Krusei Infection Research Articles

Molecular typing and antifungal susceptibility profile of Candida krusei bloodstream isolates from Türkiye.

Candida krusei also known as Pichia kudriavzevii is a potentially multidrug-resistant yeast because it is intrinsically resistant to fluconazole and develops acquired resistance to echinocandins and polyenes. Here, we aim to provide a better understanding of the epidemiology and transmission modes of C. krusei infections by comparing invasive bloodstream (n=35) and non-invasive vaginal (n=20) C. krusei isolates. The genetic relatedness of the isolates was assessed using a newly described short tandem repeat (STR) analysis and their sensitivity to eight antifungal compounds was evaluated by antifungal susceptibility testing using the CLSI microbroth dilution method. All C. krusei isolates revealed unique STR genotypes, indicating the absence of clonal transmission in the study group. Furthermore, no drug-resistant or non-wild-type isolates were identified. Our findings demonstrated high resolution of STR genotyping for the detection and simultaneous genetic analysis of multiple C. krusei strains in clinical samples and excellent in vitro activity of common antifungal agents against invasive strains.

Ophthalmologic Examination and Echocardiography Should be the Essential Components of Candidemia Bundle.

Candidemia is the most common form of invasive candidiasis, and it is associated with end-organ involvement, prolonged hospitalization, increased mortality, and higher healthcare costs. Candidemia can lead to metastatic heart and ocular infections. This study aimed to define the incidence, characteristics, and mortality of candidemia episodes and compare the data with our center's previous results. In this single-center retrospective observational study, we enrolled 250 patients over 18 years diagnosed with candidemia between January 2015 and December 2020. We obtained patients' demographic, clinical, laboratory, and therapeutic data from medical records. An ophthalmologic examination and screening with echocardiography were carried out within the first week after candidemia diagnosis. There were 275 candidemia episodes from 250 patients. The incidence of candidemia was 2.8/1000 admissions and 5.68/ 10,000 inpatient days, higher than our previous results (1.23/1000 and 3.29/10,000). The median age was 65 (interquartile range [IQR]=52-75) years. Malignancies were the most frequent comorbidity (50%). The most common type was Candida albicans (n=115, 41.8%). Candida glabrata (n=61, 22.2%) was common, particularly in surgical patients, patients with malignancy, and critically ill patients. There was Infectious disease consultation in 93.3% (257) episodes.The ophthalmoscopic examination was made in 145 episodes (52.7%), and ophthalmitis was detected in 16 (11.0%). Echocardiography was performed in 139 (50.5%) episodes; one case had an endocarditis diagnosis. The 30-day mortality was 44.7% (n=123). Mortality rates in C. glabrata and Candida krusei infections were higher (54.1% and 66.7). The factors related to mortality were intensive care unit requirement (p=0.0001), chronic liver disease (p=0.005), corticosteroid usage (p=0.0001), previous antibiotic usage (p=0.013), multiple antibiotic usage ( p=0.020), and CVC related candidemia (p=0.010). Because of the life-threatening complications such as endocarditis, increased mortality rates, and higher healthcare costs, systematic and comprehensive candidemia bundle applications would be effective strategies for providing an effective antifungal stewardship program.

Voriconazole Associated Hypertension: A Case Report

Objective: The study report a case of a young female with candida tropicalis and candida krusei infection who developed severe hypertension after she had repeated received voriconazole for few days.
 Case Presentation: A 23-year-old female was admitted to hospital because of recurrent urinary tract infection. She underwent horseshoe nephrectomy, extracorporeal lithotripsy treatment and double J-tube placement in the past 5 years. After multiple surgeries, she developed recurring fungal urinary tract infections and underwent anti-infective treatment. Twenty days ago, the patient developed chills, fever, dizziness, fatigue, urinary tract irritation signs and bilateral low back pain. Urine culture suggests Candida croco (resistant to fluconazole). After taking antifungal therapy with voriconazole 300 mg q12h, the patient experienced an unexplained increased blood pressure and transient loss of consciousness.
 The patient began to experience an increase in blood pressure (140-160/90-100 mmHg) on the second day of voriconazole treatment. After 5 days of taking voriconazole, the patient developed fatigue, dizziness and blurred vision with persistent hypertension (150/100 mmHg), and temporary loss of consciousness and syncope on day8, when blood pressure was measured at 175/95 mmHg.
 Conclusion: This case illustrates that acute blood pressure elevation may manifest in patients taking normal doses of voriconazole, which deserves the attention of clinicians.

Recombinant polymerase amplification combined with lateral flow strips for the detection of deep-seated Candida krusei infections

The incidence of Candida infections in intensive care units (ICU) has significantly increased in recent years, and these infections have become one of the most serious complications threatening the lives of ICU patients. The proportion of non-Candida albicans infections, such as Candida krusei and Candida glabrata infections, which are resistant to fluconazole, is increasing each year. Early identification of the strains causing Candida infections is important for the timely implementation of targeted treatments to save patients’ lives. However, the current methods of direct microscopy, culture, and histopathology, as well as other diagnostic methods, have many shortcomings, such as their low sensitivity and long assay times; therefore, they cannot meet the needs for early clinical diagnosis. Recombinant polymerase amplification (RPA) is a promising isothermal amplification technique that can be performed without sophisticated instruments and equipment, and is suitable for use in resource-poor areas. RPA combined with lateral flow strips (LFS) can be used to rapidly amplify and visualize target genes within 20 min. In this study, RPA-LFS was used to amplify the internal transcribed spacer 2 (ITS2) region of C. krusei. The primer-probe design was optimized by introduction of base mismatches (probe modification of five bases) to obtain a specific and sensitive primer-probe combination for the detection of clinical specimens. Thirty-five common clinical pathogens were tested with RPA-LFS to determine the specificity of the detection system. The RPA-LFS system specifically detected C. krusei without cross-reaction with other fungi or bacteria. A gradient dilution of the template was tested to explore the lower limit of detection and sensitivity of the assay. The sensitivity was 10 CFU/50 µL per reaction, without interference from genomic DNA of other species. The RPA-LFS and qPCR assays were performed on 189 clinical specimens to evaluate the detection performance of the RPA-LFS system. Seventy-six specimens were identified as C. krusei, indicating a detection rate of 40.2%. The results were consistent with those of qPCR and conventional culture methods. The RPA-LFS system established in our study provides a reliable molecular diagnostic method for the detection of C. krusei, thus meeting the urgent need for rapid, specific, sensitive, and portable clinical field testing.

Talus osteomyelitis by Candida krusei with multiple huge cystic lesions: a case report and review of literatures

BackgroundOsteomyelitis due to Candida krusei are extremely rare, given that only six cases have been reported, all of which are limited to the patients with immunocompromising risk factors. Here we report a case of C. krusei osteomyelitis in an immunocompetent patient, presenting with multiple huge cystic lesions of talus.Case presentationA 66-year-old female presented with one year history of painful swelling of right ankle and a draining sinus around lateral malleolus. Five months and three months ago, she had undergone arthroscopic synovectomy and bursectomy which revealed no causative organism. Open bursectomy with sinus tract excision was performed and intravenous antibiotic was administered. Two year after the surgery, the patient revisited the clinic for recurrent painful swelling with pus drainage at the same location. Multiple huge cystic lesions with osteolysis and sclerotic rim of talus were found and C. krusei was isolated from tissue culture. The patient received surgical debridement and prolonged antifungal treatment comprising caspofungin and voriconazole.ConclusionsIn this case, C. krusei infection showed atypically aggressive osteolysis shown as multiple huge cystic abscess. High index of suspicion is critical for early diagnosis and treatment to prevent such devastating results even in an immunocompetent patient.

Diphenyl diselenide suppresses key virulence factors of Candida krusei, a neglected fungal pathogen

Candida krusei is a candidiasis etiological agent of relevance in the clinical setting because of its intrinsic resistance to fluconazole. Also, it has opened up new paths in the area of alternative therapeutic techniques. This project demonstrated the effects of diphenyl diselenide (PhSe)2 and p-cloro diphenyl diselenide (pCl-PhSe)2, two organochalcogen compounds, on relevant virulence factors for the early stage of the C. krusei host interaction and infection process. Both compounds inhibited adherence of C. krusei to both polystyrene surfaces and cervical epithelial cells and biofilm formation; the structure of the biofilm was also changed in a dose-dependent manner. In addition, both compounds inhibited C. krusei growth, but (PhSe)2 significantly increased the time duration of the lag phase and delayed the start of the exponential phase in growth kinetics. (PhSe)2 has more potential antifungal activity than (pCl-PhSe)2 in inhibiting the adherence to epithelial cells, biofilm formation, and growth of C. krusei.

Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis.

Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.

Potential antifungal impact of citral and linalool administered individually or combined with fluconazole against clinical isolates of Candida krusei

Introduction: Candida krusei is recognized as a major fungal pathogen in patients with immunodeficiency disorders. The present study aimed at investigating the anticandidal activities of citral and linalool combined with fluconazole (FLZ) against FLZ-resistant C. krusei strains. Methods: Antifungal activities were evaluated by the broth microdilution (MD) method to determine the minimum inhibitory and fungicidal concentrations (namely, MICs and MFCs) according to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 document. The interactions were further evaluated using fractional inhibitory concentration indices (FICIs) for combinations of citral+FLZ and linalool+FLZ, calculated from checkerboard MD assays. Results: The mean ± standard deviation (SD) MIC values of citral, linalool, and FLZ against the C. krusei isolates were 70.23 ± 17, 150 ± 38.73, and 74.66 ± 36.95 μg/mL, respectively. Some fungicidal activities were also observed for citral (2.5) and linalool (1.53) against the C. krusei isolates. The FICI values of citral+FLZ and linalool+FLZ for the C. krusei isolates ranged from 0.4 to 1.00 and 0.19 to 0.63, respectively. The additive and synergistic interactions of linalool + FLZ were further observed in 12 (57.1%) and 9 (42.9%) C. krusei isolates. However, there was an additive interaction for citral + FLZ in 17 (80.9%) isolates. They also showed a synergistic interaction in only four (19.1%) isolates. Moreover, linalool and citral plus FLZ did not have any antagonistic effect on any isolates. Conclusion: The study findings support the possible capabilities of citral and linalool, as anticandidal agents, and FLZ might be supplemented with citral and/or linalool for treating FLZ-resistant C. krusei infections.

A Subcutaneous Abscess Caused by Candida Krusei Infection: A rare Manifestation

Candida is considered a normal microbiota of the gastrointestinal and genitourinary systems with a tendency for an invasive disease if the predisposing conditions exist. Mucocutaneous manifestations of Candida infection include the commonly encountered oropharyngeal thrush, vulvovaginitis, balanitis, intertrigo, paronychia, diaper dermatitis, and the rare chronic mucocutaneous candidiasis. Subcutaneous abscess due to Candida (albicans and non-albicans) is rare, with the literature available only in case reports. We report the first case of a subcutaneous perineal abscess due to C. krusie in a patient with poorly controlled diabetes without immune compromised conditions or a hematologic malignancy.

In-vitro pharmacokinetic/pharmacodynamic model data suggest a potential role of new formulations of posaconazole against Candida krusei but not Candida glabrata infections

Posaconazole exhibits in-vitro activity against Candida glabrata and Candida krusei. Epidemiological cut-off values set by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory Standards Institute (CLSI) are 1/1 and 0.5/0.5 mg/L, respectively, but clinical breakpoints have not been established to date. This study explored the pharmacodynamics (PD) of posaconazole in a validated one-compartment in-vitro pharmacokinetic (PK)/PD model, and determined the probability of PK/PD target attainment (PTA) for the available formulations. Five C. glabrata and three C. krusei isolates with posaconazole minimum inhibitory concentrations (MICs) of 0.06-2 and 0.03-0.25 mg/L, respectively, were tested in the PK/PD model simulating different time-concentration profiles of posaconazole. The exposure-effect relationship fAUC0-24/MIC was described for EUCAST/CLSI methods, and PTA was calculated in order to determine PK/PD susceptibility breakpoints for oral solution (400 mg q12h), and intravenous (i.v.)/tablet formulations (300 mg q24h). Fungicidal activity (~2log kill) was found against the most susceptible C. glabrata isolate alone, and against all three C. krusei isolates. The corresponding EUCAST/CLSI PK/PD targets (fAUC0-24/MIC) were 102/79 for C. glabrata and 12/8 for C. krusei. Mean PTA was high (>95%) for C. glabrata isolates with EUCAST/CLSI MICs ≤0.03/≤0.03 mg/L for oral solution and ≤0.125/≤0.125 mg/L for i.v. and tablet formulations for the wild-type population. For C. krusei isolates, mean PTA was high (>95%) for EUCAST/CLSI MICs ≤0.25/≤0.5 mg/L for oral solution and ≤1/≤2 mg/L for i.v. and tablet formulations for the wild-type population. The use of posaconazole to treat C. glabrata infections is questionable. Intravenous and tablet formulations may be therapeutic options for the treatment of C. krusei infections, and oral exposure can be optimized with therapeutic drug monitoring (trough levels >0.6-0.9 mg/L).

Interaction Between Dendritic Cells and Candida krusei β-Glucan Partially Depends on Dectin-1 and It Promotes High IL-10 Production by T Cells.

Host-Candida interaction has been broadly studied during Candida albicans infection, with a progressive shift in focus toward non-albicans Candida species. C. krusei is an emerging multidrug resistant pathogen causing rising morbidity and mortality worldwide. Therefore, understanding the interplay between the host immune system and C. krusei is critically important. Candia cell wall β-glucans play significant roles in the induction of host protective immune responses. However, it remains unclear how C. krusei β-glucan impacts dendritic cell (DC) responses. In this study, we investigated DC maturation and function in response to β-glucans isolated from the cell walls of C. albicans, C. tropicalis, and C. krusei. These three distinct Candida β-glucans had differential effects on expression of the DC marker, CD11c, and on DC maturation. Furthermore, bone-marrow derived DCs (BMDCs) showed enhanced cytokine responses characterized by substantial interleukin (IL)-10 production following C. krusei β-glucan stimulation. BMDCs stimulated with C. krusei β-glucan augmented IL-10 production by T cells in tandem with increased IL-10 production by BMDCs. Inhibition of dectin-1 ligation demonstrated that the interactions between dectin-1 on DCs and cell wall β-glucans varied depending on the Candida species. The effects of C. krusei β-glucan were partially dependent on dectin-1, and this dependence, in part, led to distinct DC responses. Our study provides new insights into immune regulation by C. krusei cell wall components. These data may be of use in the development of new clinical approaches for treatment of patients with C. krusei infection.

1157. Clinical Safety, Efficacy, and Pharmacokinetics of Fosmanogepix, a Novel First-in-class Antifungal, in Patients with Renal Insufficiency: Subset Analysis from a Phase 2 Candidemia Trial

BackgroundFosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, and broad-spectrum activity against yeasts and molds, including fungi resistant to other antifungal agents. Patients with candidemia often have underlying renal insufficiency or are receiving medications that affect renal function. This analysis evaluated outcomes in patients with varying degrees of renal insufficiency.MethodsThis global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp within 96 hrs prior to study entry with ≤ 2 days of prior antifungal treatment were eligible, including those with renal insufficiency. Patients with neutropenia, C. krusei infection, deep-seated Candida infections or receiving hemodialysis were excluded. Subjects were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Patients requiring antifungal treatment beyond 14 days received fluconazole. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee. Successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment.Results14/21 (66%) subjects had some degree of renal insufficiency: 7 had mild renal insufficiency (GFR:60-89), 5 had moderate renal insufficiency (GFR:30-59), and 2 had severe renal insufficiency (GFR:15-29). 12/14 (86%) completed study treatment, and treatment was successful at EOST in 12/14 (86%) subjects. Decline in renal function was not observed at EOST. 4 had worsening of renal function during the follow-up period; none required dialysis. Renal impairment did not increase exposure of FMGX. There were no treatment-related adverse events.ConclusionFMGX demonstrated high level treatment success with no evidence of drug-related nephrotoxicity, with no dose adjustments required. These preliminary data support the continued evaluation of FMGX in patients with candidemia and renal dysfunction as an alternative to potentially nephrotoxic antifungal agents.Disclosures Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

147. Clinical Safety and Efficacy of Novel Antifungal, Fosmanogepix, in the Treatment of Candidemia: Results from a Phase 2 Proof of Concept Trial

BackgroundFosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, that has broad-spectrum activity against both yeasts, molds, and dimorphic fungi, including fungi resistant to other antifungal agents. FMGX has a favorable safety profile, reduced potential for clinically significant drug-drug interactions, and is formulated for IV and oral administration.MethodsThis global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp. within 96 hrs prior to study entry, with ≤2 days of prior antifungal treatment were eligible. Patients with neutropenia, C. krusei infection, or deep-seated Candida infections were excluded. Patients were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Short-term fluconazole (or appropriate alternative) could follow if treatment was required beyond 14 days. Patients with a diagnosis of candidemia within 96 hrs of start of study drug who received at least 1 dose of FMGX were included in the mITT population. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee (DRC). Successful outcome was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at EOST. All Candida isolates were tested for antifungal susceptibility.ResultsA total of 21 subjects were enrolled in the study: 20 were included in the mITT. Median duration of FMGX was 11 days (range 5–14). All subjects received IV FMGX, 48% (10/21) received PO FMGX. The DRC-assessed success rate at EOST was 80% (16/20). Survival at day 30 was 85% (17/20); 3 deaths were not related FMGX. FMGX was well-tolerated with no treatment-related serious adverse events or discontinuations. FMGX had potent in vitro activity against all study Candida spp. (EUCAST MIC range 0.001–0.03 µg/ml) including those resistant to other antifungal agents.ConclusionFMGX was safe, well-tolerated, and demonstrated proof of concept with a high level of treatment success in patients with candidemia.Disclosures Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Ricard Ferrer, MD, PhD, Shionogi B.V. (Advisor or Review Panel member) Todd P. McCarty, MD, Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Iwonka Oborska, PhD, Amplyx Pharmaceuticals (Consultant, Independent Contractor) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

A seven-year surveillance of Candida bloodstream infection at a university hospital in KSA

ObjectivesCandidemia incidence has increased in the past few years, with high mortality. Previous studies have reported a variable distribution of Candida spp. among different regions. This study aimed to identify the species found in Candida bloodstream infections, routine antifungal susceptibility testing, and mortality outcomes in an academic medical centre. MethodsBetween January 2012 and December 2018, the positive blood cultures for candidemia infection were retrieved and statistically analysed for species prevalence, susceptibility pattern, and crude mortality at 14, 30, 60 and 90 days. ResultsOf 156 candidemia cases, a majority (69.2%) was caused by non-albicans Candida spp. After Candida albicans (30.8%), Candida tropicalis and Candida parapsilosis were the second and third most frequeunt isolates spp, each counting for 23.7%. Acquired resistance was detected in 14.8% of candidemia strains. No other antifungal resistance was detected. The overall crude mortality rates of all species were 29.3%, 47.9%, 56.4%, and 58.0% at 14, 30, 60, and 90 days, respectively. A higher mortality rate was noted in cases of Candida krusei infection (crude mortality 71.4–100%, p = 0.002). ConclusionIn this study, a considerable shift to non-albicans Candida causing most bloodstream infections was observed. As such infections pose a serious threat to hospitalised patients, microbiology laboratories are urged to adopt rapid diagnostic and minimal inhibitory concentration-based testing for the detection of susceptible dose-dependent phenotypes. Prospective studies are essential to consider the prognosis of bloodstream infections by various Candida species in a multivariate model.

Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis.

Candidaemia is an important infectious complication for haematological malignancy patients. Antifungal prophylaxis reduces the incidence of candidaemia but may be associated with breakthrough candidaemia. To analyse the Candida species' distribution and relative antifungal susceptibility profiles of candidaemia episodes in relation to the use of antifungal prophylaxis among Italian SEIFEM haematology centres. This multicentre retrospective observational SEIFEM study included 133 single-species candidaemia episodes of haematological malignancy patients for whom antifungal susceptibility testing results of blood Candida isolates were available between 2011 and 2015. Each participating centre provided both clinical and microbiological data. Non-Candida albicans Candida (NCAC) species were the mostly isolated species (89, 66.9%), which accounted for Cparapsilosis (35, 26.3%), Cglabrata (16, 12.0%), Ckrusei (14, 10.5%), Ctropicalis (13, 9.8%) and uncommon species (11, 8.3%). Calbicans caused the remaining 44 (33.1%) episodes. Excluding 2 Calbicans isolates, 23 of 25 fluconazole-resistant isolates were NCAC species (14 Ckrusei, 6 Cglabrata, 2 Cparapsilosis and 1 Ctropicalis). Fifty-six (42.1%) of 133 patients developed breakthrough candidaemia. Systemic antifungal prophylaxis consisted of azoles, especially fluconazole and posaconazole, in 50 (89.3%) of 56 patients in whom a breakthrough candidaemia occurred. Interestingly, all these patients tended to develop a Ckrusei infection (10/56, P=.02) or a fluconazole-resistant isolate's infection (14/50, P=.04) compared to patients (4/77 and 10/77, respectively) who did not have a breakthrough candidaemia. Optimisation of prophylactic strategies is necessary to limit the occurrence of breakthrough candidaemia and, importantly, the emergence of fluconazole-resistant NCAC isolates' infections in haematological malignancy patients.

Candida krusei Infection in an Acute Lymphocytic Leukaemia Patient: A Case Report

Candida krusei Infection in an Acute Lymphocytic Leukaemia Patient: A Case Report

Enhanced Killing of Candida krusei by Polymorphonuclear Leucocytes in the Presence of Subinhibitory Concentrations of Melaleuca alternifolia and "Mentha of Pancalieri" Essential Oils.

The aim of this study was to evaluate the influence of tea tree oil (TTO) and “Mentha of Pancalieri” essential oil (MPP) on intracellular killing of Candida krusei, often resistant to conventional drugs, by polymorphonuclear leucocytes (PMNs). Intracellular killing was investigated by incubating yeasts and PMNs with essential oils (EOs) at 1/4 and 1/8 × MIC (Minimal Inhibitory Concentration), in comparison with anidulafungin, used as a reference drug. Killing values were expressed as Survival Index (SI) values. The cytotoxicity of EOs was evaluated by 3-[4,-5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Both EOs were more efficaceous at 1/8 × MIC than 1/4 × MIC, with killing values higher than observed in EO-free systems and in presence of anidulafungin, indicating that the decreasing concentrations did not cause lower candidacidal activity. This better activity at 1/8 × MIC is probably due to the EOs’ toxicity at 1/4 × MIC, suggesting that at higher concentrations EOs might interfere with PMNs functionality. TTO and MPP at 1/8 × MIC significantly increased intracellular killing by PMNs through their direct action on the yeasts (both EOs) or on phagocytic cells (MPP), suggesting a positive interaction between EOs and PMNs to eradicate intracellular C. krusei. These data showed a promising potential application of TTO and “Mentha of Pancalieri” EO as natural adjuvants in C. krusei infection management.

Emergence of Vulvovaginal Candidiasis among Lebanese Pregnant Women: Prevalence, Risk Factors, and Species Distribution.

Objective Candida species colonize the vagina in at least 20% of women, with rates rising to 30% during pregnancy. This study aimed at determining the prevalence and risk factors of vulvovaginal candidiasis (VVC) in pregnant women at 35-37 weeks of gestation. It also aims at finding possible correlations between VVC and vaginal colonization by other agents, such as Group B Streptococcus (GBS) and bacterial vaginosis. Methodology Over a one-year period, high vaginal swabs were collected from pregnant women during their regular antenatal checkup in different polyclinics in Beirut and South Lebanon. Swabs were examined microscopically, cultured on Sabouraud Dextrose Agar, and Candida isolates were identified using Chromatic Candida medium and Germ Tube Test. Results VVC was detected in 44.8% of samples, with C. glabrata (44.4%) and C. albicans (43.4%) being the most isolated species. Approximately, half of pregnant women (57.7%) were coinfected with Candida and bacterial vaginosis, while 26% of them carried simultaneously Candida spp. and GBS. No significant correlation was found between the occurrence of VVC and demographic, clinical, medical, and reproductive health characteristics of pregnant women. In contrast, participants with previous miscarriages and those being hospitalized during the past 12 months were more susceptible to develop vaginal C. krusei infection in comparison to other Candida species (p=0.0316 and p=0.0042, respectively). Conclusion The prevalence of VVC in pregnant women is an increasing trend in our community. Therefore, routine medical examination and regular screening for candidiasis in the antenatal care program is highly recommended to manage the disease and its complications.

Population genomics shows no distinction between pathogenic Candida krusei and environmental Pichia kudriavzevii: One species, four names.

We investigated genomic diversity of a yeast species that is both an opportunistic pathogen and an important industrial yeast. Under the name Candida krusei, it is responsible for about 2% of yeast infections caused by Candida species in humans. Bloodstream infections with C. krusei are problematic because most isolates are fluconazole-resistant. Under the names Pichia kudriavzevii, Issatchenkia orientalis and Candida glycerinogenes, the same yeast, including genetically modified strains, is used for industrial-scale production of glycerol and succinate. It is also used to make some fermented foods. Here, we sequenced the type strains of C. krusei (CBS573T) and P. kudriavzevii (CBS5147T), as well as 30 other clinical and environmental isolates. Our results show conclusively that they are the same species, with collinear genomes 99.6% identical in DNA sequence. Phylogenetic analysis of SNPs does not segregate clinical and environmental isolates into separate clades, suggesting that C. krusei infections are frequently acquired from the environment. Reduced resistance of strains to fluconazole correlates with the presence of one gene instead of two at the ABC11-ABC1 tandem locus. Most isolates are diploid, but one-quarter are triploid. Loss of heterozygosity is common, including at the mating-type locus. Our PacBio/Illumina assembly of the 10.8 Mb CBS573T genome is resolved into 5 complete chromosomes, and was annotated using RNAseq support. Each of the 5 centromeres is a 35 kb gene desert containing a large inverted repeat. This species is a member of the genus Pichia and family Pichiaceae (the methylotrophic yeasts clade), and so is only distantly related to other pathogenic Candida species.

Poor in vivo efficacy of caspofungin, micafungin and amphotericin B against wild-type Candida krusei clinical isolates does not correlate with in vitro susceptibility results

We determined micafungin, caspofungin and amphotericin B (AMB) minimum inhibitory concentration (MICs) and killing rates in RPMI-1640 and in RPMI-1640 with 50% serum against three Candida krusei bloodstream isolates. MIC ranges in RPMI-1640 were 0.125–0.25, 0.25 and 0.125–0.5 mg/L, in RPMI-1640 with 50% serum, MICs were 64–128-, 8- and 4–16-fold higher, respectively. In RPMI-1640 micafungin and caspofungin at 1, 4, 16 and 32 mg/L as well as AMB at 2 mg/L were fungicidal against all isolates in ≤3.96, ≤4.42 and 14.96 h, respectively. In RPMI-1640 with 50% serum, caspofungin was fungicidal for all isolates only at 32 mg/L, micafungin and AMB were fungistatic. In neutropenic mice, 5 mg/kg caspofungin and 1 mg/kg AMB were ineffective against two of the three isolates. Thus, in vivo efficacy of echinocandins and AMB is weak or absent against C. krusei. Prescribers treating C. krusei infections with echinocandins should watch out for clinical resistance and therapeutic failure.