Antifungal susceptibility pattern of Candida auris strains: Analysis of clinical strains in a tertiary-care educational university hospital.

Herein, we aimed to investigate the antifungal susceptibility pattern of Candida auris clinical strains in our setting Bahrain Oncology Center-King Hamad University Hospital-Bahrain. C. auris strains isolated from different clinical specimens in the Microbiology Laboratory from October-2021 to November-2022 were evaluated. Species-level identification of fungi was performed by MALDI-TOF (Bruker, Germany). Minimum inhibitory concentration (MIC) was determined either by E-test strips or by MICRONAUT MIC system based on CDC guidelines for C. auris antifungal interpretation. Fluconazole, amphotericin-B, voriconazole, and caspofungin susceptibility data of the clinical strains were analyzed. A total of 40 clinical isolates were included: 25% were blood culture isolates, 65% were urinary, and 10% were soft tissue isolates. Only 29 strains could be tested for amphotericin-B and 32 for voriconazole. Overall resistance pattern was as follows: 100% resistance to fluconazole, 2.5% resistance to caspofungin, and 0% resistance to amphotericin b. Median voriconazole MIC was 0.015 ug/ml (min 0.08, max= 0.064 ug/ml). We had no fluconazole-sensitive strain and only one caspofungin-resistant strain. A single isolate (2.5%), which was associated with candidemia, demonstrated resistance to two antifungal agents: fluconazole and caspofungin. No triple or quadruple drug resistant strain existed.

Ascending renal infection following experimental candiduria by Candida tropicalis in immunocompromised mice.

The present study evaluated renal infection resulting from the implantation of C. tropicalis in the bladder of immunosuppressed mice. Yeasts were implanted in two manners: planktonic and via preformed biofilm on a small catheter fragment (SCF). Renal histopathology and cultures was performed 72 and 144 h after cystotomy was carried out in mice from three groups: group I contained non-contaminated mice implanted with a sterile SCF; group II mice received a sterile SCF plus a yeast suspension containing 1 × 107 yeasts/mL in a planktonic form; group III mice were implanted with a SCF containing preformed C. tropicalis biofilm. Viable yeasts were found in the kidneys of mice from both groups II and III. However, after 72 h the planktonic cells (group II) invaded more quickly than the sessile cells (group III). Over a longer period (144 h), group III exhibited a more invasive infection (50% of the animals presented renal infection and the renal fungal load was 3.2 log10 CFU/g tissue) than in group II, where yeasts were not found. C. tropicalis introduced into the bladder in two ways (in planktonic or biofilm form) were able to reach the kidney and establish a renal fungal infection, causing interstitial disorders. The data of the present study therefore support the hypothesis of an ascending pathway for renal infections by C. tropicalis. Furthermore, the biofilm resulted in a greater and progressive risk of renal infection, attributed to the slow detachment of the yeasts.

Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates.

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.

In Vitro Activity of Nitroxoline in Antifungal-Resistant Candida Species Isolated from the Urinary Tract.

Infections by drug-resistant fungi are increasingly reported worldwide; however, only few novel antifungals are being developed. The old antimicrobial nitroxoline is currently repurposed for oral treatment of bacterial urinary tract infections (UTI). Previously, antifungal activity has been demonstrated and in contrast to many antifungals nitroxoline reaches high urinary concentrations. In this study, the activity of nitroxoline was assessed in vitro in a collection of yeasts from the German National Reference Centre for Invasive Fungal Infections. Susceptibility was determined by broth microdilution (BMD) and disk diffusion (DD). The collection comprised 45 Candida isolates originating from the urinary tract. MICs of amphotericin, anidulafungin and azoles were analyzed using EUCAST BMD. Among the collection isolates, resistance to antifungals was common, e.g., for fluconazole the MIC50/90 was 16/>64 mg/L; in contrast MIC50/90 of nitroxoline was 2/2 mg/L (MIC range 0.25-4 mg/L), which is at least two dilutions below the EUCAST breakpoint for uncomplicated UTI defined for E. coli (susceptible ≤ 16mg/L). Activity of nitroxoline was high irrespective of resistance to other agents. As BMD is labor-intensive, DD was investigated as an alternative method using three different agars. Nitroxoline disks produced large inhibition zones on all agars (≥19mm), but the correlation of MICs and zone diameters was low, with the highest correlation recorded for the CLSI recommended agar for antifungal DD (Pearson's r = -0,52). In conclusion, isolates of different Candida species are highly susceptible to nitroxoline, which could be a promising antimicrobial to treat candiduria caused by multidrug resistant yeasts.

Treatment of Candida urinary tract infections with micafungin in children.

BACKGROUND: Candida urinary tract infections (UTIs) are common nosocomial infections among critically ill patients hospitalized in pediatric intensive care Units (PICU). We aimed to report outcomes of critically ill pediatric patients who received micafungin for hospital acquired Candida UTIs. We analyzed treatment success rates and success rates among different Candida species. METHODS: This retrospective cohort study included patients who received micafungin for Candida UTI as first choice in our PICU between January 2017 and July 2018. Data, including demographic and clinical features, were retrospectively collected from medical files of the patients. Treatment efficacy was defined as resolution of clinical symptoms and a negative culture for Candida at day 14 after initiation of micafungin treatment. RESULTS: Twenty-four pediatric patients (median age 5.72 years, range, 2 months-16 years) were included in the present study. Fourteen (58.3%) patients had urinary catheters at the time of Candida isolation. Resolution of symptoms and a negative culture at day 3 of micafungin treatment were achieved in 17 (70.8%) and 14 (58.3%) patients, respectively. Moreover, 19 (79.2%) patients had a normal urine analysis and negative culture 14 days after initiation of micafungin treatment. Treatment responses did not statistically differ between Candida species. CONCLUSIONS: Micafungin is safe and efficacious in critically ill pediatric patients with Candida UTIs. Its efficacy in our pediatric population was as comparable to that observed in adult studies, therefore, it should be considered as an effective therapeutic option in Candida UTIs of critically ill pediatric patients.

Performance of Sysmex UF-5000 for candiduria screening.

In this study, we tested the performance of the Sysmex UF-5000 system to detect yeast-like cell (YLC) counting to screen for candiduria. Urine samples were screened for leukocyte and yeast amount by flow cytometry and results were compared with fungal culture results. A total of 56,749 urine samples were enrolled in this study. Urine culture and urinalysis of YLC data were used to evaluate the performance of YLC in diagnosing candiduria. Different cut-off values (YLC. 5, 10, 20, 50, 100/µl) were evaluated. Youden index was used to determine the ideal cut-off value, and the highest was 0.95 with 5 YLC/µl. When the cut-off value for YLC is 5 cells/µl, 95.15% of the samples were "negative" with flow cytometry and culture (NPV:100%). In conclusion, detection of YLC by flow cytometer (Sysmex UF-5000) can be a rapid alternative method to exclude candiduria prior to urine culture.

Management of candiduria in hospitalized patients: a single-center study on the implementation of IDSA guidelines and factors affecting clinical decisions.

Candiduria are common findings in clinic especially in hospitalized patients, while its significance remains undetermined. Since there are few criteria to follow, physicians tended to make decisions by personal experience in many cases in clinical practice. The present study was designed to unveil the present situation of candiduria management in hospitalized patients in clinical practice. A total of 251 hospitalized candiduria patients were retrospectively enrolled in the study. Clinical data on patient demographics, basic conditions, catheter using, urinary symptoms, laboratory data, and antifungal therapies were obtained from electronic medical records. The high rate of the candiduria cases were managed inappropriately after the introduction of the Infectious Diseases Association of America (IDSA) evidence-based recommendations, both in the management of urinary catheter and antifungal agents. Overtreatment was common in asymptomatic candiduria patients. For symptomatic patients, improper drug selections were not rare. In addition, a part of candiduria patients did not receive antifungal therapies although the IDSA recommends. A statistically significant difference was only found in hospital charges of symptomatic candiduria patients managed following IDSA or not. The recurrence rate, mortality, and hospital stay length were similar in candiduria patients regardless of the clinical management. Physicians tend to start empiric antifungal therapy for candiduria patients with pneumonia, multisite of Candida colonization, higher urine Candida CFUs, and long hospital stay. Candiduria has not received special attention today, and empirical antifungal treatment is common. IDSA guidelines are important to standardize the management of candiduria in clinic; however, the significance of the guidelines needs to be further clarified in future multicenter investigations.

Genotypic diversity and antifungal susceptibility pattern of Candida albicans species isolated from hospitalized paediatric patients with urinary tract infection in Iran.

AIMS: The present study aimed to determine the microsatellite length polymorphism (MLP) genotypic patterns and antifungal susceptibility profiles of Candida albicans isolated from patients with candiduria. METHODS AND RESULTS: DNA of 50 C. albicans isolates was used for molecular identification based on the ITS1 -5.8s-ITS2 region. MLP assays were performed to amplify three loci (EF3, CDC3 and HIS3), and PCR products were used for fragment analysis. Antifungal susceptibility tests were performed according to CLSI M27 4th ed guidelines. In all, 38 different genotypes were detected with the three polymorphic loci among C. albicans isolates, and only one genotype was homozygous. In comparison to other countries, our genotypes were divided into three clusters, two of which were linked to France and a third of which was linked to Austria. The genetic structures of the 50 C. albicans isolates revealed varied heterozygosity and significant Hardy-Weinberg equilibrium at the EF3 locus. Only one (2%) and four (8%) of isolates showed resistance to fluconazole and itraconazole, respectively. In C. albicans genotype G25, one (2%) of the isolates showed cross-resistance and non-wild-type resistance to posaconazole, itraconazole and fluconazole. CONCLUSION: MLP typing is a useful tool to analyse the genetic structure of C. albicans isolates. High genetic diversity (38 genotypes) was detected in the isolates tested here. Compared to isolates in other countries, the ones from our patients had a clear relationship with French and Austrian isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: Iranian isolates of C. albicans have a distinct genotype and show similarities only with French and Austrian isolates.

[Infectious emergencies in urology]. / Les urgences infectieuses en urologie.

OBJECTIVE: To report the nature, diagnosis and therapeutic strategy of infectious emergencies in urology. MATERIAL AND METHODS: Bibliographic research from Pubmed, Embase, and Google scholar in July 2021. A synthesis of the guidelines of national infectious diseases societies. RESULTS: Urosepsis and complicated urinary tract infection have a standardized definition. Diagnosis and therapeutic strategy are presented for upper tract urinary infection, male urinary infection, healthcare associated urinary infection, symptomatic canduria and urinary infections of the elderly. Appropriate antibiotherapy should be tailored to the degree of severity, bacterial ecosystem, patient characteristics et localization of the infection. CONCLUSION: Urinary infections can be critical and require immediate care. Knowledge of the guidelines and of appropriate diagnosis and therapeutics strategy improve care which should be rapidly applied, and collegial.

Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration.

Five Candida krusei isolates (susceptible and resistant) recovered from the urine of a kidney transplant patient treated with voriconazole (VRC) 200 mg twice daily for 20 days were studied. Eight unrelated clinical isolates of C. krusei were exposed in vitro to VRC 0.001 µg/ml for 30 days. Development of VRC transient resistance occurred in vivo, and induction of permanent resistance occurred in vitro Mostly, ABC1 and ERG11 genes were overexpressed, and a homozygous T418C mutation in the ERG11 gene was found.

Candida urinary tract infections in adults.

Candiduria is commonly seen in hospitalized patients and most of the patients are asymptomatic, but it may be due to cystitis, pyelonephritis, prostatitis, epididymo-orchitis or disseminated candidiasis. Major risk factors are diabetes mellitus, indwelling urinary catheters, use of broad-spectrum antibiotics, urinary obstruction, and admission to intensive care units. Candida urinary tract infections can be caused by hematogenous spread following candidemia, or retrograde route via the urethra. The presence of Candida species in urine in asymptomatic patients does not warrant antifungal therapy except neutropenic patients, very low-birth-weight infants and patients undergoing urologic procedures. Fluconazole is the treatment of choice for symptomatic infections, it achieves high urinary levels. The other azole antifungals and echinocandins do not reach sufficient urine levels. Amphotericin B deoxycholate is the alternative antifungal agent if fluconazole can not be used because of resistance, allergy or failure.

Clinical and microbiological features of candiduria in critically ill adult patients in Shiraz, Iran (2016-2018): deviations from international guidelines and fluconazole therapeutic failure.

Candiduria is common among patients admitted to intensive care units (ICUs); however, clinical and microbiological data are limited, which accounts for non-compliance with international guidelines, including over treatment of asymptomatic candiduria that promotes antifungal resistance. This prospective study included adult patients admitted to ICUs of five referral hospitals in Shiraz, Iran, during 2016-2018. Species were identified by MALDI-TOF MS, and antifungal susceptibility was assessed according to CLSI M27-A3/S4. Among 2086 patients, 162 and 293 developed candiduria and bacteriuria, respectively. In total, 174 yeast isolates were collected; 88.5% were Candida albicans (91/174; 52.2%), C. glabrata (38/174; 21.8%), and C. tropicalis (25/174; 14.3%). Antifungal resistance was rare; only two isolates (one C. tropicalis and one C. krusei) were fluconazole resistant. Symptomatic candiduria was noted in 31.4% of patients (51/162); only 37% (19/51) of them were treated and 36.82% (7/19) showed fluconazole therapeutic failure. Two symptomatic patients developed candidemia shortly after candiduria. Among asymptomatic patients, 31.5% (35/111) were overtreated with fluconazole. The mortality rate was 25.3% (41/162); it did not differ between symptomatic and asymptomatic patients. Our results indicate that deviation from standard-of-care treatment for candiduria is a matter of concern given the high rate of fluconazole therapeutic failure among patients with symptomatic candiduria. LAY SUMMARY: Candiduria is an underestimated clinical presentation among critically ill patients and detailed data are scarce in this regard. Given the high rate of fluconazole therapeutic failure and development of candidemia in some cases, the mistreatment of candiduria should not be overlooked by clinicians.

Performance of yeast-like cell counting (YLCC) using the Sysmex UF-1000i for clinical candiduria screening.

Candiduria is common in clinical practice. However, an effective and convenient assay to screen for candiduria is still needed. This study aimed to evaluate the performance of the Sysmex UF-1000i urine analyzer for yeast-like cell counting (YLCC) to screen for candiduria prior to urine culture. We retrospectively analyzed data from 5233 urine samples from 1813 patients, including 837 males and 976 females. Urine culture and urinalysis-obtained YLCC data were used to estimate the performance of YLCC in diagnosing candiduria. Different cutoff values were used to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The YLCC-positive rates differed according to the Candida colony-forming units (CFU) counts in the urine samples. A sharp drop in YLCC-positive rate (from 64.3 to 22.0%) was observed between the urine groups with 104 CFUs and 103 CFUs. A cutoff value of 0 YLCs/µL results in the highest Youden index (0.71) with 77.04% sensitivity and 93.68% specificity. In a group of 34 hospitalized candiduria patients with serial urinalysis data, 25 were YLCC-positive before urine culture. In conclusion, YLCC with the Sysmax UF-1000i could serve as an auxiliary technique to exclude culture-negative specimens prior to urine culture. Positive YLCC results could imply candiduria, especially when persistent YLCC-positive results were observed.

Successful eradication of chronic symptomatic Candida krusei urinary tract infection with increased dose micafungin in a liver and kidney transplant recipient: Case report and review of the literature.

Treatment of symptomatic candiduria is notoriously challenging because of the limited repository of antifungals that achieve adequate urinary concentrations. Fluconazole, amphotericin B-based products, and flucytosine are established treatment options for most Candida species. Candida krusei exhibits intrinsic resistance to fluconazole and decreased susceptibility to amphotericin B and flucytosine. In transplant patients, both amphotericin B-based products and flucytosine are less desirable because of their toxicities. Other triazole antifungals are unappealing because they do not achieve adequate urinary concentrations, have multiple toxicities, and interact with transplant-related immunosuppressive medications. Echinocandins are well-tolerated but have been traditionally deferred in the treatment of symptomatic funguria because of their poor urinary concentrations but there is a small but emerging body of literature supporting their use. Here, we present a case of successful eradication of chronic symptomatic C krusei urinary tract infection with micafungin 150 milligrams daily in a liver and kidney transplant recipient, and we review the literature on treatment of symptomatic candiduria.

Creation and assessment of a clinical predictive model for candidaemia in patients with candiduria.

Candidaemia is the most common clinical presentation of invasive candidiasis and is a major cause of morbidity and mortality. Candiduria is a predictor for candidaemia; however, patient characteristics that are associated with concurrent candidaemia in the setting of candiduria are unclear. Identifying these characteristics could aid in the early detection of systemic disease. We performed a retrospective cohort analysis of hospitalised patients with candiduria at our institution over a 13-year period. Our evaluation of patient characteristics included demographics, comorbidities, medications, procedures, devices, vital signs and laboratory values. We developed a multivariable logistic model to identify factors associated with candidaemia in patients with candiduria. We identified 4240 patients with candiduria, 263 (6.2%) of whom had candidaemia. Predictors for increased risk of candidaemia with candiduria included hospitalisations > 12 days, central venous catheter, parenteral nutrition, haematological and gynaecological malignancy, and receipt of ß-lactam/ß-lactamase inhibitors. Vital signs and laboratory values associated with candidaemia included elevated heart rate, temperature and creatinine, along with neutropenia and neutrophilia. Factors that demonstrated a decreased risk of candidaemia included diabetes mellitus, gastrostomy and urinary catheter with antibiotic use. The c-statistic was 0.741 (95% CI, 0.710-0.772). We identified a set of clinical characteristics that can predict the presence of candidaemia with candiduria.

Vitamin D-supplemented yogurt drink reduces Candida infections in a paediatric intensive care unit: a randomised, placebo-controlled clinical trial.

BACKGROUND: The prevalence of Candida infections in paediatric intensive care units (PICUs) has dramatically increased as a result of resistance to conventional anti-fungal treatments. Because vitamin D has been shown to exhibit fungicidal activity against Candida infection in an in vitro antimicrobial screening, we aimed to investigate the effect of vitamin D on Candida infections in the PICU. METHODS: Four hundred sixteen eligible children aged between 12 months to 5 years old admitted to the PICU, who were on broad-spectrum antibiotic therapy, participated in the study. Patients were randomly assigned to two study groups, receiving a plain yogurt drink (placebo group) or supplemented with 300 IU day-1 vitamin D (VD group). Primary outcome was defined as the incidences of Candida colonisation (Candida isolated from rectal swab) 14 days after enrollment. Secondary outcome measures were Candida growth in blood (candidaemia) and urine (candiduria). RESULTS: The prevalence of candiduria as well as candidaemia was significantly lower in the VD-treated group (26 cases) than in the placebo group (62 cases). The mean (SD) length of PICU stay was obviously lowered in the VD group [11.8 (1.2) days] compared to the placebo group [15.2 (2.3 days)], whereas cases of patient death were similar between the two groups. CONCLUSIONS: Supplementation of vitamin D effectively reduces infections of Candida in children who were critically ill and on broad-spectrum antibiotic treatment.

Zinc supplementation reduces Candida infections in pediatric intensive care unit: a randomized placebo-controlled clinical trial.

Resistance to anti-fungal drugs has become the main cause for increasing incidence rate of Candida infections in pediatric intensive care units (PICU). Zinc supplementation has been shown to exhibit beneficial effects on many pediatric illnesses. This study aimed to investigate the efficacy of zinc supplementation on prevalence of candidemia and candiduria infections in PICU. 724 eligible children between 1 to 5 years old admitted in PICU were randomly assigned into either zinc supplementation group or placebo group. Primary endpoints were the number of Candida infections, length of PICU stay and cases of patient death 14 days after enrollment. Secondary endpoints were the incidence rates of candidemia and candiduria. The incidences of candiduria and candidemia were significantly lower in the zinc group than the placebo group. The length of PICU stay and cases of patient death were obviously lowered in the zinc group compared to the placebo group. In conclusion, zinc supplementation shows beneficial clinical efficacy in reducing Candida infections among PICU patients on broad-spectrum antibiotics with critical illnesses.

Determination of antimicotic susceptibility pattern of Candida species isolated from patients with symptomatic candiduria.

BACKGROUND: The present study was conducted to determine antimicotic susceptibility of Candida species (sp.) from patients with symptomatic candiduria. MATERIALS AND METHODS: Identification of Candida sp. and determination of efficacy of most routine antifungals were done using polymerase chain reaction-restriction fragment length polymorphism method and E-test, respectively. RESULTS: The results from susceptibility test reveal that caspofungin and amphotericin B have high antifungal activity against both albicans (100% and 96%, respectively) and nonalbicans (95.11% and 72.72%, respectively) isolates. CONCLUSION: The present study suggests that caspofungin and amphotericin B have the excellent ability to eradicate both Candida groups that showed decreased susceptibility to other compounds.

Candiduria in kidney transplant recipients: Is antifungal therapy useful?

A French single-centre retrospective study between 2010 and 2014 was undertaken to assess candiduria's incidence in kidney transplant recipients (KTR), and the use and impact of antifungal treatment on outcome. Candiduria was defined as a urine culture with ≥103  cfu/mL of Candida species. Candiduria clearance, severe complications and death rates were estimated by Kaplan-Meier methods and the effect of treatment by Cox models. 52/1223 (4.3%) KTR had ≥1 episode of candiduria, 42 (81%) were females, 18 (35%) had diabetes, with an incidence of 2.3/100 person-year of follow-up. Candiduria was asymptomatic in 51 (98%) patients. Candida glabrata was the most frequent pathogen identified. Overall fungal clearance rate was 89%. Antifungal therapy was initiated in only 14 episodes (12%), according to guidelines. Three patients (6%) developed severe complications in the first 2 weeks after transplantation, and 8 (15%) died. Antifungal treatment had no impact on candiduria clearance (HR, 0.6; 95% CI, 0.3-1.1; P = .10), on recurrence rate (HR, 0.5; 95% CI, 0.1-2.3; P = .41) and on the risk of severe complications or death (HR, 1.1; 95% CI, 0.3-4.8; P = .89). Candiduria is rare and usually asymptomatic among KTR. Candiduria management in the immediate post-transplant period deserves careful attention.