Is Candida auris here to stay? An interview with Dimitrios Kontoyiannis.

In this exclusive interview, Dimitrios P Kontoyiannis discusses current mycology hot topic, Candida auris. With a focus on the current knowns and unknowns for the pathogenesis, resistance and transmission of this emerging fungal pathogen, in addition to a look at therapeutics and future perspectives. This interview was conducted by Ellen Colvin, Commissioning Editor of Future Microbiology. Dimitrios P Kontoyiannis is the Texas 4000 distinguished endowed professor and deputy head in the Division of Internal Medicine at MD Anderson Cancer Center in Houston (TX, USA). Dr Kontoyiannis has authored over 550 peer-reviewed manuscripts and has given over 330 lectures in national and international conferences and academic institutions in the USA and abroad. He is considered a leading mycology expert world-wide with an H index of 101 and over 43,000 citations. His research group is credited for many and sustained contributions to clinical, translational and experimental mycology. He is the recipient of many national and international awards and is the past president elect of Immunocompromised Host Society (2016-2018).

Infection control measures to prevent hospital transmission of candida.

Invasive candida infections are the most important causes of nosocomial infections in intensive care units and in risky groups such as immunosuppressed patients. These infections lead to undesirable consequences such as increased morbidity and mortality in patients, prolongation of hospital stay, and increased hospital costs. In recent years, the incidence of non-albicans Candida spp.'s has increased. Unfortunately, some of these species are naturally resistant to first-line antifungals. In addition, biofilm formation on the central venous catheter and invasive devices may cause treatment failure. The age of the patients, co-morbid diseases, the units where they are treated, the antibiotics and antifungals that are used for the treatment, and invasive devices are risk factors for invasive candida infections. Some of these risk factors can be reduced by the behavior of health-care workers. The most important goal is to take precautions before the occurrence of invasive candida infections. Infection control measures to prevent hospital transmission of candida are very important. Compliance with hand hygiene before and after contact with the patient is the most important step to prevent the spreading of Candida spp. Observation of maximal barrier precautions during invasive catheterization is another important clause of this aim. Avoiding unnecessary invasive devices, antibiotics, and parenteral nutrition are also important to reduce the colonization of candida.

[Spectrum of pathogens in postoperative complications of visceral surgery : The problem of multidrug resistance]. / Erregerspektrum postoperativer Komplikationen in der Viszeralchirurgie : Das Problem der Multiresistenz.

In general surgery the etiology of surgical site infections has not significantly changed over the last 30 years. Gram-positive bacteria, e.g. coagulase negative staphylococci (CNS), Staphylococcus aureus and Enterococcus spp. as well as Gram-negative bacteria, e.g. Escherichia coli, Enterobacter spp., Klebsiella spp. and Pseudomonas aeruginosa, are the most common findings. Although in general surgery 10% of the S. aureus causing postoperative wound infections were methicillin resistant (MRSA), no cases of multidrug-resistant Gram-negative (MRGN) bacteria were reported. Yeasts (particularly Candida spp.) are rarely the pathogen causing surgical site infections (≤3%) and concomitant risk factors are typical (e.g. diabetes, chemotherapy, immunosuppression and malnutrition). Viruses are rarely the cause of surgical site infections. Transmission can occur by HBV, HCV or HIV positive surgical staff or in organ transplantations and postoperative reactivation of persistent infections is possible (especially for HBV, HCV, CMV, EBV and HIV). The principles for prevention of surgical site infections are dealt with as consequences of preoperative colonization by MRSA, methicillin-sensitive S. aureus (MSSA) and MRGN and reviewed with respect to screening, perioperative antibiotic prophylaxis and decolonization. In nosocomial peritonitis, the selection of antibiotics should consider previous antibiotic treatment. A single intra-abdominal detection of Candida spp. usually does not require antimycotic treatment in postoperatively stable and immunocompetent patients but is recommended in severe community-acquired or nosocomial peritonitis. Viral infections can be avoided by screening of organ donors and serological surveillance of surgery personnel.

Candida Interface Infections After Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To describe 2 Candida interface keratitis infections occurring in the setting of positive donor rim cultures from precut corneal tissue used for Descemet stripping automated endothelial keratoplasty (DSAEK) and the ensuing public health investigation. METHODS: Following 2 clinical Candida interface keratitis infections, patients from 2012 to 2014 in the same surgical center were evaluated for bacterial and fungal rim cultures and subsequent infection. All cases of fungal infections occurring post-DSAEK were analyzed. Data included patient demographics, surgical technique, donor rim cultures, donor mate outcomes, clinical courses, and outcomes. A review of the relevant literature was also undertaken. RESULTS: From 2012 to 2014, among 99 DSAEK procedures performed, 7 (7.1%) donor rim cultures were positive for fungi. Use of this tissue with positive donor rim cultures resulted in 2 (28.6%) episodes of confirmed fungal interface keratitis, both Candida species, and presumptive treatment in an additional 2 patients. An investigation did not identify any breach in sterile technique or procedures by the surgeon or surgery center. Our literature review identified 15 reports of postoperative fungal infection associated with DSAEK, of which 11 involved Candida spp. CONCLUSIONS: While postoperative infection remains rare, our 2 additional cases along with those previously reported suggest that DSAEK may be susceptible to infection with Candida spp. Furthermore, this report of correlated rim cultures and clinical infection suggests a need for reevaluation of the utility of obtaining routine corneoscleral donor rim fungal culture.

Prevalence and immediate outcome of candida colonized preterm neonates admitted to Special Care Unit of Mulago Hospital, Kampala Uganda.

BACKGROUND: Candida species is the third commonest cause of sepsis among neonates. Colonization by Candida is a predictor for candidemia among preterm neonates. OBJECTIVES: To determine prevalence of early Candida colonization and early outcome among colonized preterm neonates admitted to Mulago hospital Special Care Unit. METHODS: A prospective observational cohort was conducted between December 2008 and April 2009. Preterm neonates aged >72 hours and less than one week were screened for Candida colonization of the groin, oral pharynx and rectum using CHROMagar. Colonized neonates were followed up for 14 days. Blood cultures were done for those with signs of septicaemia. The Fisher's exact tests and logistic regression were conducted for factors associated with colonization and mortality among colonized neonates. P values of < 0.05 were considered significant and confidence interval of 95% was used. RESULTS: Candida colonization occurred in 50/213 (23.5%) neonates. Gestational age ≤ 30 weeks was the only factor independently associated with colonization (p = 0.005). Of the colonized 14/46 (30.4%) died and 13/46 (28.3%) developed mucocutaneous candidiasis. No candidemia was identified. Multiple site colonization was independently associated with mortality (p=0.035). CONCLUSION: The consequence of high colonization observed in this study needs to be further elucidated in Uganda.

Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later.

INTRODUCTION: For decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors. METHODS: We review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection. RESULTS: The recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis. CONCLUSIONS: Despite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.

The transmission of nosocomial pathogens in an intensive care unit: a space-time clustering and structural equation modelling approach.

We investigated the incidence of cases of nosocomial pathogens and risk factors in an intensive treatment unit ward to determine if the number of cases is dependent on location of patients and the colonization/infection history of the ward. A clustering approach method was developed to investigate the patterns of spread of cases through time for five microorganisms [methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter spp., Klebsiella spp., Candida spp., and Pseudomonas aeruginosa] using hospital microbiological monitoring data and ward records of patient-bed use. Cases of colonization/infection by MRSA, Candida and Pseudomonas were clustered in beds and through time while cases of Klebsiella and Acinetobacter were not. We used structural equation modelling to analyse interacting risk factors and the potential pathways of transmission in the ward. Prior nurse contact with colonized/infected patients, mediated by the number of patient-bed movements, were important predictors for all cases, except for those of Pseudomonas. General health and invasive surgery were significant predictors of cases of Candida and Klebsiella. We suggest that isolation and bed movement as a strategy to manage MRSA infections is likely to impact upon the incidence of cases of other opportunist pathogens.

Donor-related Candida keratitis after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report 2 cases of donor-to-host transmission of Candida albicans interface keratitis after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: We performed clinical and microbiologic examinations on 2 patients who underwent DSAEK for pseudophakic corneal edema. RESULTS: Two patients underwent uneventful DSAEK surgery using corneal tissue from the same donor. The donor corneoscleral rims were cultured at the time of surgery and both rims subsequently grew C. albicans and Candida glabrata. Approximately 5 weeks after surgery, infiltrates were noted in the DSAEK interface in both of these patients. Despite treatment with antifungal therapy, the Candida keratitis was unable to be controlled medically and required surgical intervention in each case, after which there was no recurrence of infection. CONCLUSIONS: Candida interface keratitis can occur after DSAEK. These 2 cases emphasize the importance of donor corneoscleral rim cultures, especially with the increase in lamellar and endothelial keratoplasty, which can make such interface infections more difficult to diagnose and treat. Patients with fungal positive donor corneal rim cultures should be prophylactically treated with antifungal therapy.

Surveillance of nosocomial infections: a preliminary study on yeast carriage on hands of healthcare workers.

Hospital-acquired fungal infection is increasing. The aim of this preliminary study was to evaluate the frequency and distribution of yeast carriage on the hands of healthcare workers (HCW) from different departments. The study was conducted in three departments (Surgery, Intensive Care Unit, Obstetrics and Gynaecology) of a hospital in Campania, southern Italy. Over a six-month period, 50 healthcare workers were randomly tested. Imprints of palms and fingertips were taken monthly during the morning shift. The plate with yeast was counted and Candida species were identified. Risk factors for hand contamination were determined. Hand carriage of yeast and Candida species in the three departments were found in the following percentages: Surgery (50% and 49%); Intensive Care Unit (61% and 57%); Obstetrics and Gynaecology (65% and 59%). No significant difference in the frequency or distribution of yeast and Candida sp. recovered in the three departments was ascertained by comparing every two months' data, the hand carriage of yeast and Candida species found in the three departments; this varied - min to max - according to the following percentages: Surgery [(45%-54%) and (42%-58%)]; Intensive Care Unit [(53%-66%) and (56%-59%)]; Obstetrics and Gynaecology [(62%-69%) and (57%-63%)]. The only factor associated with yeast carriage on the hands of healthcare workers was the absence of gloving during healthcare procedure (p = 0.0192). We conclude that in our study yeast carriage on the HCWs' hands is common in the three departments investigated, but its causes are unclear. Careful use of gloving may reduce pathogenic yeast on hands.

Candidosis en pacientes HIV o con otras inmunodeficiencias secundarias en hospitales de la ciudad de Tucumán (Argentina) / Candidosis in HIV patients or with other secondary immunodeficiencies detected in hospitals of the city of Tucumán (Argentina)

Con el objeto de conocer las especies causantes de candidosis humanas en pacientes HIV positivos o con otras inmunodeficiencias secundarias y la incidencia de especies con capacidad de resistencia a antifúngicos, se estudiaron 76 aislamientos de Candida procedentes de 61 casos de candidosis superficiales y profundas de niños y adultos. Obtenidas desde piel, anexos, mucosas, abscesos, catéteres y secreciones diversas, entre otras. La identificación de las especies fue realizada por estudios de características morfológicas, cromogénicas y bioquímicas (CHROMagar , Candifast, API 20 y API 32). Los resultados revelan predominio de especies noalbicans (52.7 por ciento), obteniéndose las siguientes frecuencias de aislamientos: C.albicans (47,3 por ciento), C. parapsilosis: 15,8 por ciento, C. glabrata: 13,2 por ciento, C. krusei: 11,8 por ciento, C. tropicalis: 10,6 por ciento y C. dubliniensis: 1,3 por ciento. Algunas de ellas pueden presentar resistencia primaria o secundaria a algunos antifúngicos de uso habitual, por lo cual es necesario incluir estudios de sensibilidad a estos, para una mejor conducta terapéutica.

In order to find out species causing human candidosis in positive HIV patients or in individuals suffering from other secondary immunodeficiencies and the incidence of species bearing a resistance ability to antifungal agents, 76 Candida isolations obtained from 61 cases of superficial and deep candidosis in children and adults were studied. Samples were collected from skin, annexa, mucosities, abscesses, catheters and diverse secretions, among others. The identification of species was carried out through studies on morphological, chromogenic and biochemical characteristics (CHROMagar, Candifast, API 20 and API 32). Results reveal a predominance of non-albican species (52,7 percent), and the following frequencies of isolation: C.albicans (47.3 percent), C. parapsilosis: 15.8 percent, C.glabrata: 13.2 percent, C. krusei: 11.8 percent, C. tropicalis: 10.6 percent and C. dubliniensis: 1.3 percent. Some of them may exhibit some primary or secondary resistance to certain antifungal agents of common use, this is why it is necessary to include studies on sensitivity of them so as to attain a better therapeutical behaviour.

Candida albicans interface infection after deep anterior lamellar keratoplasty.

PURPOSE: To report a case of interface infection by Candida albicans after deep anterior lamellar keratoplasty (DALK). METHODS: A 30-year-old man with keratoconus underwent DALK. Four weeks after surgery, the patient developed multiple infiltrates in the graft-host interface with absence of intraocular infection. Donor rim cultures grew C. albicans. Penetrating keratoplasty (PK) was performed because of worsening of the infection despite topical, local, and systemic antifungal therapy. RESULTS: Cultures carried out on the excised donor cornea confirmed donor-to-host transmission of C. albicans. An aqueous tap taken before PK was negative. Six months after PK, the corneal graft was clear with no recurrence of infection. CONCLUSIONS: After DALK, in cases of donor graft microbial contamination, infection may develop at the graft-host interface. This may delay or prevent direct intraocular penetration of microorganisms, reducing the risk of development of endophthalmitis. PK may be needed to eradicate the infection in cases where conservative treatment fails.

Multilocus sequence typing reveals intrafamilial transmission and microevolutions of Candida albicans isolates from the human digestive tract.

Candida albicans is a human commensal that is also responsible for superficial and systemic infections. Little is known about the carriage of C. albicans in the digestive tract and the genome dynamics that occur during commensalisms of this diploid species. The aim of this study was to evaluate the prevalence, diversity, and genetic relationships among C. albicans isolates recovered during natural colonization of the digestive tract of humans, with emphasis on Crohn's disease patients who produce anti-yeast antibodies and may have altered Candida sp. carriage. Candida sp. isolates were recovered from 234 subjects within 25 families with multiple cases of Crohn's disease and 10 control families, sampled at the oral and fecal sites. Prevalences of Candida sp. and C. albicans carriage were 53.4% and 46.5%, respectively, indicating frequent commensal carriage. No differences in prevalence of carriage could be observed between Crohn's disease patients and healthy subjects. Multilocus sequence typing (MLST) of C. albicans isolates revealed frequent colonization of a subject or several members of the same family by genetically indistinguishable or genetically close isolates. These latter isolates differed by loss-of-heterozygosity events at one or several of the MLST loci. These loss-of-heterozygosity events could be due to either chromosome loss followed by duplication or large mitotic recombination events between complementary chromosomes. This study was the first to jointly assess commensal carriage of C. albicans, intrafamilial transmission, and microevolution. The high frequency of each of these events suggests that the digestive tract provides an important and natural niche for microevolutions of diploid C. albicans through the loss of heterozygosity.

Canales Endémicos y Marcadores de Resistencia Bacteriana, en Instituciones de Tercer nivel de Bogota, Colombia / Endemic channels and bacterial resistance markers in third-level hospitals in Bogotá, Colombia

Objetivo: Determinar los perfiles de resistencia bacteriana y los canales endémicos en 14 instituciones de tercer nivel. Métodos: Población. Bogotá-Colombia, 14 hospitales pertenecientes al Grupo para el Control de la Resistencia Bacteriana de Bogotá (GREBO). A partir de la información obtenida de los laboratorios de microbiología de los centros participantes (métodos automatizados y manuales), se creó una base de datos usando los programas BacLink 2.0 y Whonet 5.3, durante los años 2001, 2002 y 2003. Los perfiles de susceptibilidad fueron hallados acordes a las normas de la nCCLS (2003). Se realizó un análisis descriptivo de los diferentes marcadores de resistencia y se determinó el canal endémico de la resistencia para los hospitales, utilizando los puntos entre los percentiles 25 y 75 por ciento, para cada mes durante el periodo de estudio. Resultados: Se analizaron 84664 aislamientos. Los más frecuentes fueron Escherichia coli, Staphylococcus aureus, Staphylococcus coagulasa negativo, Klebsiella pneumoniae y Pseudomonas aeruginosa. La resistencia para los años 2001, 2002 y 2003 fue respectivamente: S. aureus meticilino resistente: 41 por ciento, 48 por ciento, 48 por ciento; Staphylococcus coagulasa negativo resistente a oxacilina: 75 por ciento, 73 por ciento, 72 por ciento; E. faecium vancomicina resistente: 14 por ciento, 9 por ciento, 3 por ciento; K. pneumoniae resistente a cefalosporinas de tercera generación: 37 por ciento, 25 por ciento, 23 por ciento; P. aeruginosa resistente a imipenem: 24 por ciento, 22 por ciento, 17 por ciento; P. aeruginosa resistente a ciprofloxacina: 46 por ciento, 46 por ciento, 35 por ciento, A. baumannii resistente a imipenem: 11 por ciento, 29 por ciento, 39 por ciento. Los canales endémicos evidenciaron la problemática de la resistencia bacteriana, esta se centró en la presencia de S. aureus meticilino resistente y en el marcado incremento de la resistencia de A. baumanni a imipenem. Conclusiones: Se destacan los altos porcentajes de resistencia para todos los marcadores de impacto epidemiológico a nivel hospitalario especialmente en Unidades de Cuidado Intensivo.

Four-year persistence of a single Candida albicans genotype causing bloodstream infections in a surgical ward proven by multilocus sequence typing.

The present study represents the first application of multilocus sequence typing to retrospectively investigate a suspected outbreak of Candida albicans bloodstream infection cases that occurred in the same hospital ward between July 1987 and October 1991. Results demonstrated that eight bloodstream infections were caused by the same strain, endemic in the ward, over a 4-year period.

Donor-to-host transmitted Candida endophthalmitis after penetrating keratoplasty.

OBJECTIVE: To report the first case of Candida albicans endophthalmitis following penetrating keratoplasty after warm preservation. DESIGN: Observational case report. METHODS: We reviewed the patient's chart and the available literature on fungal endophthalmitis after keratoplasty. RESULTS: After keratoplasty, a 45-year-old man developed an endophthalmitis on the first postoperative day. The same day, results of the culture of the transportation medium were available and revealed Candida albicans. Despite therapy with topical and subtenon amphotericin B, there was no clinical improvement, and a regraft was performed 4 days after the initial corneal transplant. A best corrected visual acuity of 20/32 was achieved. CONCLUSION: The majority of reported cases of postkeratoplasty candidal endophthalmitis are associated with cold storage preservation and a poor prognosis of the affected eye. We describe a case of postkeratoplasty candidal endophthalmitis after organ-cultured preservation, with a final visual acuity above expectations. In our opinion, early diagnosis based on routine culturing of the transportation medium and early removal of the infected corneal graft when local antifungal therapy failed are important factors contributing to the good clinical outcome.

[Yeast-like fungi--occurrence in animals]. / Grzyby drozdzopodobne--wystepowanie u zwierzat.

The yeast-like fungi are typical opportunistic microorganisms which may be a part of normal commensally ontocenosis. Many species of Candida genus may be also a cause of candidosis in human and animals. Clinical symptoms occurred customly in patient with cellular immunity deficiencies. Horizontal (person-to-person) form of transmission is also possible, including family infection or group infection in animals, mostly in birds. According to actual data, zoonotic status of candidosis is still not fully documented. In animals, candidosis more often occurs as endogenic infection. The separate problem is infection of animals with significance suppressed immune system, e.g. with tumor diseases. In necroscopy investigation very often in these animals disseminated candidosis has been observed. On different way the infections of Candida spp. are manifested in birds, when Candida albicans occurs as marginal population of normal intestinal ontocenosis. During stress the intestinal fungal population is growing up for critical value and typical crop candidosis is developing. In our routine diagnostic work we have isolated Candida strains from nutritional tract in laboratory mice. This yeast were isolated also from the bottom of the boxes and from mice faeces.

[Karyotypic investigation of two cases of invasive candidiasis]. / Invaziv iki kandidoz olgusunun karyotipik olarak incelenmesi.

Investigation of the genetic relationship of the three Candida albicans strains isolated from each of two patients, one with C. albicans meningitis and the other with pancreatic pseudocyst (PP), by PFGE (pulsed-field gel electrophoresis), was aimed in this study. Three strains of C. albicans isolated from bloodstream, abscess and drainage fluid of the patient with PP were found to show the same karyotype, while three strains of C. albicans from cerebrospinal fluid, nasopharyngeal swab culture and stool sample of the patient with meningitis were found closely related. As a conclusion, PFGE enables to give valuable information about the probable source of transmission on individual basis in these two invasive candida infections.

Antifungal resistance: the clinical front.

The emergence of resistance and changes in the spectrum of Candida infections have led to an increased interest in susceptibility testing of antifungal drugs. Such testing may be particularly useful in patients with invasive candidiasis who have been previously treated with azole antifungals, those whose infections are not responding to treatment, and those with infections caused by non-albicans species of Candida. The choice of a specific antifungal depends on the clinical status of the patient, the relative toxicity and efficacy of the drug in the given patient population, the infecting species and antifungal susceptibility of the isolate, and the patient's prior exposure to antifungal agents. Infectious Diseases Society of America recommendations for the initial management of candidemia and acute disseminated candidiasis include an azole, caspofungin, amphotericin B (AmB), or a combination of fluconazole plus AmB. Caspofungin and voriconazole show good activity against most Candida species and may be good alternatives for patients with Candida glabrata and Candida krusei infections and for those with relapsing infections.

[Infections by Candida sp. in intensive care. Survey of French practices]. / Infections à Candida sp en réanimation. Enquête sur les pratiques françaises.

OBJECTIVE: The isolation of Candida sp in nosocomial infections is on the increase and over the past 10 years many guidelines for "good" practices and recommendations have been published on the modalities for the management of systemic candidiasis. The aim of this paper was to assess the habits in the intensive care units in this domain in France. METHOD: A transversal survey on the habits was conducted from March to May 2001, using a questionnaire mailed to 200 intensive care units. RESULTS: One hundred eighty questionnaires (surgical reanimation: 12%, medical: 18%, medico-surgical: 70%) out of 200 (92.5%) were returned. The indirect diagnostic examinations: serology, search for antigenemia and PCR (Polymerase Chain Reaction) were never used in 21, 35 and 65% of cases. The systematic search for colonisation (a mean of 4 areas sampled) was conducted in all the patients by 19% of the investigators, in some patients by 53%, and never by 28%. An antifungal treatment was prescribed: in the presence of a positive haemoculture alone, once out of twice if the sample had been taken from a central catheter and in 2 cases out of 3 when the sample was peripheral. It was prescribed 6 times out of 10 after isolation of Candida sp following surgery or on needle aspiration of an intra-abdominal abscess, varyingly in the case of cadiduria, isolation of a Candida sp in a broncho-pulmonary sample or in abdominal draining and positive culture of a catheter, depending on the intensity of the colonisation, the severity of the clinical picture and the presence of factors of risk for Candida infection. It is still prescribed empirically depending on the same elements and the absence of explanation for worsening. When faced with candidemia in a non-neutropenic patient, a central catheter is not changed in 18% of cases. Depending on the microbiology, fluconazole is prescribed in: the identification of yeast without further precision (78% of cases), Candida sp without further precision (86% of cases), Candida non albicans without further precision (57% of cases), C. albicans (93% of cases), Candida non albicans other than C. krusei and C. glabrata (62% of cases), C. glabrata (36% of cases) with an increase in dose in 1 out of 2 cases. In the presence of C. glabrata or C. krusei, amphotericin B is the choice in respectively 51 and 75% of cases. To adapt the treatment.