cellular characterisation of Candida tropicalis presenting fluconazole-related trailing growth

We assessed fluconazole susceptibility in 52 Candida tropicalis clinical strains using seven antifungal susceptibility methods, including broth microdilution (BMD) [standard M27 A3 (with neutral and acid pH), ATB Fungus 3, Vitek 2 system and flow cytometric analysis] and agar-based methods (disk diffusion and E-test). Trailing growth, detection of cell-associated secreted aspartic proteases (Saps) and morphological and ultrastructural traits of these clinical strains were also examined. The ranges of fluconazole 24 h-minimum inhibitory concentration (MIC) values were similar among all methods. The essential agreement among the methods used for MIC determinations was excellent and all methods categorised all strains as susceptible, except for one strain that showed a minor error. The presence of the trailing effect was assessed by six methods. Trailing positivity was observed for 86.5-100% of the strains. The exception was the BMD-Ac method where trailing growth was not observed. Morphological and ultrastructural alterations were detected in C. tropicalis trailing cells, including mitochondrial swelling and cell walls with irregular shapes. We tested the production of Saps in 13 C. tropicalis strains expressing trailing growth through flow cytometry. Our results showed that all of the C. tropicalis strains up-regulated surface Sap expression after 24 h or 48 h of exposure to fluconazole, which was not observed in untreated yeast strains. We concluded that C. tropicalis strains expressing trailing growth presented some particular features on both biological and ultrastructural levels.

Azole Resistance by Loss of Function of the Sterol Δ 5,6 -Desaturase Gene ( ERG3 ) in Candida albicans Does Not Necessarily Decrease Virulence

The inactivation of ERG3, a gene encoding sterol Δ⁵,⁶-desaturase (essential for ergosterol biosynthesis), is a known mechanism of in vitro resistance to azole antifungal drugs in the human pathogen Candida albicans. ERG3 inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified a C. albicans clinical isolate (VSY2) with high-level resistance to azole drugs in vitro and an absence of ergosterol but normal filamentation. Sequencing of ERG3 in VSY2 revealed a double base deletion leading to a premature stop codon and thus a nonfunctional enzyme. The reversion of the double base deletion in the mutant allele (erg3-1) restored ergosterol biosynthesis and full fluconazole susceptibility in VSY2, confirming that ERG3 inactivation was the mechanism of azole resistance. Additionally, the replacement of both ERG3 alleles by erg3-1 in the wild-type strain SC5314 led to the absence of ergosterol and to fluconazole resistance without affecting filamentation. In a mouse model of disseminated candidiasis, the clinical ERG3 mutant VSY2 produced kidney fungal burdens and mouse survival comparable to those obtained with the wild-type control. Interestingly, while VSY2 was resistant to fluconazole both in vitro and in vivo, the ERG3-derived mutant of SC5314 was resistant only in vitro and was less virulent than the wild type. This suggests that VSY2 compensated for the in vivo fitness defect of ERG3 inactivation by a still unknown mechanism(s). Taken together, our results provide evidence that contrary to previous reports inactivation of ERG3 does not necessarily affect filamentation and virulence.

Genotyping and fluconazole susceptibility of Candida albicans strains from patients with vulvovaginal candidiasis in Jos, Nigeria

Objective To investigate the fluconazole susceptibility of the genotypes of Candida albicans ( C. albicans) strains isolated from patients with vulvovaginal candidiasis (VVC) in Jos, Plateau State, Nigeria. Methods A total of one hundred and seventy seven (177) Candida isolates were examined. The strains were obtained from 320 female patients with VVC and were identified using both phenotypic and molecular methods. Their genotypes were determined, based on the presence or absence of a transposable intron in the 25S rDNA. Results Eighty four (84) strains were recognized as being C. albicans and all the 84 C. albicans strains resulted to be genotype A. Antifungal susceptibility testing showed that 13 of those isolates (15.48%) were resistant to fluconazole. Conclusions Based on these data, we concluded that C. albicans genotype A was common among VVC patients in Jos, and resistance to fluconazole is quite high. To our knowledge, this is the first study that reports C. albicans genotypes in Jos and its resistance to fluconazole.

Effect of pH on In Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

The treatment of vulvovaginal candidiasis (VVC) due to Candida glabrata is challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite of in vitro susceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on the in vitro activity of 11 antifungal agents against 40 C. glabrata isolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibility C. albicans strains. In vitro susceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH, C. glabrata isolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC(90) for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7, C. albicans strains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitive C. albicans isolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrent C. glabrata vaginitis, clinicians should recognize the limitations of in vitro susceptibility testing utilizing pH 7.0.

The Changing Epidemiology of Oropharyngeal Candidiasis in Patients with HIV/AIDS in the Era of Antiretroviral Therapy.

The impact of antiretroviral therapy (ART) on opportunistic conditions in HIV patients continues to evolve. We specifically studied the changing epidemiology of oropharyngeal candidiasis (OPC) in 215 HIV/AIDS patients. Status of yeast colonization was assessed from oral rinse samples, and preliminary yeast identification was made using CHROMagar Candida and confirmed with standard microbiological techniques and/or molecular sequencing. Susceptibility to fluconazole was determined by CHROMagar Candida agar dilution screening and CLSI broth microdilution. 176 (82%) patients were colonized and 59 (27%) patients had symptomatic OPC. Candida albicans was the most prevalent species, though C. glabrata and C. dubliniensis were detected in 29% of isolates. Decreased fluconazole susceptibility occurred in 10% of isolates. Previous ART reduced the risk of OPC, while smoking increased the risk of colonization. Oral yeast colonization and symptomatic infection remain common even with advances in HIV therapy. C. albicans is the most common species, but other yeasts are prevalent and may have decreased susceptibility to fluconazole.

Amphotericin B and fluconazole susceptibility of Candida species determined by cell‐chip technology

The aim of this study was to apply the microfluidic cell-chip technology for susceptibility testing. The cell-chip technology was tested with ATCC Candida strains to determine their viability and susceptibility against amphotericin B and fluconazole. Fungal cells were labelled by Sytox Green, and measurements were carried out in the cell chips of the Agilent Bioanalyzer 2100 system. Results obtained by the chip technology were compared with the standard macrodilution method and conventional flow cytometry. Determination of minimum inhibitory concentration values was based on the differentiation between living and dead cells. The cell-chip method was found to be suitable for the detection of Candida cells, for the differentiation between dead and living cells and for the determination of amphotericin B and fluconazole susceptibility of fungal cells. The minimum inhibitory concentration values obtained by the standard macrodilution, the flow cytometry and the cell-chip method showed good correlation.

Fungicidal activity of the human peptide hepcidin 20 alone or in combination with other antifungals against Candida glabrata isolates

Candida glabrata infections are often difficult to eradicate due to the intrinsically low susceptibility to azoles of this species. In addition, C. glabrata has also been shown to be insensitive to several cationic peptides, which have been shown to be promising novel therapeutic candidates for the treatment of fungal infection. In this study, the in vitro fungicidal activity of the human cationic peptide hepcidin 20 (Hep-20) was evaluated against clinical isolates of C. glabrata with different levels of fluconazole susceptibility. Interestingly, all isolates were susceptible to Hep-20 (100–200 μg/ml) at pH 7.4, whereas the fungicidal effect of the peptide was higher (50 μg/ml) at acidic pH values. In addition, an increased antifungal activity was observed for Hep-20 with amphotericin B and a synergistic effect was demonstrated for the Hep-20/fluconazole and Hep-20/caspofungin combinations.

Species distribution and in vitro fluconazole susceptibility of clinical Candida isolates in a Brazilian tertiary-care hospital over a 3-year period

In this study, we aimed at identifying Candida isolates obtained from blood, urine, tracheal secretion, and nail/skin lesions from cases attended at the Hospital Universitário de Londrina over a 3-year period and at evaluating fluconazole susceptibilities of the isolates. Candida isolates were identified by polymerase chain reaction (PCR) using species-specific forward primers. The in vitro fluconazole susceptibility test was performed according to EUCAST-AFST reference procedure. Isolates were obtained from urine (53.4%), blood cultures (19.2%), tracheal secretion (17.8%), and nail/skin lesions (9.6%). When urine samples were considered, prevalence was similar in women (45.5%) and in men (54.5%) and was high in the age group >61 years than that in younger ones. For blood samples, prevalence was high in neonates (35%) and advanced ages (22.5%). For nail and skin samples, prevalence was higher in women (71.4%) than in men (28.6%). Candida albicans was the most frequently isolated in the hospital, but Candida species other than C. albicans accounted for 64% of isolates, including predominantly Candida tropicalis (33.2%) and Candida parapsilosis (19.2%). The trend for non-albicans Candida as the predominant species was noted from all clinical specimens, except from urine samples. All Candida isolates were considered susceptible in vitro to fluconazole with the exception of isolates belonging to the intrinsically less-susceptible species C. glabrata. Non-albicans Candida species were more frequently isolated in the hospital. Fluconazole resistance was a rare finding in our study.

The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in DNA damage sensitivity

BackgroundThe fungal pathogen Candida albicans is frequently seen in immune suppressed patients, and resistance to one of the most widely used antifungals, fluconazole (FLC), can evolve rapidly. In recent years it has become clear that plasticity of the Candida albicans genome contributes to drug resistance through loss of heterozygosity (LOH) at resistance genes and gross chromosomal rearrangements that amplify gene copy number of resistance associated genes. This study addresses the role of the homologous recombination factors Rad54 and Rdh54 in cell growth, DNA damage and FLC resistance in Candida albicans.ResultsThe data presented here support a role for homologous recombination in cell growth and DNA damage sensitivity, as Candida albicans rad54Δ/rad54Δ mutants were hypersensitive to MMS and menadione, and had an aberrant cell and nuclear morphology. The Candida albicans rad54Δ/rad54Δ mutant was defective in invasion of Spider agar, presumably due to the altered cellular morphology. In contrast, mutation of the related gene RDH54 did not contribute significantly to DNA damage resistance and cell growth, and deletion of either Candida albicans RAD54 or Candida albicans RDH54 did not alter FLC susceptibility.ConclusionsTogether, these results support a role for homologous recombination in genome stability under nondamaging conditions. The nuclear morphology defects in the rad54Δ/rad54Δ mutants show that Rad54 performs an essential role during mitotic growth and that in its absence, cells arrest in G2. The viability of the single mutant rad54Δ/rad54Δ and the inability to construct the double mutant rad54Δ/rad54Δ rdh54Δ/rdh54Δ suggests that Rdh54 can partially compensate for Rad54 during mitotic growth.

Influence of doxorubicin on fluconazole susceptibility and efflux pump gene expression ofCandida dubliniensis

The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.

Pharmacokinetic evaluation of fluconazole in critically ill patients

Introduction: Invasive candidiasis has emerged over the last few decades as an increasingly important nosocomial problem for the critically ill, affecting around 2% of intensive care unit patients. Although poor outcomes associated with invasive candidiasis among critically ill patients may relate to severe underlying disease processes and delayed institution of antifungal therapy, inadequate dosing of antifungal agents may also contribute.Areas covered: This drug evaluation provides a critical appraisal of the published literature pertaining to the pharmacokinetics of fluconazole in critically ill, obese or severely burned patients, including those receiving acute renal replacement therapy. The pharmacodynamics of fluconazole is also covered, as well as the likely clinical implications for optimal dosing and the toxicity of fluconazole. Last, variations in fluconazole susceptibility patterns of Candida spp. are also discussed.Expert opinion: Recently, there has been an increased but geographically variable prevalence of non-albicans Candida spp., causing invasive candidiasis and an overall trend towards reduced fluconazole susceptibility. The pathophysiological changes of critical illness, coupled with a lack of dose finding studies, support the use of local susceptibility patterns to guide fluconazole dosing until such time as pharmacokinetic–pharmacodynamic information to guide optimal fluconazole dosing strategies and pharmacodynamic targets becomes available.

Bloodstream and non-invasive isolates ofCandida glabratahave similar population structures and fluconazole susceptibilities

We have compared multilocus sequence typing (MLST) and fluconazole susceptibility profiles of Candida glabrata bloodstream isolates obtained during active, population-based surveillance to those obtained from non-sterile sites of individuals with no evidence of fungal disease (i.e., non-invasive isolates) in the same US city during an overlapping time period. In each of the two populations, different proportions of the same six major sequence types (STs) encompassed 82% of the isolates. One ST was more prevalent in the candidemia population and two other STs were more prevalent in the non-invasive population, but the overall allelic frequencies within the groups suggested little, if any, genotypic diversity between them. Fluconazole susceptibility profiles of isolates from the patients in the two groups were not significantly different and were not associated with a particular sequence type. Our results support the hypothesis that C. glabrata strains causing bloodstream infections are genetically indistinguishable from those normally residing in/on the host, suggesting that relative pathogenicity may be closely tied to commensalism.

A scoring model of factors associated with Candida glabrata candidemia among critically ill patients

Candida species, including Candida glabrata (CG), are common causes of bloodstream infections among intensive care unit (ICU) patients. Many CG isolates have decreased susceptibility to fluconazole. Constructing a scoring model of factors associated with CG candidemia in ICU patients that can be used if fluconazole susceptibility testing is not readily available. We identified patients with candidemia that were admitted to the ICU of the Mayo Clinic in Rochester, Minnesota from 1998 to 2006. Using patient demographical and clinical data abstracted via chart review, a multivariable logistic regression model was developed to distinguish those with CG candidemia. We identified 246 patients with candidemia including 68 CG cases. Multivariable analysis identified four independent factors associated with CG candidemia: absence of renal failure, less than 7 days in the hospital, abdominal surgery and fluconazole use. The predictive ability of the model, based on the c-statistic, was 0.727. In a large ICU cohort, a scoring model that included four risk factors, which are readily ascertainable at the bedside, was created to distinguish candidemia due to CG from other causes of candidemia. The identification of risk factors associated with CG candidemia could aid physicians in the selection of the optimal initial antifungal therapy.

A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units

Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005–2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 72 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.