Risk Factors For Invasive Candidiasis Research Articles

Risk Factors for Invasive Candidiasis in Critically Ill Patients Who Underwent Emergency Gastrointestinal Surgery for Complicated Intra-Abdominal Infection.

Background: Candida species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to evaluate invasive candidiasis (IC) risk factors in critically ill patients undergoing surgery. Patients and Methods: We retrospectively reviewed the medical records of 583 patients who underwent emergency surgery for complicated intra-abdominal infections between January 2016 and December 2021. Patients were divided into two groups according to the presence or absence of IC during their hospital stay. IC was defined as culture-proven candidemia and intra-abdominal candidiasis. Results: This study included 373 patients for the final analysis, of whom 320 were discharged without IC (IC absent group) and 53 presented with IC (IC present group) during their hospital stay. The IC present group showed a higher in-hospital mortality rate (35.8 vs. 8.8%; p < 0.001), with 66.0% of the patients diagnosed within 10 days, whereas only 6.5% were diagnosed beyond 20 days after admission. Stomach (odds ratio [OR], 4.188; 95% confidence interval [CI], 1.204-14.561; p = 0.024) and duodenum (OR, 7.595; 95% CI, 1.934-29.832; p = 0.004) as infection origin, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR, 1.097; 95% CI, 1.044-1.152; p < 0.001), and lower initial systolic blood pressure (OR, 0.983; 95% CI, 0.968-0.997; p = 0.018) were risk factors of IC after emergency gastrointestinal surgery. Conclusions: Patients who had stomach and duodenum as infection origin, higher APACHE II scores, and lower initial systolic blood pressure had a higher risk of developing IC during their hospital stay after emergency gastrointestinal surgery. Prophylactic antifungal agents can be carefully considered for critically ill patients with these features.

Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis.

Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

Distribution of candida species and risk factors for invasive candidiasis

Aim: The aim of this study was to investigate the Candida species isolated from the clinical samples of patients in the pediatric intensive care unit and to determine the risk factors for invasive candidiasis. Materials and Methods: Patients with Candida species detected in clinical samples between January 2013 and December 2018 were included in this study. The demographic characteristics of the patients, the use of broad-spectrum antibiotics and immunosuppressive drugs, underlying diseases, blood transfusions, history of surgical operations, whether there is bacterial growth with Candida species in the same clinical sample, parenteral nutrition and invasive interventions were retrospectively analyzed and their relationship with invasive candidiasis was investigated. Results: A total of 91 patients were included in the study. The mean age was 72.3 ± 70.1 months. Among the patients 48.4% had Candida albicans while 51.6% had non-albicans Candida. Candida parapsilosis (n = 18, 19.8%) and Candida tropicalis (n = 14, 15.4%) were the most common non-albicans Candida species. The most common antifungal treatment was fluconazole (n = 34, 59.6%). There was no statistically significant relationship between invasive candidiasis and the underlying disease, central venous and / or urinary catheter, broad-spectrum antibiotic, corticosteroid, gender and surgical operation (p&amp;gt; 0.05). On the other hand, there was a statistically significant relationship between invasive candidiasis and parenteral nutrition, blood transfusion and bacterial growth with Candida species in the same clinical sample (p &amp;lt;0.05). Conclusions: Non-albicans Candida species are more common than Candida albicans in the pediatric intensive care units. Candida parapsilosis is the most common among non-albicans Candida species. Parenteral nutrition, blood transfusion and bacterial growth with Candida species in the same clinical sample increased the risk of invasive candidiasis.

Effect of empirical antifungal treatment on mortality in non-neutropenic critically ill patients: a propensity-matched retrospective cohort study.

To evaluate the effect of empirical antifungal treatment (EAFT) on mortality in critically ill patients without invasive fungal infections (IFIs). This was a single-center propensity score-matched retrospective cohort study involving non-transplanted, non-neutropenic critically ill patients with risk factors for invasive candidiasis (IC) in the absence of IFIs. We compared all-cause hospital mortality and infection-attributable hospital mortality in patients who was given EAFT for suspected IC as the cohort group and those without any systemic antifungal agents as the control group. Among 640 eligible patients, 177 patients given EAFT and 177 control patients were included in the analyses. As compared with controls, EAFT was not associated with the lower risks of all-cause hospital mortality [odds ratio (OR), 0.911; 95% CI, 0.541-1.531; P = 0.724] or infection-attributable hospital mortality (OR, 1.149; 95% CI, 0.632-2.092; P = 0.648). EAFT showed no benefit of improvement of infection at discharge, duration of mechanical ventilation, and antibiotic-free days. However, the later initiation of EAFT was associated with higher risks of all-cause hospital mortality (OR, 1.039; 95% CI, 1.003 to 1.076; P = 0.034) and infection-attributable hospital mortality (OR, 1.046; 95% CI, 1.009 to 1.085; P = 0.015) in patients with suspected IC. This effect was also found in infection-attributable hospital mortality (OR, 1.042; 95% CI, 1.005 to 1.081; P = 0.027) in septic patients with suspected IC. EAFT failed to decrease hospital mortality in non-neutropenic critically ill patients without IFIs. The timing may be critical for EAFT to improve mortality in these patients with suspected IC. ChiCTR2000038811, registered on Oct 3, 2020.

P004 Neglected risk for of invasive candidiasis: s tudy of distribution, species differentiation and antifungal susceptibility pattern of Candidemia among patients with liver disease

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesPatients with liver disease (LD) are more predisposed to candidemia due to the dysfunctional Kupffer cells which fails to capture the circulating yeasts, thereby causing fungal dissemination. Candidemia is ten times more common among end-stage liver disease patients compared with other LD patients. Compared to those with abdominal candidiasis, ICU admission and mortality are found to be higher in liver transplant recipients (LTRs) with candidemia. Though a majority of Candida infection among LD patients are due to C. albicans, there has been an increasing prevalence of non-albicans isolates. This study was mainly aimed at species differentiation and antifungal susceptibility. Our objective was to study the pattern of Candida isolates from blood among patients with different LD states admitted to tertiary care Liver Hospital. To determine the distribution of Candidemia in patients with different liver disease states. To determine the various species of Candida isolated from blood in patients with liver diseases. To determine the anti-fungal susceptibility pattern of Candida isolates in blood in patients with liver disease. To determine the year-wise changing trends in Candida spp. isolated in blood and its anti-fungal susceptibility pattern in patients with liver disease.Materials and MethodsThis is a retrospective observational study conducted in the department of Microbiology at Institute of Liver and Biliary Sciences (ILBS), New Delhi. Ethical approval for this study (IEC/2021/84/NA06) was provided by the Institutional ethics committee/Institutional review board. A total of 118 LD patients with candidemia who were admitted to ILBS between January 2017 to December 2020 were included in the study. Clinical details of these patients were collected from the hospital information system. Patients with LD were divided into 4 groups—acute liver failure (ALF), acute on chronic liver failure (ACLF), chronic liver disease (CLD), and post-liver transplantation (Post-LT). Candida speciation as identified by VITEK® 2 (Biomérieux) and also its antifungal susceptibility pattern by broth microdilution.ResultsThe mean age of the 118 LD patients was 48.6 ± 14.9 years [± standard deviation (SD)]. Among them 107 (90.7%) were males and 11 (9.3%) were females. Among the 118 LD patients, 6 (5.1%) were ALF patients, 32 (27.1%) were ACLF patients, 66 (55.9%) were CLD patients and 14 (11.9%) were post-LT patients. The most common Candida species isolated was C. tropicalis (22.9%), followed by C. glabrata (17.8%), C. albicans (16.9%), C. parapsilosis (12.7%), C. auris (8.5%), C. krusei (6.8%) and other Candida species (14.4%). The other Candida species isolated were C. haemulonii, C. kefyr, C. lusitaniae, C.pelliculosa, C. duobushaemulonii, C. lipolytica, and C. rugosa. The sensitivity to fluconazole (55.1%), voriconazole (86.4%), caspofungin (82.2%), micafungin (97.5%), flucytosine (80.5%), amphotericin B (86.4%). Mortality was 66%.ConclusionOur study shows that chronic liver disease, acute liver failure and liver transplantation are important risk factors for invasive candidiasis. There was a rise in the non-albicans Candida, especially C. tropicalis and C. glabrata. There is rising antifungal resistance to azoles and can lead to therapy failure. Hence antifungal sensitivity testing is essential in patients with these neglected risk factors to prevent mortality.

Invasive candidiasis among high prevalence neurological patients.

Invasive candidiasis is a severe form of infection. The incidence of invasive fungal infections has increased, due to the increasing number of patients with impaired immunity who are being treated through prolonged stay in hospital facilities. Neurological patient treatment methods such as antimicrobials, corticosteroid, central venous catheter (CVC), total parenteral nutrition, and mechanical ventilation use are associated with common risk factors for invasive candidiasis. Our study demonstrated invasive candidiasis prevalence among neurological patients. A cross-sectional study was done with consecutive sampling of neurological patients who were hospitalized from January 2017 to February 2020 at the Mahar Mardjono National Brain Center Hospital East Jakarta Indonesia. Patients with sepsis, septic shock, or fever (> 38.5 °C), and who had not received antifungals before culture were enrolled in the study. Clinical specimens were obtained from blood, liquor cerebrospinal or other sterile sites, CVC, respiratory tract specimens, and urine or other non-sterile sites. Socio-demographic data, potential risk factors based on previous studies, clinical, and other tests data were obtained from medical records. Classification of invasive candidiasis was according to the Paphitou classification criteria. One hundred and two subjects met the study criteria. The prevalence of invasive candidiasis in neurological patients was 13.7%. All of the isolates were C. parapsilosis. The prevalence of invasive candidiasis was high in the samples studied. The infection was associated with septic shock, tracheostomy, and duration of use of central venous catheter, ventilator, and steroids.

Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria

Antibiotics are a modifiable iatrogenic risk factor for the most common human nosocomial fungal infection, invasive candidiasis, yet the underlying mechanisms remain elusive. We found that antibiotics enhanced the susceptibility to murine invasive candidiasis due to impaired lymphocyte-dependent IL-17A- and GM-CSF-mediated antifungal immunity within the gut. This led to non-inflammatory bacterial escape and systemic bacterial co-infection, which could be ameliorated by IL-17A or GM-CSF immunotherapy. Vancomycin alone similarly enhanced the susceptibility to invasive fungal infection and systemic bacterial co-infection. Mechanistically, vancomycin reduced the frequency of gut Th17 cells associated with impaired proliferation and RORγt expression. Vancomycin's effects on Th17 cells were indirect, manifesting only invivo in the presence of dysbiosis. In humans, antibiotics were associated with an increased risk of invasive candidiasis and death after invasive candidiasis. Our work highlights the importance of antibiotic stewardship in protecting vulnerable patients from life-threatening infections and provides mechanistic insights into a controllable iatrogenic risk factor for invasive candidiasis.

Differences in Levels of Human 1,3β-D-Glucan from Bronchoalveolar Lavage (BAL) Fluid in The Immunocompromised and Immunocompetent Groups Patients with Suspected Lung Cancer

Background: Invasive candidiasis occurs in immunocompromised individuals as an opportunistic infection in patients with lung cancer. Although culture and histopathology remain the standard diagnosis of fungal infections, other tests are still needed to provide faster results. Human 1,3-β-D-Glucan (BDG) uses ELISA to detect candidiasis. β D-Glucan level from BAL fluid is positive when the cut-off is p 130 pg / mL. This study aims to determine differences in the levels of Human 1,3β-D-Glucan from Bronchoalveolar Lavage (BAL) fluid between the immunocompromised and immunocompetent groups in patients with suspected lung cancer at RSU Dr. Saiful Anwar Malang.Method: A cross-sectional study was conducted on 33 lung cancer patients who had risk factors for invasive candidiasis in Dr. Saiful Anwar Hospital Malang.Result: 33 study patients had significant differences in BAL levels of Human 1,3β-D-Glucan in the immunocompromised and immunocompetent groups (p = 0.009). In the different tests, there was a slight difference in the levels of BAL Human 1,3β-D-Glucan but it was not statistically significant based on age and sex in the immunocompromised and immunocompetent groups (p = 0.632, p = 0.338, p = 0.472, p = 0.667).Conclusion: Patients suspected of lung cancer have risk factors for invasive candidiasis with higher BDG levels due to immunoparalysis. There were significant differences in the BAL Human levels of 1,3β-D-Glucan in the immunocompromised and immunocompetent groups.

Evaluation of the prognostic factors for candidemia in a medical intensive care unit

Aim: Infections with Candida species are an important cause of morbidity and mortality in intensive care units (ICUs). The studies about the prognostic factors related with candidemia in ICU patients are limited and lacking in our country. The aim of this study is to evaluate the epidemiology and prognostic factors for candidemia in adult patients admitted to a medical ICU. Methods: This is a retrospective cohort study. A total of 693 patients who were followed for more than 48 hours in our 16-bedded medical ICU between 2016 October-2019 March were evaluated retrospectively and 60 candidemia patients were included in the study. The patients were divided into two groups according to ICU mortality (survivor vs. non-survivor) and compared to determine possible prognostic factors among Candida infection risk factors. Results: The total incidence of candidemia was 46 per 1000 admissions. The most common fungal isolate was Candida albicans (57.5%). The 30-day mortality was 71.7% and ICU-mortality was 78.3%. There was no difference for age, gender, co-morbid diseases, SOFA and APACHE II scores, Glasgow Coma Score, immunosuppressive treatments (steroid or chemotherapy), septic shock, neutropenia, acute hepatic or renal failure, need for vasopressors, hemodialysis, erythrocyte transfusion and total parenteral nutrition between groups. No relationship was found between the time of initiation of antifungal therapy and mortality (P=0.268). Survivors had shorter ICU stay and hospital stay before ICU, and lower Charlson Comorbidity Index scores than non-survivors (P=0.039, P=0.008, P=0.02, respectively). Length of hospital stay before ICU, need for invasive mechanical ventilation and hypoalbuminemia were the prognostic factors for ICU mortality of candidemia patients (P=0.034, P=0.013, P=0.029, respectively). Conclusion: We reported the highest incidence rate of candidemia and one of the highest mortality rates in critically ill patients with candidemia. Confirming to most of the previous reports, Candida albicans (57.5%) was the most common isolate in our study. We evaluated reported risk factors for invasive candidiasis as a prognostic indicator for candidemia in ICU patients, and found that the length of hospital stay, invasive mechanical ventilation and hypoalbuminemia were prognostic indicators.

Role of Antifungal Therapy in Complicated Intra-abdominal Infections

In this narrative review, we discuss key questions about the antifungal treatment of complicated intrabdominal infections (cIAI). Although less common than bacteria, Candida spp. are not an infrequent cause of cIAI. Considering that invasive abdominal candidiasis (IAC) may be accompanied by septic shock in up to 40% of cases, empirical antifungal treatment should be considered while waiting for rapid tests and cultures results, and it should be guided by the presence of risk factors for invasive candidiasis in patients with consistent signs and symptoms. Early antifungal therapy before availability of culture results can be partly based on the results of rapid diagnostic tests such as antigen/antibody assays or other rapid methods, although it should be noted that most data pertaining to the use of rapid tests refer to candidemia or invasive candidiasis in general, and not specifically to IAC, thus clinical judgment still remains crucial. Although cultures are hampered by a slow turnaround time, they remain of paramount importance, by allowing identification at species level and antifungal susceptibility testing. Together with source control, adequate antifungal therapy is an essential component of the correct approach to IAC. Future research should focus on enriching our knowledge on the diagnostic performance of rapid tests in cIAI, and on providing a standardized definition for IAC. Advancements in these fields are crucial for improving the correct use of antifungals at the bedside of cIAI patients and also for reducing unnecessary antifungal use in line with antifungal stewardship principles.

Criteria for the administration of systemic antimicotic therapy in surgical intensive care units (literature review)

This review focuses on the practical aspects of prevention and treatment of fungal infections in surgical patients. It covers epidemiology and risk factors for invasive candidiasis, updates on the etiological structure of fungal infections in patients in critical conditions, and provides the information on drug sensitivity of Candida species. The authors discuss the limitations of cultural and non-cultural diagnostic methods used in invasive candidiasis, emphasizing the importance of analyzing the existing risk factors in combination with a comprehensive assessment of clinical and laboratory data for timely initiation of adequate antifungal therapy. The review provides a brief description of currently available antimicotics, including polyenes, triazoles, and echinocandins. It also describes the benefits of anidulafungin, which does not interact with other drugs and has no negative effect on the liver and kidney. The article also covers indications for antifungal agents in surgical intensive care units in accordance with international and Russian guidelines. A cohort of patients with abdominal diseases requiring preventive and empirical treatment with antimicotics is described. In additions to that, the manuscript contains a rationale for the use of echinocandins in targeted therapy of invasive candidiasis.

Diagnostic Performance of T2Candida Among ICU Patients With Risk Factors for Invasive Candidiasis.

BackgroundInvasive candidiasis (IC) comprises candidemia and deep-seated candidiasis. Blood culture (BC) is the gold standard test, but sensitivity is low. T2Candida is a new diagnostic test. We investigated the performance of T2Candida, BC, and Candida mannan antigen (MAg) for detection of IC in a high-risk intensive care unit (ICU) population.MethodsOne-hundred twenty-six ICU patients at high risk of IC with sepsis despite 3 days of broad-spectrum antibiotics were included. Paired BC, T2Candida, and MAg were obtained twice weekly (334 sets). Patients were classified into proven, likely, possible, or unlikely IC based on patient record review.ResultsAt enrollment, 92 (77%) patients were receiving antifungal therapy (mainly fluconazole 66%). Fifteen (11.9%) patients were positive by BC (n = 4), T2Candida (n = 11), or MAg (n = 10). The T2Candida species distribution at inclusion (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]) was supported by the identification of BC or colonizing isolates in 10/11 cases. Patients were classified with proven (11), likely (6), possible (11), and unlikely (98) IC. Defining IC as proven/proven&likely/proven&likely&possible, respectively, the sensitivity was as follows: T2Candida (55%/59%/39%), BC (45%/29%/ 8%), and MAg (36%/41%/32%). The negative predictive value was similar across the tests for proven vs others and proven/likely vs others (94%–96% and 90%–95%, respectively). For test combinations including T2Candida, the sensitivity increased to 64%–65%, without hampering the positive predictive value.ConclusionsIn conclusion, although the diagnostic performance was modest for all the tests, the combination of T2Candida and BC seemed to have the best diagnostic performance, and thus implementation of T2Candida may improve the diagnosis of IC.

Postoperative Hepatobiliary Surgeries' Fungal Infections Epidemiology: Prevalence and Risk Factors

AbstractBackground: Candidemia and disseminated candidiasis are major causes of morbidity and mortality in hospitalized patients especially in ICU, the incidence of invasive candidiasis is on a steady rise because of increasing use of multiple antibiotics and invasive procedures carried out in the ICUs. Risk factors for invasive candidiasis & candidaemia include prior antimicrobial therapy, central venous catheters, urinary catheters, ICU admission, parenteral nutrition, major surgery and immunosuppressive therapies. Candida species were the most frequently isolated organism from any sites and comprise 85% of total number of cultures.Aim of Study: Assessing the rate of fungal infections after hepatobiliary surgery and identification of the risk factors associated with the development of fungal infections in such patients.Patients and Methods: A prospective cohort hospital based study was carried out at National Liver Institute. The studied group consisted of 210 patients. All of them were examined thoroughly, their data were registered and sampled at two times, one at day of admission to be sure that they are free of fungal infection and the second was after hepatobiliary surgery pre-designed questionnaire was used which include data about personal history, medical history and suggested risk factors for fungal infections.Results: In the present study the incidence rate of fungal infection among patients undergone hepatobiliary surgeries in NLI is (45.2%) and the main predictors of fungal infection were age (p-value 0.001), antibiotic use (p-value 0.05), liver disease (p-value 0.006), CVC (p-value 0.043), urinary catheter (p-value 0.05), and ICU hospitalization more than 48 hours (p-value 0.000008).Conclusions: High incidence of fungal infection after hepatobiliary surgeries may reach 45% due to type of patient doing such surgeries. The great prevalence of fungal coloni-zation inside ICU which is easily transmissible emphasizes very strongly on the importance of infection- control guidelines.Recommendations: Aggressive antibiotics shouldn't be used outside ICU and only antibiotics according to culture and sensitivity should be used to lessen down emergence of resistant strains and fungal flourishment.

Evolution in the Management of Invasive Fungal Infections in Liver Transplant Recipients

Invasive fungal infections (IFI) remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. The incidence of IFIs has been declining in liver transplant recipients (LTR). This is likely due to the evolving immunosuppressive drug regimens, improved surgical techniques and targeted antifungal prophylaxis. However, these still contribute to high mortality and are associated with high economic burden due to consumption of costly newer antifungal agents, longer hospital stay and need of intensive supportive care. Candida remains the most common fungal infection in LTR. Antifungal prophylaxis in LTR at high risk of developing IFI is widely agreed on, but there is no universal consensus on treatment selection and duration. Fluconazole and echinocandins are recommended for prophylaxis, but is increasingly associated with resistance. Risk factors for invasive candidiasis (IC) and invasive aspergillosis (IA) continue to evolve, and thus strategies for their prevention should be constantly updated and targeted. What is clear, however, is that antifungal prophylactic strategy should be selected by the transplant centre based on risk factors for IFIs in their patients, local epidemiology, the sensitivity profile of local fungal pathogens, and drug costs. The treatment with echinocandin is recommended for IC, although the risk of breakthrough infections for intra-abdominal candida infections should be recognised. The recommended treatment for IA is voriconazole. Although many non-culture methods are available for the diagnosis of IFI, there is a need for further evaluation of these tests in LTR and antifungal stewardship (AFS).

Reemergence of Intravenous Drug Use as Risk Factor for Candidemia, Massachusetts, USA.

The epidemic of illicit intravenous drug use (IVDU) in the United States has been accompanied by a surge in drug overdose deaths and infectious sequelae. Candida albicans infections were associated with injection of contaminated impure brown heroin in the 1970s-1990s; however, candidiasis accompanying IVDU became considerably rarer as the purity of the heroin supply increased. We reviewed cases of candidemia occurring over a recent 7-year period in persons >14 years of age at a tertiary care hospital in central Massachusetts. Of the 198 patients with candidemia, 24 cases occurred in patients with a history of IVDU. Compared with non-IVDU patients, those with a history of IVDU were more likely to have non-albicans Candida, be co-infected with hepatitis C, and have end-organ involvement, including endocarditis and osteomyelitis. Thus, IVDU appears to be reemerging as a risk factor for invasive candidiasis.

Frequency of Candida Species Isolated from Patients in Children’s Medical Center, Tehran, Iran

Background: Candida species originating from either endogenous or exogenous sources are one of the main causes of opportunistic infections. Colonization is an important independent risk factor for invasive candidiasis, and many patients admitted to neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU) are colonized with Candida species that may result in invasive candidiasis. Awareness among clinicians about various aspects of colonization is critical to optimal management. The aim of this study was to determine the frequency and species distribution of Candida strains isolated from predisposed patients hospitalized at Children’s Medical Center (CMC), Tehran, Iran. Methods: From June 2014 to June 2016, 347 Candida isolates were collected from 341 patients either hospitalized in different wards or referred as outpatients. The yeasts were identified by colony color characteristics using CHROMagar Candida medium and by amplification of the ITS1-5.8S rDNA-ITS2 region in DNA extracted from each isolate followed by analysis of species specific electrophoretic patterns of PCR products digested with the restriction enzyme MspI. Results: Of the 341 patients, 213 were males and 128 were females. Most samples were obtained from the 1 – 12-month age group, and the majority of samples represented urine (n = 182), throat swabs (n = 57), and stool samples (n = 53), respectively. The samples were mostly from patients in general wards. The most commonly isolated species was C. albicans (77%), followed by C. tropicalis (8.4%), C. parapsilosis (7.5%), C. glabrata (2.3%), C. kefyr (1.7%), C. krusei (1.1%), C. lusitaniae (0.6%), C. guilliermondii (0.3%), C. albicans + C. parapsilosis (1.4%), and C. albicans + C. glabrata (0.3%). Conclusions: C. albicans is the most common species isolated from children in Iran, followed by C. tropicalis and C. parapsilosis, a prevalence pattern that is relatively different from studies in other countries. Neonates and infants 1 - 12 months of age hospitalized in ICU, were more colonized by Candida species than other groups.

Candida vertebral osteomyelitis (CVO) 28 cases from a 10-year retrospective study in France.

Although increasingly frequent, little is known about the clinical presentation, radiological signs, and outcome of Candida vertebral osteomyelitis (CVO).We performed a nationwide retrospective study of laboratory-confirmed cases of CVO over a 10 year-period in France with a prolonged follow-up. We describe demographic, clinical, biological, and radiological characteristics of patients with CVO, patients’ management, and long-term outcome and determine factors associated with a poor outcome.In total, 28 patients with laboratory-confirmed CVO were included. A prior systemic Candida infection was evidenced in 13/28 (46%), occurring a median of 6 weeks before CVO was diagnosed. Twenty-six of 28 (93%) had at least 1 underlying condition at risk of invasive fungal disease, and in 19/28 (68%) CVO was health-care related. C albicans was most frequently identified (21/28; 75%) Lumbo-sacral involvement was the most prevalent (20/28—71%). Nearly half patients had no fever at presentation, but all had pain. Initial antifungal therapy consisted in fluconazole in 15/28 (53%); surgery was needed in 5 (18%) cases.One-year mortality was 21% (6/28), directly related to fungal infection in 2 patients. Risk-factors associated with 1-year mortality were age (P=.02), a high Charlson comorbidity index (P = .001), and a shorter treatment duration (median, 3 months vs 6 months; P = .02). Among 22 patients who survived, the median follow up duration was 15.5 months (8–93.5); 10 had sequelae, consisting in pain in all and neurological deficit in one. A longer treatment duration was significantly associated with healing without sequelae (P = .04).CVO concerns patients with serious underlying conditions and risk-factors for invasive candidiasis. Prolonged antifungal treatment appears to improve survival without sequelae.

External Validation of Risk Prediction Scores for Invasive Candidiasis in a Medical/Surgical Intensive Care Unit: An Observational Study.

Background:The aim of this study was to conduct external validation of risk prediction scores for invasive candidiasis.Methods:We conducted a prospective observational study in a 12-bedded adult medical/surgical Intensive Care Unit (ICU) to evaluate Candida score >3, colonization index (CI) >0.5, corrected CI >0.4 (CCI), and Ostrosky's clinical prediction rule (CPR). Patients' characteristics and risk factors for invasive candidiasis were noted. Patients were divided into two groups; invasive candidiasis and no-invasive candidiasis.Results:Of 198 patients, 17 developed invasive candidiasis. Discriminatory power (area under receiver operator curve [AUROC]) for Candida score, CI, CCI, and CPR were 0.66, 0.67, 0.63, and 0.62, respectively. A large number of patients in the no-invasive candidiasis group (114 out of 181) were exposed to antifungal agents during their stay in ICU. Subgroup analysis was carried out after excluding such patients from no-invasive candidiasis group. AUROC of Candida score, CI, CCI, and CPR were 0.7, 0.7, 0.65, and 0.72, respectively, and positive predictive values (PPVs) were in the range of 25%–47%, along with negative predictive values (NPVs) in the range of 84%–96% in the subgroup analysis.Conclusion:Currently available risk prediction scores have good NPV but poor PPV. They are useful for selecting patients who are not likely to benefit from antifungal therapy.

Screening the Pathogen Box for Identification of Candida albicans Biofilm Inhibitors.

Candida albicans remains the main causative agent of candidiasis, one of the most frequent nosocomial infections, with unacceptably high mortality rates. Biofilm formation is a major risk factor for invasive candidiasis, as Candida biofilms display high-level resistance to most antifungal agents. In this work we have screened the Pathogen Box chemical library (Medicines for Malaria Venture [MMV], Switzerland) in search for inhibitors of C. albicans biofilm formation. Our initial screen identified seven hits, and additional dose-response assays confirmed the biofilm-inhibitory activity of six of these small molecules. Three compounds, MMV688768, MMV687273, and MMV687807, were also able to reduce the metabolic activity of cells within preformed biofilms. Interestingly, the most potent of these, compound MMV688768, displayed increased antibiofilm activity compared to its activity against planktonic cultures, indicating that it may affect processes with a predominant role during the biofilm mode of growth. This compound demonstrated a high selectivity index when its antibiofilm activity was compared with its toxicity in liver hepatocellular cells. In vitro combination assays showed a synergistic interaction between compound MMV688768 and fluconazole against preformed biofilms. Overall, our results indicate that this compound may constitute a potential candidate for further clinical development.

Evaluation of the Treatment of Candiduria at an Academic Medical Center.

To evaluate the epidemiology, management, and outcomes associated with candiduria in intensive care unit (ICU) and medical ward (MW) patients. This was a retrospective cohort study conducted in a tertiary care academic medical center. Adult patients aged between 18 and 75 years who were admitted for at least 5 days with a urinary culture that grew a Candida species between July 2010 and June 2011 were included. Medical records were retrospectively reviewed. Laboratory data, urinary symptoms, risk factors for urinary and invasive candidiasis, treatment, and patient outcomes were collected and evaluated. Sixty-seven ICU and 65 MW patients met the inclusion criteria. ICU patients were more likely to have risk factors for invasive candidiasis and candiduria. Candida albicans and Candida glabrata were the most frequently identified urinary isolates. Antifungal therapy was commonly initiated despite rapid replacement or removal of urinary drainage devices and a lack of patient reported symptoms. Fluconazole was the most commonly used antifungal agent, followed by micafungin. Hospital length of stay did not vary significantly between the ICU and MW groups (P = 0.0628). All-cause mortality was higher in the ICU patients compared with that of the MW patients (22.4% vs. 3.1%, P = 0.0012). Differences exist between ICU and MW patients that develop candiduria with respect to risk factors, and outcomes. Antifungals, including fluconazole and micafungin, were often used inappropriately (ie, asymptomatic patients) in this patient cohort. Efforts to improve healthcare provider awareness of the contemporary recommendations to manage candiduria are necessary to improve patient care and antifungal use.