Invasive Candida Research Articles

MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by Invasive Candida Infection.

Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans). Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format) was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions following invasive Candidal infection. These findings contribute to our understanding of host cell response to Candidal systemic infections.

Amphotericin B bladder irrigation for the treatment of neonatal bladder fungus ball

An 801 gram very premature infant was delivered by Cesarian section at 28 weeks gestation and developed invasive Candida parapsilosis infection at 4 weeks of age complicated with obstructive uropathy, bilateral hydronephrosis and bladder fungus ball. The baby was treated with systemic amphotericin B and bladder irrigation with amphotericin B solution. Treatment resulted in complete eradication of the bladder fungus ball and resolution of the obstructive uropathy. The difficulty of per- forming bladder irrigation in an extremely small premature infant is discussed. This case illustrates the need to investigate for renal involvement in newborns with persistent candidemia and the effectiveness of bladder irrigation with amphotericin B so- lution in the treatment of bladder fungus balls.

Renal Papillary Necrosis Due to Invasive Candida Infection in a Morbidly Obese Patient

Renal Papillary Necrosis Due to Invasive Candida Infection in a Morbidly Obese Patient

The preemptive treatment of invasive Candida infection with reference of corrected colonization index in critically ill patients: a multicenter, prospective, randomized controlled clinical study

To evaluate preemptive treatment for invasive Candida infection (ICI) with reference of corrected colonization index (CCI) in critically ill patients with high risk factors of Candida infection, and to collect the epidemiology data of Candida infection. One hundred and ten critically ill patients with acute physiology and chronic health evaluation II (APACHE II) score>10 were selected from intensive care units (ICUs) of 5 grade III class A hospitals in Tianjin from October 1st 2008 to April 30th 2009, and they were randomly divided into two groups: CCI group and control group (55 cases in each group). CCI was monitored in all patients. In control group the responsible intensivists ordered the treatment according to their own experience, and in CCI group, when the patient's CCI> or =0.4 and with evidence of sepsis, the patients were given anti-Candida immediately. When CCI<0.4, anti-Candida treatment was not given. But when the patients' condition became worse or unstable, complementary anti-Candida treatment was given. There were no significant differences in general data, treatment of diseases of the patients, APACHE II scores, incidence of sepsis and length of ICU stay (LOS) between two groups ( all P>0.05 ). There were 50 patients and 48 patients developing sepsis in control group and CCI group, respectively. In CCI group, the time between the onset of sepsis to beginning of anti-Candida treatment was significantly shorter than the control group [(0.94+/-0.67) days vs. (3.75+/-3.62) days, P<0.05]. In the group of CCI> or =0.4 (57 patients) the LOS [(15.34+/-6.63) days] and the incidence of failure in establishing enteral nutrition (64.9%) were significantly higher than that of the group of CCI<0.4 [53 patients, (7.24+/-3.75) days, 43.4%, both P<0.05]. There was no significant difference in APACHE II scores, incidence of mechanical ventilation and blood purification between two groups ( all P>0.05 ). Analysis of 575 strains of Candida colonized in 110 patients, revealed that C. albicans ranked first (59.3%), C. tropicalis ranked second (10.8%), followed by C. glabrata, Cryptococcus and C. krusei. Application of CCI may enhance the accuracy of timely preemptive treatment for ICI, and facilitate the collection of epidemiological data of Candida in critically ill patients.

Relevance of Candida and other mycoses for morbidity and mortality in severe sepsis and septic shock due to peritonitis

This single-centre retrospective cohort study evaluated the incidence and outcome of mycoses in critical ill patients (n = 283) with sepsis due to peritonitis. Overall mortality was 41.3%, and the 28-day mortality was 29.3%. Fungal pathogens were found in 51.9%. The common first location was the respiratory tract (66.6%), followed by the abdominal site (19.7%). Candida colonisation was found in 64.6%, and invasive Candida infection in 34.0%. Identified fungi were Candida spp. in 98.6% and Aspergillus spp. in 6.1%. Patients with fungal pathogens showed a higher rate of postoperative peritonitis, APACHE II and tracheotomy. In comparison to patients without fungal pathogens, these patients showed a longer duration on mechanical ventilation, and a higher overall mortality. Patients with Candida-positive swabs from abdominal sites had more fascia dehiscence and anastomosis leakage. Seventy-two patients (48.9%) received antifungal therapy, 26 patients were treated empirically. Antifungal therapy was not associated with a decrease in mortality. Age and renal replacement therapy were associated with mortality. In conclusion, fungi are common pathogens in critically ill patients with peritonitis, and detection of fungi is associated with an increase in overall mortality. Particularly, Candida-positive abdominal swabs are associated with an increase in morbidity. However, we were not able to demonstrate a survival benefit for antifungal therapy in peritonitis patients.

Risk factors for fluconazole-resistant invasive candidiasis in intensive care unit patients: An analysis from the China Survey of Candidiasis study

PurposeTo assess the risk factors for invasive Candida infection (ICI) caused by fluconazole-resistant (Flu-R) Candida species in intensive care unit (ICU) patients. Materials and methodsData from China Survey of Candidiasis study were analyzed. Patients with proven ICI were classified into fluconazole-sensitive (Flu-S) and Flu-R groups. Independent risk factors for Flu-R ICI were identified using a multivariate logistic regression. ResultsForty-one percent of ICI patients were infected with Flu-R Candida. Significantly more patients had Candida colonization, intra-abdominal hypertension, and antifungal therapy at least 7 days before diagnosis; fewer patients had gastrointestinal perforation, systemic inflammatory response syndrome manifestation, and fluoroquinolone exposure in the Flu-R group. Furthermore, hospital or ICU stay before onset of infection was longer in the Flu-R group than in the Flu-S group (hospital or ICU stay: 19 vs 13 days or 10.5 vs 8 days, P < .05). Also, it was demonstrated as an independent risk factor for Flu-R Candida infection. ConclusionAs many as 41% of ICI patients were infected with Flu-R Candida, and the main risk factor was longer ICU stay before onset of ICI, implying that caution should be exercised when treating patients who have been long stayed in ICU with fluconazole as the first-line drug before testing isolates for drug sensitivity.

Invasive Candida infections and the harm from antibacterial drugs in critically ill patients: data from a randomized, controlled trial to determine the role of ciprofloxacin, piperacillin-tazobactam, meropenem, and cefuroxime.

Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection. Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010. Nine multidisciplinary ICUs across Denmark. A total of 1,200 critically ill patients. Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596). Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006). High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.

Activation and alliance of regulatory pathways in C. albicans during mammalian infection.

Gene expression dynamics have provided foundational insight into almost all biological processes. Here, we analyze expression of environmentally responsive genes and transcription factor genes to infer signals and pathways that drive pathogen gene regulation during invasive Candida albicans infection of a mammalian host. Environmentally responsive gene expression shows that there are early and late phases of infection. The early phase includes induction of zinc and iron limitation genes, genes that respond to transcription factor Rim101, and genes characteristic of invasive hyphal cells. The late phase includes responses related to phagocytosis by macrophages. Transcription factor gene expression also reflects early and late phases. Transcription factor genes that are required for virulence or proliferation in vivo are enriched among highly expressed transcription factor genes. Mutants defective in six transcription factor genes, three previously studied in detail (Rim101, Efg1, Zap1) and three less extensively studied (Rob1, Rpn4, Sut1), are profiled during infection. Most of these mutants have distinct gene expression profiles during infection as compared to in vitro growth. Infection profiles suggest that Sut1 acts in the same pathway as Zap1, and we verify that functional relationship with the finding that overexpression of either ZAP1 or the Zap1-dependent zinc transporter gene ZRT2 restores pathogenicity to a sut1 mutant. Perturbation with the cell wall inhibitor caspofungin also has distinct gene expression impact in vivo and in vitro. Unexpectedly, caspofungin induces many of the same genes that are repressed early during infection, a phenomenon that we suggest may contribute to drug efficacy. The pathogen response circuitry is tailored uniquely during infection, with many relevant regulatory relationships that are not evident during growth in vitro. Our findings support the principle that virulence is a property that is manifested only in the distinct environment in which host–pathogen interaction occurs.

Candida Glabrata and Candida Tropicalis in an Immunocompetent Patient

Objective: To report a case of Candida glabrata and tropicalis pneumonia in an immunocompetent patient. Case Summary: A 72-year-old male was transferred from an outside institution due to worsening respiratory status, acute kidney injury secondary to intravenous contrast media, sepsis, and pneumonia with fever and leukocytosis. Upon admission, he was initiated on treatment for hospital-acquired pneumonia, but was also concomitantly tested for many other opportunistic infections due to his recent month-long trip to Ecuador where he participated in a tribal treatment for neuropathy that involved direct exposure to dead guinea pigs. With completion of cultures and bronchoalveolar lavage, C. glabrata was identified in the blood culture and C. glabrata and C. tropicalis in the bronchoalveolar lavage specimen. One month later, he was admitted due to recurrent pneumonia. The patient unfortunately expired during the second admission, due to complications from chronic respiratory pulmonary disease and pneumonia. Discussion: Initially, this patient was treated for hospital-acquired pneumonia, but due to a recent trip to Ecuador, it was soon discovered that this patient had developed an invasive Candida pneumonia. His pulmonary biopsies showed growth of invasive C. glabrata and C. tropicalis, while his blood culture showed C. glabrata. Candida-related lower respiratory tract infections are exceptionally rare in immunocompetent patients and require histopathologic evidence to confirm the diagnosis. A second blood culture showed that the C. glabrata was still present and the patient had worsening leukocytosis, so micafungin was added to his antimicrobial therapy. Conclusion: It is understood that pneumonia is rarely caused by Candida species in patients who are admitted to the hospital. However, health care professionals should be aware that Candida pneumonia should be suspected as part of the differential diagnosis even in immunocompetent patients, particularly if they have recently traveled outside the United States.

T2 Magnetic Resonance Assay for the Rapid Diagnosis of Candidemia in Whole Blood: A Clinical Trial

Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species. T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. NCT01752166.

Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis.

The aim of this study was to investigate the role of cytokine genes in the susceptibility to Candida infection. A total of 275 consecutive patients diagnosed with Candida infection were selected between May 2010 and May 2011, along with 305 uninfected controls. Genotyping of the IL-1β gene polymorphisms (IL1β) rs1143634, IL1βrs16944, IL8 rs4073, IL10 rs1800872, and IL10 rs1800896 was carried out using a 384-well plate format on the Sequenom MassARRAY platform. Patients with invasive Candida infections were more likely to have had an immunocompromised state, hematopoietic stem cell transplantation, solid organ transplant, solid tumor, chemotherapy within the past three months, neutropenia, surgery within the past 30 days, acute renal failure, liver failure, and/or median baseline serum creatinine. Conditional logistic regression analyses found that individuals with the rs1800896 GG genotype were associated with a higher risk of invasive Candida infections than those carrying the AA genotype (odds ratio = 0.61, 95% confidence interval = 0.37-0.94). From the results of this case-control study, we suggest that the cytokine IL-10 gene rs1800896 polymorphism might play a role in the etiology of invasive Candida infections.

Preventing invasive candida infections. Where could we do better?

Invasive candidiasis is associated with high mortality rates, ranging from 35% to 60%, in the range reported for septic shock. The epidemiology and pathogenesis of invasive candidiasis differ according to the patient's immune status; the majority of cases in immunocompromised hosts are candidaemia, whereas non-candidaemic systemic candidiasis accounts for the majority of cases in critically ill patients. In contrast to candidaemia, non-candidaemic systemic candidiasis is difficult to prove, especially in critically ill patients. Up to 80% of these patients are colonized, but only 5-30% develop invasive infection. The differentiation of colonization and proven infection is challenging, and evolution from the former to the latter requires seven to 10 days. This continuum from colonization of mucosal surfaces to local invasion and then invasive infection makes it difficult to identify those critically ill patients likely to benefit most from antifungal prophylaxis or early empirical antifungal treatment. Early empirical treatment of non-candidaemic systemic candidiasis currently relies on the positive predictive value of risk assessment strategies, such as the colonization index, candida score, and predictive rules based on combinations of risk factors such as candida colonization, broad-spectrum antibiotics, and abdominal surgery. Although guidelines recently scored these strategies as being supported by limited evidence, they are widely used at bedside and have substantially decreased the incidence of invasive candidiasis.

Invasive Candida Infections in Pediatric Patients Treated on the Pilot Study of Decitabine and Vorinostat with Chemotherapy for Relapsed ALL: A Report from the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Consortium

▪Introduction Children and young adults with relapsed acute lymphoblastic leukemia (ALL) are at high risk for infectious complications, particularly invasive fungal infections, during their intensive re-induction therapy. We report results of a Pilot study investigating decitabine and vorinostat in combination with intensive re-induction chemotherapy for children and young adults with relapsed or refractory ALL. This study is currently open through the TACL Consortium [NCT01483690] and all patients and/or their parents or guardians signed informed consent to participate in this institutional review board approved therapeutic trial in accordance to the Declaration of Helsinki.Methods Patients 1-25 years of age with 2nd or greater relapse or refractory ALL are eligible. Seventeen patients have enrolled with a median age of 12 years (range, 19 months - 21 years). Patients received one course of therapy which included decitabine (15mg/m2 days 1-7; 15-21), vorinostat (180mg/m2 days 3-10; 17-24), vincristine (1.5mg/m2 days 10, 17, 24, 31), dexamethasone (10mg/m2/dose BID days 8-12; 22-26), mitoxantrone (10mg/m2 days 8, 9), PEG-asparaginase (2500 IU/m2 days 10, 24) and intrathecal methotrexate (dosed according to age and CNS status). Nine patients (53%) relapsed after a prior allogeneic hematopoietic cell transplant and 5 patients had refractory disease (29%) prior to enrolling on this study. Initial infection prophylaxis guidelines did not require anti-bacterial or anti-fungal therapy.Results The study was suspended after 5 patients enrolled due to 2 patients reporting a DLT [Grade 3 cholestasis/steatosis, Grade 4 bilirubin (n=1); Grade 3 delirium, Grade 4 seizure, Grade 4 somnolence (n=1)] and 4 of the 5 patients (80%) reporting non-albicans Candidemia [C. kruseii (n=2), C. lusitaniae (n=1), C. guillermondii (n=1)]. Based on this significant rate of fungal infection, despite all patients receiving prophylactic anti-fungal therapy (micafungin n=2, fluconazole n=1, amphotericin n=1), the study was amended to decrease the decitabine dose (15mg/m2 to 10mg/m2) and duration of decitabine (days 1-7; 15-21 to 1-5; 15-19) as well as require treatment dose non-azole class anti-fungal therapy (echinocandin or amphotericin) to be given to all patients on study. Twelve patients enrolled post-amendment; only 1 of 12 (8.3%) experienced a fungal infection (C. guillermondii). Of note, this infection occurred in a patient using fluconazole for prophylaxis in place of a protocol-specified agent. There have been no fungal infections reported to date for the 11 patients on study who have received echinocandin or amphotericin therapy at treatment doses. Treatment responses include 9 patients achieving a complete remission (CR) (53%), 5 with stable disease (29%), two treatment related deaths and 1 patient removed from protocol therapy on day 6 based on the physician’s decision. The median minimal residual disease (MRD) response in patients who achieved a CR and submitted bone marrow samples for end of therapy testing (n=5) was 0.056% (range, 0.00%-5%).Conclusions We report a substantial initial incidence of invasive Candida infections in patients treated with decitabine and vorinostat in combination with intensive chemotherapy despite anti-fungal prophylaxis which appears to be abrogated once the fungal prophylaxis was required at treatment doses using either an echinocandin or amphotericin class agent. As well, the lower dose and duration of decitabine may have contributed to this improvement, resulting in potentially shorter periods of neutropenia which may contribute to the risk of fungal disease. The mechanism for the unique propensity for non-albicans Candida infections in this study remains unclear. The initial response to this regimen incorporating epigenetic therapy is promising with correlative biology studies investigating methylation, acetylation and gene expression changes pending study completion. The study continues to accrue at a dose expansion cohort. DisclosuresOff Label Use: Decitabine in relapse ALL Vorinostat in relapse ALL.

New synthetic sulfone derivatives inhibit growth, adhesion and the leucine arylamidase APE2 gene expression of Candida albicans in vitro

The successful preventing and effective treatment of invasive Candida albicans infections required research focused on synthesis of new classes of agents and antifungal activity studies. Bromodichloromethyl-4-chloro-3-nitrophenyl sulfone (named compound 6); dichloromethyl-4-chloro-3-nitrophenyl sulfone (named 7); and chlorodibromomethyl-4-hydrazino-3-nitrophenyl sulfone (named 11) on inhibition of planktonic cells’ growth, leucine arylamidase APE2 gene expression, and adhesion to epithelial cells were investigated. In vitro anti-Candida activities were determined against wild-types, and the morphogenesis mutants: Δefg1 and Δcph1. MICs of compounds 6, 7 and 11 (concentrated at 0.25–16μg/ml) were determined using the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document). APE2 expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells growth in YEPD and on Caco-2 cell line. Adherence assay of C. albicans to Caco-2 was performed in 24-well-plate.The structure activity relationship suggested that sulfone containing hydrazine function at C-1 (compound 11) showed higher antifungal activity (cell inhibition%=100 at 1–16μg/ml) than the remaining sulfones with chlorine at C-1. Δcph1/Δefg1 was highly sensitive to compound 11, while the sensitivity was reduced in Δcph1/Δefg1::EFG1 (%=100 at 16-fold higher concentration). Compound 11 significantly affected adherence to epithelium (P ⩽0.05) and hyphae formation. The APE2 up-regulation plays role in sulfones’ resistance on MAP kinase pathway. Either CPH1 or EFG1 play a role in the resistance mechanism in sulfones. The strain-dependent phenomenon is a factor in the sulfone resistance mechanism. Sulfones’ mode of action was attributed to reduced virulence arsenal in terms of adhesiveness and pathogenic potential related to the APE2 expression and morphogenesis.

Editorial introductions

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Monica A. SlavinMonica A. SlavinMonica A. Slavin MBBS, FRACP, MD, is based in Melbourne, Australia, where she has been Head of the Department of Infectious Diseases at the Peter MacCallum Cancer Centre since 2000 and Head of the Immunocompromised Host Infection Service at Royal Melbourne Hospital, Australia, since 2013. She is a Professor in the Department of Medicine at the University of Melbourne, Australia and a Research Associate at the Macfarlane Burnet Centre for Medical Research and Public Health. Professor Slavin received her medical degree from the University of Melbourne and trained in Infectious Diseases in both Melbourne and in the Infectious Diseases Program at the Fred Hutchison Cancer Research Center in Seattle, USA. She has been an infectious diseases physician since 1993 with a major interest in infections in immunocompromised patients, especially those with cancer and undergoing stem cell transplantation. Her current research focus is prevention diagnosis and early treatment of invasive fungal infections in haematology patients. She has served on national steering committees for the development of antifungal and fever and neutropenia treatment guidelines and for the conduct of Australia-wide studies of the epidemiology of fungal infection. She is chair of the Australian & New Zealand Mycoses Interest Group, leads the writing group for the Australasian Society for Infectious Diseases (ASID) guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections. She is vice-president of the International Immunocompromised Host Society. William IrvingWilliam IrvingProfessor Irving has been Professor and Honorary Consultant in Virology at the University of Nottingham, UK, and Nottingham University Hospitals NHS Trust, UK, since 2002, having previously been Senior Lecturer (1990–1996) and Reader (1997–2001). His particular interest is in the field of viral hepatitis and he has been a member of the Department of Health Advisory Group on Hepatitis (AGH) since 1998, becoming Chair in 2009. Professor Irving is co-chair for HCV Research UK, a multicenter, multidisciplinary effort to create a national cohort of 10,000 patients with HCV infection, together with a clinical database and biobank, to act as a resource for future research. His recent publications include: Lattimore S, Irving W, Collins S, Penman C, Ramsay M; On behalf of the collaboration for the sentinel surveillance of blood-borne virus testing. Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection. Hepatology. 2014; 59: 1343-50. Irving W, Rupp D, McClure CP, Than LM, Titman A, Ball JK, Steinmann E, Bartenschlager R, Pietschmann T. Development of a high-throughput pyrosequencing assay for investigation of temporal evolution and levels of resistance archiving in the Hepatitis C virus protease gene. Antiviral Research 2014; 110C: 52-59.

Invasive Candida infections in patients of a medical intensive care unit: attempt of improving diagnosis by quantifying the colonization.

During the past decades, a steady increase in the incidence of invasive Candida infections in patients requiring intensive care has been reported. Nevertheless, the diagnosis of invasive Candida infections in the intensive care unit setting remains still difficult and is often made late in the course of disease. Additionally, prognosis worsens rapidly with delayed initiation of antifungal therapy. Clinical scoring systems such as the Candida colonization index or the four risk factor-based Candida score could be very useful tools to select patients at high risk of developing invasive Candida infections, who would benefit from the administration of systemic antifungal therapy. The main objective was to determine the incidence of invasive Candida infection among patients of a medical intensive care unit and to investigate its association with the Candida colonization index and the Candida score. A prospective, observational, single-center study was performed from December 2010 to December 2011. All patients over the age of 18 years who were admitted for at least 7 days in a medical intensive care unit were included. Demographic characteristics, underlying diseases, reasons for intensive care unit admission and presence and duration of risk factors for Candida species colonization and infection were collected for each patient. The Candida colonization index and the Candida score were calculated weekly until discharge or death. A total of 65 patients were included. Proven invasive Candida infections were diagnosed in five patients (7.7 %), i.e. two developed candidemia, two peritonitis, and one pneumonia. All of these patients were characterized by a Candida colonization index ≥ 0.5 (incidence rate: 16.7 % [5/30]) and a Candida score ≥ 2.5 (incidence rate: 29.4 % [5/17]). Mechanical ventilation (p = 0.013) and both Candida scoring systems (p = 0.013 versus p < 0.001) were statistically and significantly associated with invasive Candida infections. The mortality rate was high (80 %). Interestingly, treatment with antifungal drugs was not statistically and significantly associated with invasive candidiasis (p = 0.077) and patients outcome (p = 0.057). Both the Candida colonization index and the Candida score with cut-off values ≥ 0.5 and ≥ 2.5 are very useful tools to select patients at high risk of developing invasive Candida infections in the medical intensive care unit setting, who would benefit from early antifungal treatment.

Invasive Candida infections in surgical patients in intensive care units: a prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006–2008)

A prospective, observational, multicentre study of invasive candidosis (IC) in surgical patients in intensive care units (ICUs) was conducted from 2006 to 2008 in 72 ICUs in 14 European countries. A total of 779 patients (62.5% males, median age 63 years) with IC were included. The median rate of candidaemia was 9 per 1000 admissions. In 10.8% the infection was already present at the time of admission to ICU. Candida albicans accounted for 54% of the isolates, followed by Candida parapsilosis 18.5%, Candida glabrata 13.8%, Candida tropicalis 6%, Candida krusei 2.5%, and other species 5.3%. Infections due to C. krusei (57.9%) and C. glabrata (43.6%) had the highest crude mortality rate. The most common preceding surgery was abdominal (51.5%), followed by thoracic (20%) and neurosurgery (8.2%). Candida glabrata was more often isolated after abdominal surgery in patients ≥60 years, and C. parapsilosis was more often isolated in neurosurgery and multiple trauma patients as well as children ≤1 year of age. The most common first-line treatment was fluconazole (60%), followed by caspofungin (18.7%), liposomal amphotericin B (13%), voriconazole (4.8%) and other drugs (3.5%). Mortality in surgical patients with IC in ICU was 38.8%. Multivariate analysis showed that factors independently associated with mortality were: patient age ≥60 years (hazard ratio (HR) 1.9, p 0.001), central venous catheter (HR 1.8, p 0.05), corticosteroids (HR 1.5, p 0.03), not receiving systemic antifungal treatment for IC (HR 2.8, p <0.0001), and not removing intravascular lines (HR 1.6, p 0.02).

Preliminary evidence for a serum disaccharide signature of invasive Candida albicans infection detected by MALDI Mass Spectrometry

The diagnosis of systemic Candida infections is a recognized challenge. We developed a mass spectrometry strategy to detect signals from Candida molecules in patients’ sera. Pre-analytical procedures were designed to extract oligosaccharides from serum. A peak m/z of at 365 was specifically revealed in sera from patients with candidaemia with regard to healthy controls. This biomarker was identified as a disaccharide, its presence did not correlate with mannanaemia or glucanaemia. Mouse models of Candida albicans colonization and infection showed that the signal was specifically associated with tissue invasion, suggesting that clinical evaluation of its usefulness in discriminating colonized and infected patients would be worthwhile.

Host genetics of invasive Aspergillus and Candida infections.

Invasive candidiasis and aspergillosis are major complications in surgical and onco-hematological patients, and still associated with an important morbidity and mortality. A large number of studies highlighted the potential role of host genetic polymorphisms that may influence susceptibility to fungal pathogens, but many were limited by insufficient statistical power, problematic design, and/or lack of replication. However, some relevant polymorphisms are now emerging from well-conducted studies whose associations have been replicated and/or are supported by strong biological evidence. Such polymorphisms together with other biomarkers may play a role in the prediction, diagnosis, and management of severe fungal infections in high-risk patients in the coming years.

PO-0524 Neonatal Systemic Candidiasis: A 12-year Study

Background Invasive Candida species have become a common cause of late-onset sepsis in neonatal intensive care units. Significant risk factors include low birth weight, exposure to broad spectrum antibiotics, parenteral nutrition, lipid emulsion, central venous catheter and abdominal surgery. Material and method We performed a retrospective study over a period of 12 years (Jan 2002 to Jan 2014) in our hospital NICU. The aims of this study were to investigate the incidence of the systemic candidiasis, mortality rate, the implicated Candida strains, specific risk factors and antifungal treatment. Results All of our cases were outpatients. The average incidence of systemic candidiasis was 5.8% (111 cases) with a specific average mortality of 28%. In 96 cases (86.5%) not albicans Candida species were identified. 83 patients (74.7%) underwent abdominal surgery interventions; from these 42 had malformations of digestive tract and 16 presented abdominal wall defects. 12 operated patients remained with temporary ileostomies, 5 had colostomies and 4 cases associated short bowel syndrome. Also 23 (20.7%) were premature with birth weight under 1500 g; 25 cases presented also a bacterial sepsis. The antifungal therapy consisted of Fluconazol iv during the period 2002–2006; starting 2007 we used mainly Caspofungin iv. Also, starting 2011 all the patients with risk factors received oral prophylaxis with Nistatin. Conclusions Neonatal sepsis with Candida species still has a high rate of mortality and morbidity mainly linked of specific risk factors and other severe illnesses. Thereof more randomised trials regarding both oral and iv prophylaxis are needed.