Fungemia by Wickerhamomyces anomalus-A Narrative Review.

Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, suggesting that this microorganism is an emerging pathogen. The present review aimed to provide data on the epidemiology, antifungal resistance, clinical characteristics, treatment, and outcomes of fungemia by W. anomalus by extracting all the available information from published original reports in the literature. PubMed/Medline, Cochrane Library, and Scopus databases were searched for eligible articles reporting data on patients with this disease. In total, 36 studies involving 170 patients were included. The age of patients with fungemia by W. anomalus ranged from 0 to 89 years; the mean age was 22.8 years, the median age was 2.2 years, with more than 37 patients being less than one month old, and 54% (88 out of 163 patients) were male. Regarding patients' history, 70.4% had a central venous catheter use (CVC), 28.7% were on total parenteral nutrition (TPN), 97% of neonates were hospitalized in the neonatal ICU (NICU), and 39.4% of the rest of the patients were hospitalized in the intensive care unit (ICU). Previous antimicrobial use was noted in 65.9% of patients. The most common identification method was the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 34.1%, VITEK and VITEK 2 in 20.6%, and ID32 C in 15.3%. W. anomalus had minimal antifungal resistance to fluconazole, echinocandins, and amphotericin B, the most commonly used antifungals for treatment. Fever and sepsis were the most common clinical presentation noted in 95.8% and 86%, respectively. Overall mortality was 20% and was slightly higher in patients older than one year. Due to the rarity of this disease, future multicenter studies should be performed to adequately characterize patients' characteristics, treatment, and outcomes, which will increase our understanding and allow drawing safer conclusions regarding optimal management.

Fungemia With Wickerhamomyces anomalus: A Case Report and Literature Review.

We report the case of an 84-year-old man with a history of IgG4-related sclerosing cholangitis who was diagnosed with advanced esophageal cancer and underwent radiation and chemotherapy. An implantable central venous access port was placed for chemotherapy and total parenteral nutrition. The patient presented with a fever and received antimicrobial therapy for acute cholangitis but remained febrile, and subsequently, yeast was detected in the aerobic bottle of blood culture obtained from the central venous line. The yeast was identified as Wickerhamomyces anomalus. Liposomal amphotericin B was administered, and the central line access port was removed. After confirmation of negative blood cultures and 14 days post treatment, he underwent reinsertion of the central line access port. Due to persistent pain at the insertion site, fluconazole was added for an additional 14 days, and the patient was discharged and transferred to another hospital. Wickerhamomyces anomalus is a rare fungal infection with other synonyms including Pichia anomala, Hansenula anomala, and Candida pelliculosa. A literature review of 53 case reports of Wickerhamomyces anomalus, Pichia anomala, Hansenula anomala, and Candida pelliculosa was conducted, with a total of 211 cases reviewed. Fungemia was reported in 94% of cases, with central venous catheterization, parental feeding, low birth weight, and immunocompromised status identified as major risk factors. The majority of cases were pediatric, particularly neonatal, and there were reports of nosocomial infections causing outbreaks, with some cases involving the eye such as endophthalmitis or keratitis.

Application of Novel Short Tandem Repeat Typing for Wickerhamomyces anomalus Reveals Simultaneous Outbreaks within a Single Hospital.

Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.

Characterization of ß-glucosidase of Lactobacillus plantarum FSO1 and Candida pelliculosa L18 isolated from traditional fermented green olive.

BACKGROUND: Oleuropein, the main bitter phenolic glucoside responsible for green olive bitterness, may be degraded by the ß-glucosidase enzyme to release glucose and phenolic compounds. RESULTS: Lactobacillus plantarum FSO1 and Candida pelliculosa L18 strains, isolated from natural fermented green olives, were tested for their ß-glucosidase production and activity at different initial pH, NaCl concentrations, and temperature. The results showed that strains produced extracellular and induced ß-glucosidase, with a molecular weight of 60 kD. The strains demonstrated their biodegradation capacity of oleuropein, associated with the accumulation of hydroxytyrosol and other phenolic compounds, resulting in antioxidant activity values significantly higher than that of ascorbic acid. The highest production value of ß-glucosidase was 0.91 U/ml obtained at pH 5 and pH 6, respectively for L. plantarum FSO1 and C. pelliculosa L18. The increase of NaCl concentration, from 0 to 10% (w/v), inhibited the production of ß-glucosidase for both strains. However, the ß-glucosidase was activated with an increase of NaCl concentration, with a maximum activity obtained at 8% NaCl (w/v). The enzyme activity was optimal at pH 5 for both strains, while the optimum temperature was 45 °C for L. plantarum FSO1 and 35 °C for C. pelliculosa L18. CONCLUSIONS: L. plantarum FSO1 and C. pelliculosa L18 strains showed their ability to produce an extracellular and induced ß-glucosidase enzyme with promising traits for application in the biological processing of table olives.

Two different clones of Candida pelliculosa bloodstream infection in a tertiary neonatal intensive care unit.

INTRODUCTION: Fungemia in preterm infants results in high mortality and morbidity. The genotypes, drug susceptibilities of Candida pelliculosa strains, and clinical features of two outbreaks of neonatal candidemia caused by C. pelliculosa were analyzed, in order to provide evidence for the outbreaks and characteristics of C. pelliculosa neonatal candidemia. METHODOLOGY: The strains were genotyped by pulsed-field gel electrophoresis to investigate their genetic relatedness. The broth microdilution method was used to determine in vitro susceptibility of the isolates to antifungal drugs. Clinical features of the infected patients were collected to analyze the risks for C. pelliculosa infection. RESULTS: Fourteen neonates, hospitalized in the neonatal intensive care unit from November 2012 to October 2013, were infected by C. pelliculosa. All 14 patients were cured after treatment with fluconazole and discharged without any complications. The C. pelliculosa isolates from the 14 patients were clustered into two groups, indicating that the outbreaks were caused by two types of strains. Eight of nine strains isolated from the 2013 outbreak were clustered into the same group, while one isolate was grouped together with five isolates from the 2012 outbreak. In vitro experiments demonstrated high antifungal activity of fluconazole, voriconazole, amphotericin B, and 5-fluorocytosine to C. pelliculosa. The common symptoms of C. pelliculosa candidaemia were fever, cyanosis, polypnea, hypoactivity, and apnea. CONCLUSIONS: The current study revealed high in vitro susceptibility of C. pelliculosa to antifungals. As C. pelliculosa candidaemia cannot be characterized by clinical symptoms and routine blood testing alone, monitoring unusual strains isolated from immunodeficient hosts is very important to prevent possible outbreaks.

Risk factors and biofilm formation analyses of hospital-acquired infection of Candida pelliculosa in a neonatal intensive care unit.

BACKGROUND: Candida pelliculosa is an ecological fungal species that can cause infections in immunocompromised individuals. Numerous studies globally have shown that C. pelliculosa infects neonates. An outbreak recently occurred in our neonatal intensive care unit; therefore, we aimed to evaluate the risk factors in this hospital-acquired fungal infection. METHODS: We performed a case-control study, analysing the potential risk factors for neonatal infections of C. pelliculosa so that infection prevention and control could be implemented in our units. Isolated strains were tested for drug resistance and biofilm formation, important factors for fungal transmission that give rise to hospital-acquired infections. RESULTS: The use of three or more broad-spectrum antimicrobials or long hospital stays were associated with higher likelihoods of infection with C. pelliculosa. The fungus was not identified on the hands of healthcare workers or in the environment. All fungal isolates were susceptible to anti-fungal medications, and after anti-fungal treatment, all infected patients recovered. Strict infection prevention and control procedures efficiently suppressed infection transmission. Intact adhesin-encoding genes, shown by genome analysis, indicated possible routes for fungal transmission. CONCLUSIONS: The use of three or more broad-spectrum antimicrobials or a lengthy hospital stay is theoretically associated with the risk of infection with C. pelliculosa. Strains that we isolated are susceptible to anti-fungal medications, and these were eliminated by treating all patients with an antifungal. Transmission is likely via adhesion to the cell surface and biofilm formation.

Candida pelliculosa sepsis in a neonate: a case report.

Candida pelliculosa is a rare fungal cause of neonatal sepsis. Premature and very low birthweight infants are at especially high risk of neonatal fungal infections. There have been no reports of C. pelliculosa infection in Anhui Province, China. Here, we report a case of C. pelliculosa fungemia in a newborn boy admitted 30 minutes after delivery with grunting, cyanosis, and asphyxia. C. pelliculosa was identified as the causative organism using blood culture, DNA sequencing, and mass spectrometric analysis. After 20 days of fluconazole therapy, the patient's symptoms stabilized. Together with other relevant literature, this report provides evidence that premature neonates are at increased risk of fungal infections and that C. pelliculosa fungemia should be diagnosed early using blood cultures to enable effective treatment. Fluconazole may be effective for treating neonates with C. pelliculosa infection.

Investigation and control of outbreaks of Candida Pelliculosa catheter-related bloodstream infection in the neurosurgical intensive care unit / 中国基层医药

Objective:To investigate the causes of the outbreak of Candida Pelliculosa catheter-related bloodstream infection in the neurosurgical intensive care unit (ICU), find out the source of infection and the route of transmission, and provide evidence for the prevention and control of nosocomial infection. Methods:An epidemiological investigation and environmental hygiene monitoring were made in patients with Candida Pelliculosa catheter-related bloodstream infection who received treatment in March and April 2019 in Houma People's Hospital, China. Comprehensive measures were taken to control the outbreaks of Candida Pelliculosa catheter-related bloodstream infection. Results:There were four patients with Candida Pelliculosa catheter-related bloodstream infection in the ICU of Neurosurgery Department of Houma People's Hospital, China. Eight samples were collected from these four patients. Ten strains were isolated and identified positive for Candida Pelliculosa. Drug sensitivity test revealed identical results: the minimum inhibitory concentration (MIC) of 5-fluorocytosine, amphotericin B, fluconazole, itraconazole and voriconazole was ≤ 4 mg/L, ≤ 0.5 mg/L, < 1 mg/L, ≤ 0.12 mg/L and ≤ 0.06 mg/L, respectively. No target bacteria were detected from the environment. Candida Pelliculosa infection was not observed after taking comprehensive control measures such as strengthening hand hygiene supervision in medical staff and thorough disinfection of the environment. Conclusion:Poor hand hygiene compliance in medical staff in neurosurgical ICU and non-sufficient environmental disinfection may be the main causes for the outbreak of Candida Pelliculosa catheter-related bloodstream infection.

Investigation of a nosocomial outbreak of fungemia caused by Candida pelliculosa (Pichia anomala) in a Korean tertiary care center.

BACKGROUND: Candida pelliculosa is a rare pathogen of fungemia. There have been a few nosocomial outbreaks of C. pelliculosa fungemia in nurseries and pediatric intensive care units (ICU), hematologic units, and surgical ICU. We describe an epidemiologic outbreak investigation, including case findings of C. pelliculosa fungemia in South Korea. METHODS: This outbreak investigation conducted in a 940-bed, tertiary referral center, Ulsan, South Korea and included active microbial surveillance and a case-control study. RESULTS: A patient in the trauma intensive care unit (ICU) with multiple trauma developed C. pelliculosa fungemia, and 10 patients in the trauma ICU, medical ICU, and 2 general wards subsequently contracted C. pelliculosa fungemia during the next 24 days (November 16 and December 9, 2015). The 16s rRNA sequencing of 4 isolates showed that C. pelliculosa was verified with 99-100% similarity (GenBank accession number: KF317892.1), and these isolates were identical in the randomly amplified polymorphic DNA (RAPD) assay. A case-control study showed that medical staff and staying in the interventional radiology procedure room were risk factor for development of C. pelliculosa fungemia. After intervention including strict hand washing, disinfecting medical equipment, and contact precautions, there have been no new C. pelliculosa infections since December 10, 2015. CONCLUSIONS: This is the first report of a nosocomial outbreak involving 11 patients in 2 ICUs and 2 general wards caused by C. pelliculosa in South Korea. Infection control measures are important for decreasing transmission of C. pelliculosa in the hospital.

Reporting an outbreak of Candida pelliculosa fungemia in a neonatal intensive care unit.

BACKGROUND: Fungemia in preterm infants is associated with high mortality and morbidity. This study reports an outbreak of unusual fungemia in a tertiary neonatal intensive care unit (NICU). METHODS: Ten Candida pelliculosa bloodstream isolates were identified from six infants hospitalized in the NICU from February to March 2009. Environmental study was performed, and genetic relatedness among the 10 clinical isolates of C pelliculosa and six control C pelliculosa strains was characterized by randomly amplified polymorphic DNA assay. In vitro susceptibility of isolates to six antifungal agents was analyzed by broth microdilution method. Amphotericin B was given to infected infants and prophylactic fluconazole was prescribed to the other noninfected extremely low birth weight infants during the outbreak. RESULTS: Thrombocytopenia (platelet counts <100×10(9)/L) was the early laboratory finding in four infants. One of six patients died, making overall mortality 17%. Fluconazole, voriconazole, amphotericin B, and micafungin provided good antifungal activity. Cultures from the environment and hands of caregivers were all negative. Molecular studies indicated the outbreak as caused by a single strain. The outbreak was controlled by strict hand washing, cohort infected patients, confined physicians and nurses to take care of patients, prophylactic fluconazole to uninfected neonates, and proper management of human milk. CONCLUSION: The study demonstrated the clinical importance of emerged non-albicans Candida species in NICU. For unusual pathogen isolated from immunocompromised hosts, more attention should be paid to monitor the possibility of an outbreak.

A Case of Candida pelliculosa Prosthetic Valve Endocarditis Treated with Anidulafungin and Valve Replacement / 감염과화학요법

Candida pelliculosa is a rare cause of human infection. In this report, we describe a case of infective endocarditis caused by C. pelliculosa in a patient with a prosthetic heart valve. A 72-year-old female presented with a complaint of blurred vision, which she had been experiencing over a period of four weeks. Transthroasic echocardiography showed vegetation on the prosthetic mitral valve. A blood culture isolate was confirmed as C. pelliculosa.

Candida en el departamento de neonatologia de la Maternidad "Concepción Palacios" enero-junio 2006 / Candida in the department of neonatalogy of the Maternity

En los últimos años la candidemia se ha incrementado en las centros hospitalarios, siendo las áreas de cuidados intensivos donde se observa con mayor frecuencia, ya que los pacientes presentan condiciones que favorecen la instauración de infecciones fúngicas. El objetivo de este estudio fue identificar y conocer la sensibilidad de las especies de Candida predominantes en el Departamento de Neonatología de la Maternidad “Concepción Palacios”. De 349 hemocultivos positivos recibidos del 01 de enero al 30 de junio del 2006; 74 (21.3%) desarrollaron Candida no albicans, con predominio de Candida pelliculosa, una levadura emergente involucrada como agente causal de fungemias, que presentó un patrón de sensibilidad variable.

In the last years the candidemia has increased in the hospital centers, being the areas of intensive care where it appears with major frequency, due to those patients present the conditions for the establishment of fungal infections. The goal of this study was to identify and to know the sensibility of Candida predominant species in the Department of Neonatology of the Maternity “Concepción Palacios”. Of 349 hemocultivos positivos received from january 01 to june 30, 2006; 74 (21.3%) desarrollaron Candida not albicans, with predominance Candida pelliculosa an emergent yeast involved as causal agent of fungemias, that there presented a pattern of changeable sensibility.