Previous Fluconazole Research Articles

Risk factors associated with fluconazole resistance in Candida parapsilosis candidemia: A case-case study.

Candida species are among the most important invasive pathogens in intensive care units (ICUs). Non-albicans species including Candida parapsilosis (C. parapsilosis) has increased in recent years. Fluconazole is the leading antifungal agent but resistance is a concern among C. parapsilosis species. The aim of this study was to determine the factors associated with fluconazole resistance in patients with candidemia due to C. parapsilosis in ICUs. This case-case study was conducted in a 750-bed, tertiary hospital between 2015 and 2021. Patients with fluconazole-resistant C. parapsilosis candidemia constituted the 'cases of interest' group and patients with fluconazole-susceptible C. parapsilosis candidemia constituted the 'comparison cases' group. Demographic and clinical data of the patients were recorded. Logistic regression analysis was performed using the backward elimination method to determine the independent predictors of fluconazole-resistant C. parapsilosis bloodstream infections. The study included 177 patients. In the cultures of these patients, 76 (43%) fluconazole-resistant, 13 (7.3%) fluconazole-reduced susceptible, and 88 (49.7%) fluconazole-susceptible isolates were found. In the regression analysis the risk factors for fluconazole-resistant C. parapsilosis bloodstream infection, malignancy, immunosuppressive treatment, history of intra-abdominal surgery, hypoalbunemia, previous fluconazole use, and SOFA score were found to be associated in univariate analysis. In multivariate regression analysis, history of intra-abdominal surgery (OR: 2.16; 95% CI: 1.05-4.44), hypoalbuminemia (OR: 2.56; 95% CI: 1.06-6.17) and previous fluconazole use (OR: 3.35; 95% CI: 1.02-11) were found to be independent predictors. In this study, a significant correlation was found between candidemia due to fluconazole-resistant C. parapsilosis in ICUs and intra-abdominal surgery, hypoalbuminemia, and previous fluconazole use. C. parapsilosis isolates and fluconazole resistance should be continuously monitored, strict infection control measures should be taken and antifungal stewardship programs should be implemented.

A 14-Year Cohort of Candidemia in the Pediatric Population in a Tertiary Center in Jerusalem: Clinical Characteristics, Antifungal Susceptibility, and Risk Factors for Mortality.

Candida spp. can cause bloodstream infection and is associated with significant mortality. The proportion of fluconazole-resistant Candida non-albicans has increased over the years, and empirical fluconazole maybe inappropriate. In this retrospective study, we analyzed clinical characteristics, antifungal resistance patterns, and mortality in children with candidemia treated at a tertiary medical center in Jerusalem between 2009 and 2022. A total of 122 children developed 127 candidemia episodes with 132 Candida isolates. Half the episodes occurred in immunocompromised children. Septic shock was present in 27 (21.3%). Candida non-albicans was responsible for 71/132 (56.5%) episodes; 16/132 (12.1%) of isolates were fluconazole-resistant. The rate of Candida non-albicans was significantly higher in fluconazole-resistant episodes (90 vs. 50.5%, p = 0.02). Prolonged severe neutropenia and previous fluconazole exposure were more frequent in fluconazole-resistant episodes. Thirty-day mortality was 25 (19.7%). Greater mortality, as shown by multivariate analysis, was associated with candidemia contracted in the pediatric intensive care unit (PICU), previous use of azoles or carbapenems, and in the presence of shock. In conclusion, mortality rates in our study were higher than those previously reported. In suspected infection associated with factors which we found to increase the probability of mortality-PICU admission, shock, and earlier azole or carbapenems exposure-empirical antifungals should be considered.

The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis, 21.6%; C. tropicalis, 21.6%; C. glabrata, 1.4%) were included and analysed in this study. Risk factors, clinical and microbiological characteristics and outcomes of patients with C. auris and non-auris Candida species (NACS) candidemia were compared. Previous fluconazole exposure was significantly higher in C. auris candidemia patients (OR 3.3; 1.15-9.5). Most C. auris isolates were resistant to fluconazole (86.3%) and amphotericin B (59%) whilst NACS isolates were generally susceptible. No isolates resistant to echinocandins were detected. The average time to start antifungal therapy was 3.6 days. Sixty-three (85.1%) patients received adequate antifungal therapy, without significant differences between the two groups. The crude mortality at 30 and 90 days of candidemia was up to 37.8% and 40.5%, respectively. However, there was no difference in mortality both at 30 and 90 days between the group with candidemia by C. auris (31.8%) and by NACS (42.3%) (OR 0.6; 95% IC 0.24-1.97) and 36.4% and 42.3% (0.77; 0.27-2.1), respectively. In this study, mortality due to candidemia between C. auris and NACS was similar. Appropriate antifungal therapy in both groups may have contributed to finding no differences in outcomes.

Implications of Evolving and Emerging Pharmacokinetic-Pharmacodynamic Research for Triazoles and Echinocandins

Clinicians should be encouraged to use pharmacokinetic-pharmacodynamic (PK-PD) studies to optimize antifungal drug dosing in the absence of robust comparative effectiveness data or in cases where evidence of causality has not yet been firmly established. The purpose of this article is to review how new triazole and echinocandin PK-PD studies have contributed to our current understanding of antifungal selection and dose optimization against invasive fungal infections. Emerging infections such as C. auris and novel antifungal drugs such as rezafungin will also be highlighted. Future research endeavors are suggested where currently robust clinical outcomes data associated with PK-PD target attainment are lacking. Recent results from clinical fluconazole PK-PD studies may indicate that unique AUC24/MIC thresholds exist for specific Candida species. The inability of recent studies to confirm previous fluconazole AUC24/MIC clinical PK-PD targets of 11 to 400 may also be due to previously unrecognized PK variability in special patient populations such as those with augmented renal clearance. A free AUC24/MIC threshold of 25 appears to be conserved across the azole antifungal class in animal models of invasive candidiasis. Current therapeutic drug monitoring guidance with voriconazole, posaconazole, and itraconazole has been used to indirectly confirm pre-clinical AUC24/MIC PK-PD targets in invasive candidiasis and aspergillosis. Elucidation of the PK-PD targets in pre-clinical models has led to successful isavuconazole dose optimization in human studies and has contributed to dosing recommendations for the novel echinocandin rezafungin. PK-PD research will also be important in guiding antifungal selection against infections caused by emerging pathogens, such as Candida auris, and those caused by fungi for which reduced susceptibility is a growing concern, including Coccidioides species and azole-resistant Aspergillus fumigatus. PK-PD research may be used to inform treatment decisions for rare fungal infections, infections with rapidly changing epidemiology, in patient populations expected to have altered pharmacokinetics, for novel antifungal drugs or those with new formulations, and in cases where evidence of causality cannot be established from large randomized comparative studies. A number of animal models have been developed and more clinical PK-PD studies are being conducted. In the absence of clinical PK-PD outcome data in human studies, researchers have expanded the use of currently available therapeutic drug monitoring to gain insight into possible PK-PD targets.

Breakthrough candidaemia in the era of broad-spectrum antifungal therapies

We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45–21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.

Single-center retrospective study of the incidence of, and risk factors for, non-C. albicansinvasive candidiasis in hospitalized patients in China

The aims of this study were to establish the incidence of invasive candidiasis (IC) in a Beijing hospital, to identify risk factors associated with IC caused by non-C. albicans Candida (NAC), and to determine risk factors for infection caused by NAC species not susceptible to fluconazole. Clinical data from 141 patients admitted to Beijing Chaoyang Hospital (from 2001-2010) diagnosed with IC were retrospectively analyzed. The incidence of IC increased during the 10-year period, but the proportion due to NAC did not change significantly in that of 141 cases, 55 (39%) were due to NAC and 86 (61%) to C. albicans (CA). The NAC species isolated included C. tropicalis (25 of 141, 18%), C. glabrata (14 of 141, 9.9%), C. parapsilosis (eight of 141, 5.7%), C. krusei (three of 141, 2.1%) and C. lusitaniae (one of 141, 0.71%); other Candida species accounted for four of the 141 cases (2.8%). Twenty-one isolates (38%) of NAC were not susceptible to fluconazole. Total parenteral nutrition (TPN) (OR 4.2; 95% CI 3.5-58; P < 0.001) and previous fluconazole therapy (OR 7.7; 95% CI 2.2-27; P = 0.001) were risk factors for invasive NAC candidiasis, whereas patient age ≥65 years (OR 0.37; CI 0.16-0.88; P = 0.025) and invasive mechanical ventilation (OR 0.22; CI 0.069-0.70; P =0.010) were connected with invasive CA candidiasis. Prior fluconazole therapy was a risk factor (P = 0.007) for infections caused by NAC not susceptible to fluconazole. In conclusion, TPN and prior fluconazole therapy are independent risk factors for NAC infection, while prior fluconazole therapy is a risk factor for infection due to NAC not susceptible to fluconazole.

Fluconazole exposure rather than clonal spreading is correlated with the emergence of Candida glabrata with cross-resistance to triazole antifungal agents

The emergence of antifungal resistance in Candida species has raised concern in recent years, especially resistance toward triazole. Several newer triazole antifungal agents have been introduced which have a broader spectrum for fungal infections, such as voriconazole. However, cross-resistance among triazoles is a major concern with regard to their clinical application. Antifungal susceptibility was performed using E-test for 166 clinical isolates (29 blood and 137 nonblood isolates) in 2003 and 2004. We applied pulsed-field gel electrophoresis for genotyping. Ninety isolates of C. albicans, 47 isolates of C. tropicalis, 27 isolates of C. glabrata, and two isolates of C. krusei were included. All isolates were susceptible to amphotericin B. Eleven (40.7%) of the 27 C. glabrata had intermediate resistance to caspofungin. Forty-seven (28.3%) of the 166 isolates were not susceptible to fluconazole, including two C. albicans, 16 C. tropicalis, 27 C. glabrata, and two C. krusei isolates. All except seven of the C. glabrata isolates were susceptible to voriconazole. All the triazole drugs had a positive correlation among their minimum inhibitory concentrations (MICs). Fluconazole MIC was a good predictor for susceptibility to voriconazole, as determined using a receiver operating characteristic curve. Furthermore, a high diversity of pulsotypes for the 27 clinical isolates of C. glabrata was observed. Previous fluconazole exposure within 3 months was associated with reduced triazole susceptibility for C. glabrata. We demonstrated a significant positive correlation of MIC values among the four tested triazole drugs. No amphotericin B and caspofungin resistant isolates were found in this study. The cross-resistance to triazole among C. glabrata isolates was associated with previous fluconazole exposure as opposed to clonal spreading. Selection pressure due to fluconazole use may play a major role in triazole cross-resistance.

Predictors of candidaemia caused by non-albicans Candida species: results of a population-based surveillance in Barcelona, Spain

Although Candida albicans (CA) is the most common cause of Candida bloodstream Infections (BSIs), recent studies have observed an Increasing percentage of candidaemias caused by non-albicans Candida species (NAC). In the present study, we attempted to identify the predictors of candidaemia due to NAC compared to CA. We analyzed data from an active population-based surveillance in Barcelona (Spain) from January 2002 to December 2003. Factors associated with NAC fungaemia were determined by multivariate analysis. A total of 339 episodes of Candida BSI, in 336 patients (median age 63 years, interquartile range: 41–72 years), were included. CA was the most commonly isolated (52%), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8.6%), Candida krusei (3.4%) and other NAC spp. (3%). Overall, 48% of cases were due to NAC spp. Multivariate logistic regression analysis identified factors associated with a risk of BSI due to NAC spp.: having received a haematologic transplant (OR 10.8; 95% CI 1.31–90.01; p 0.027), previous fluconazole exposure (OR 4.47; 95% CI 2.12–9.43; p <0.001) and neonatal age (OR 4.42; 95% CI 1.63–12.04; p 0.004). Conversely, previous CA colonization (OR 0.33; 95% CI 0.19–0.57; p 0.001) and previous antibiotic use (OR 0.42; 95% CI 0.21–0.85; p 0.017) were associated with CA fungaemia compared to NAC. In conclusion, NAC candidaemia comprised 48% of cases in our series. Predictors of NAC include having received a haematologic transplant, neonatal age and previous fluconazole use.

Risk Factors for Fluconazole-Resistant Candidemia

Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR]=4.94; 95% confidence interval [CI]=1.50 to 16.20; P=0.008), chronic renal disease (OR=4.82; 95% CI=1.47 to 15.88; P=0.01), and previous fluconazole exposure (OR=5.09; 95% CI=1.66 to 15.6; P=0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.

Risk factors for fluconazole resistance in patients with Candida glabrata bloodstream infection: Potential impact of control group selection on characterizing the association between previous fluconazole use and fluconazole resistance

Although Candida glabrata is an emerging infection, risk factors for fluconazole resistance in patients with C glabrata bloodstram infection (BSI) have not been well elucidated. A case-control study was conducted to evaluate the primary risk factor of interest, previous fluconazole use, adjusting for demographics, comorbidities, time at risk, and antimicrobial exposure and assessing for effect modification. Secondary analyses were performed limiting the case group to C glabrata BSIs with a minimum inhibitory concentration (MIC) > or =64 microg/mL. Previous fluconazole use was not a significant risk factor for fluconazole-resistant C glabrata BSI in primary analysis (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 0.7-3.2) but was borderline significant in secondary analysis (aOR, 3.2; 95% CI, 0.9-11.3). Increased time at risk was an independent risk factor in primary (aOR, 1.02; 95% CI, 1.002-1.04) and secondary analyses (aOR, 1.03; 95% CI, 1.004-1.06). Increased time at risk was the only significant risk factor for fluconazole resistance. Future studies are needed to further evaluate the relationship between previous fluconazole use and fluconazole-resistant C glabrata BSI isolates with MIC > or =64 microg/mL.

Risk Factors for Fluconazole-Resistant Candida glabrata Bloodstream Infections

Bloodstream infections (BSIs) caused by Candida glabrata have increased substantially. Candida glabrata is often associated with resistance to fluconazole therapy. However, to our knowledge, risk factors for fluconazole-resistant C glabrata BSIs have not been studied. A case-case-control study was conducted at 3 hospitals from January 1, 2003, to May 31, 2007. The 2 case groups included patients with fluconazole-resistant C glabrata BSIs (minimum inhibitory concentration > or =16 microg/mL) and patients with fluconazole-susceptible C glabrata BSIs (minimum inhibitory concentration < or =8 microg/mL). Hospitalized patients without C glabrata BSIs were randomly selected for inclusion in the control group and were frequency matched to cases on the basis of time at risk. Two case-control studies were performed using this shared control group. The primary risk factor of interest, previous fluconazole use, was evaluated at multivariate analyses, adjusting for demographic data, comorbid conditions, and antimicrobial exposures. We included 76 patients with fluconazole-resistant C glabrata BSIs, 68 patients with fluconazole-susceptible C glabrata BSIs, and 512 control patients. Previous fluconazole use (adjusted odds ratio [95% confidence interval], 2.3 [1.3-4.2]) and linezolid use (4.6 [2.2-9.3]) were independent risk factors for fluconazole-resistant C glabrata BSIs; previous cefepime use (2.2 [1.2-3.9]) and metronidazole use (2.0 [1.1-3.5]) were independent risk factors for fluconazole-susceptible C glabrata BSIs. Previous fluconazole use is a significant risk factor for health care-associated fluconazole-resistant C glabrata BSIs. Future studies will be needed to evaluate the effect of decreasing fluconazole use on rates of fluconazole-resistant C glabrata BSIs.

Empirical treatment of candidemia in intensive care units: Fluconazole or broad-spectrum antifungal agents?

The fear of candidemia caused by a fluconazole-resistant species of Candida is causing many intensive care units (ICUs) to switch empiric therapy from this drug to broad-spectrum antifungal agents. We studied the epidemiology and antifungal susceptibility of Candida isolates involved in cases of candidemia among adult and pediatric patients in ICUs from 1984 to 2006. We documented 307 episodes of candidemia in 307 patients, of which only eight episodes (2.6%) were caused by a fluconazole-resistant isolate. At least three of the eight patients from whom fluconazole-resistant strains were recovered had recently received fluconazole. Overall, only 1.6% of the episodes of candidemia caused by fluconazole-resistant strains (five patients) occurred in individuals with no evidence of previous fluconazole administration. In conclusion, the use of broad-spectrum antifungal agents is not justified in ICUs with a low proportion of candidemia episodes caused by fluconazole-resistant strains of Candida.

Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia

To describe the evolving epidemiology of fungal bloodstream infections in critically ill and noncritically ill patients and to identify predictors of infection with non-albicans yeast species. Retrospective case series. Two academic, tertiary care centers. All persons during a 4-yr period who developed fungemia. None. We initially compared subjects with Candida albicans vs. alternative yeast. In a sensitivity analysis, we compared persons with potentially fluconazole-resistant organisms (Candida glabrata and Candida krusei) to those with other fungi. We also repeated these analyses in the subgroup of persons in the intensive care unit when they developed fungemia. The study cohort included 245 patients (60% in the intensive care unit), and C. albicans accounted for 52% of infections, whereas C. glabrata represented 20% of cases. The distribution of isolates was similar in both intensive care unit patients and those on the wards. In the entire population, no variable, including both previous fluconazole exposure and severity of illness, correlated with the fungemia due to a non-albicans species. In our sensitivity analysis, no factor was independently associated with a potentially fluconazole-resistant yeast. For the subgroup of subjects whose fungemia was diagnosed while they were in the intensive care unit, no variable differentiated C. albicans from non-albicans isolates. Non-albicans yeast are common both in the intensive care unit and on the wards. Simple clinical factors do not allow the clinician to effectively identify patients likely infected with non-albicans pathogens or with possible fluconazole-resistant fungi.

Surveillance of triazole susceptibility of colonizing yeasts in patients with haematological malignancies

The species distribution and antifungal susceptibility of yeasts isolated from colonization cultures, and the contribution of previous fluconazole prophylaxis to the emergence of resistance, was prospectively studied in 87 neutropenic patients treated for haematological malignancies. Minimal inhibition concentrations (MICs) to fluconazole, itraconazole and voriconazole for 123 yeast isolates (65 Candida albicans, 22 Candida glabrata, 15 Saccharomyces cerevisiae, 5 Candida krusei, 5 Candida norvegensis, 11 other Candida spp.) were determined by E-test. Fluconazole MICs for Candida species and S. cerevisiae isolated from patients given prophylaxis were > or =2 mg/l in 24 of 40 (60%) isolates compared with 26 of 83 (31%) isolates from patients in the non-prophylaxis group (p =0.002). Among the non-albicans yeast species reduced susceptibility was common against itraconazole but was rarely found against voriconazole. Cross resistance between fluconazole and itraconazole was observed in 14 of all isolates, 4 of them also showing reduced susceptibility to voriconazole (MICs 4-8 mg/l). Fluconazole prophylaxis may contribute to emergence of less susceptible yeast strains also in patients with haematological malignancies not treated with allogeneic bone marrow transplantation.

FTIR characterization of Candida species: a study on some reference strains and pathogenic C. albicans isolates from HIV + patients

ATR–FTIR has been used together with principal components analysis to study some reference strains belonging to five different Candida species and 20 Candida albicans isolates from three HIV + patients under different fluconazole regimens. The five reference strains were easily differentiated by using first derivative spectra of the carbohydrate region comprising the spectral range 900–1200 cm −1. For the C. albicans clinical isolates, classification obtained by Fourier-transform infrared (FTIR) spectroscopy was compared with data from the genotypic method, PFGE. Results show a good correlation between the two methods for one patient who presented a partially conserved immune system with no previous fluconazole treatment, where all C. albicans strains isolated were susceptible to this antifungal agent. Divergences in the two methods appear for the two immuno-compromised patients receiving long-term fluconazole treatment. It is very probable that such iterative antifungal treatment can cause strong alterations in the yeast cell wall membrane and that the mismatch of the two techniques highlights the complex situation of strain-level identification and differentiation of clinical isolates originating from patients under prolonged treatment.

Who Gets Fluconazole-Refractory Mucosal Candidiasis?

Fluconazole-refractory mucosal candidiasis (FRMC) began to appear in HIV-positive patients nearly a decade ago. Previous fluconazole exposure has been

Patterns of fluconazole susceptibility in isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis due to Candida albicans.

We evaluated 119 episodes of oropharyngeal candidiasis due to C. albicans to study the patterns of fluconazole susceptibility of the isolates and the characteristics of the patients and to confirm the correlation between fluconazole susceptibility of isolates and therapeutic outcome. Sixty-one isolates were considered susceptible to fluconazole (MICs, < or = 0.5 microg/mL), 33 were intermediate (MICs, 1.0-8.0 microg/mL), and 25 were resistant (MICs, > or = 16.0 microg/mL). Patients infected with resistant strains had significantly lower CD4+ cell counts and a less recent AIDS diagnosis than patients infected with intermediate or susceptible strains. Previous fluconazole therapy and prophylaxis were significantly more frequent for patients infected with resistant and intermediate strains (P < .001). Decreased susceptibility to ketoconazole and itraconazole was observed in resistant and intermediate strains. Fluconazole treatment was ineffective for patients infected with resistant isolates; however, high doses of ketoconazole or itraconazole were successful for nine (81%) of them. Different patterns of fluconazole susceptibility among C. albicans strains are correlated with patients' characteristics and with therapeutic outcomes.

Detection and Significance of Fluconazole Resistance in Oropharyngeal Candidiasis in Human Immunodeficiency Virus-Infected Patients

The epidemiology and clinical significance of fluconazole resistance were assessed in a cohort of advanced human immunodeficiency virus (HIV)-infected patients with recurrent oropharyngeal candidiasis. Fifty patients were prospectively evaluated using a novel method of detecting fluconazole resistance with chromogenic media containing fluconazole; results were confirmed with macrobroth testing. Resistant yeasts, defined as MICs > or = 8 micrograms/mL, were detected in 16 (32%) of 50 patients: 7 (14%) had resistant Candida albicans, 7 (14%) had resistant non-C. albicans yeast, and 2 (4%) had mixed resistant yeasts. MICs were > or = 32 in 11 of 16 isolates. Previous fluconazole use and severe immunosuppression were risk factors for resistance. However, 5 of 26 patients had resistant isolates with no prior fluconazole use, and all were severely immunosuppressed. Despite the high prevalence of resistance, 48 patients clinically responded to fluconazole. Fluconazole-resistant C. albicans and non-C. albicans yeast infections are common in patients with advanced immunodeficiency, but clinical efficacy of fluconazole remains high.