Risk For Invasive Candidiasis Research Articles

P159 The impact of COVID-19 pandemic on invasive Candida auris infections in Kuwait

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesTo evaluate the impact of the coronavirus disease (COVID-19) pandemic on the incidence of Candida auris invasive infections at a national level.MethodsThis is a laboratory-based, three years-period retrospective study. The demographic and mycological data were obtained from the mycology reference laboratory (MRL) active surveillance system. The number of C. auris blood isolates was retrieved for the following years: 2019, 2020, and 2021. C. auris blood isolates from all hospitals were sent to the MRL as part of patient care. Species-level identification was confirmed by chromogenic media, VITEK 2 yeast identification system, and/or MALDI-TOF MS (VITEK MS). Antifungal susceptibility was performed using Etest according to manufacturer instructions. The following antifungal agents were tested: amphotericin B, fluconazole, voriconazole, and caspofungin. If the strain was resistant or intermediate to caspofungin, other echinocandins (micafungin or anidulafungin) were tested for confirmation. Since there were no established clinical breakpoints for C. auris, tentative minimum inhibitory concentrations were used based on experts’ opinions. Incidence rates of COVID-19 during the years 2020 and 2021 (COVID-19) were obtained from the World Health Organization website. All data were numerically coded and labelled for each variable using Microsoft Excel (Version 16.57, 2021), then analyzed by SAS 9.4 (SAS Institute., USA). P-value <.05 was considered statistically significant.ResultsA total of 307 samples isolated from invasive infections were reported with C. auris in this study (50 in 2019, 102 in 2020, and 155 in 2021). The number of patients reported with C. auris invasive infection increased significantly (P <.05) from 50 in 2019 (pre-COVID-19) to 155 in 2021 (post-COVID-19). This was associated with the waves of the COVID-19 pandemic in Kuwait. Of 307 C. auris isolates tested, all were resistant to fluconazole. Resistance to amphotericin B and caspofungin was 29/307 (9%) and 3/285 (1%) respectively.ConclusionPatients infected with COVID-19 are at considerable risk of invasive candidiasis especially critically ill patients staying in ICU. The significant increase in C. auris invasive infections as seen during this pandemic clearly demonstrates the great ability of this opportunistic pathogen to cause secondary lethal infections among COVID-19 patients. In addition, the spread of C. auris among patients in care facilities results in outbreaks, which further compromises the health care services and threatens patient safety. Therefore, a greater understanding of its epidemiology and awareness among healthcare staff about its identification methods, antifungal resistance profile and infection control measures are essential to improve outcomes and prevent further hospital transmission.

Evaluation of targeted versus universal prophylaxis for the prevention of invasive fungal infections following lung transplantation.

Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR=4.32 (1.51-12.38), P=.0064. Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.

Risk of invasive candidiasis with prolonged duration of ICU stay: a systematic review and meta-analysis

ObjectiveThis study aimed to evaluate the duration of intensive care unit (ICU) stay prior to onset of invasive candidiasis (IC)/candidaemia.DesignSystematic review and meta-analysis.Data sourcesPubMed, Cochrane, Embase and Web of Science...

Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis.

The 1,3-beta-d-glucan (BDG) test is used for the diagnosis of invasive candidiasis (IC) in intensive care units (ICUs). However, its utility for patient management is unclear. This study assessed the impact of BDG test results on therapeutic decisions. This was a single-center observational study conducted in an ICU over two 6-month periods. All BDG test requests for the diagnosis of IC were analyzed. Before the second period, the ICU physicians received a pocket card instruction (algorithm) for targeted BDG testing in high-risk patients. The performance of the BDG test for IC diagnosis was assessed, as well as its impact on antifungal (AF) prescription. Overall, 72 patients had ≥1 BDG test, and 14 (19%) patients had an IC diagnosis. The BDG test results influenced therapeutic decisions in 41 (57%) cases. The impact of the BDG test was positive in 30 (73%) of them, as follows: AF abstention/interruption following a negative BDG result (n = 27), and AF initiation/continuation triggered by a positive BDG test result and subsequently confirmed IC (n = 3). In 10 (24%) cases, a positive BDG test result resulted in AF initiation/continuation with no further evidence of IC. A negative BDG result and AF abstention with subsequent IC diagnosis were observed in one case. The positive predictive value (PPV) of BDG was improved if testing was restricted to the algorithm's indications (80% versus 36%, respectively). However, adherence to the algorithm was low (26%), and no benefit of the intervention was observed. The BDG result had an impact on therapeutic decisions in more than half of the cases, which consisted mainly of safe AF interruption/abstention. Targeted BDG testing in high-risk patients improves PPV but is difficult to achieve in ICU.

What Is New in Candida Infections? T2Candida, Antifungal Stewardship, and Candida auris

We review T2Candida panel performance in diagnosing invasive candidiasis, potential roles of T2Candida, and other culture-independent tests in patient management and antifungal stewardship, and diagnosis and treatment of infections by Candida auris, which has emerged globally as a cause of nosocomial outbreaks. In 2 multicenter trials, T2Candida was 90% sensitive and 98% specific for diagnosing candidemia directly from whole blood samples. A subsequent study demonstrated T2Candida sensitivity/specificity of 45%/96% for diagnosing deep-seated candidiasis. Other studies have shown that ongoing T2Candida positivity was associated with poor patient outcomes, and T2Candida targeted to patients at risk for invasive candidiasis was useful in guiding antifungal treatment and stewardship decisions. C. auris is misidentified by commercial biochemical and matrix-assisted laser desorption ionization time-of-flight mass spectrometry systems that do not include the species in their databases. In different studies, a T2Candida research assay was 89% sensitive and 98% specific in identifying C. auris in clinical axilla or groin swab samples, and serum β-D-glucan sensitivity and specificity for diagnosing invasive infections by C. auris and other species were comparable. Fluconazole, amphotericin B, and echinocandin resistance rates among C. auris isolates are > 90%, ~ 30%–40%, and ~ 3%–10%, respectively. Echinocandins are agents of choice against most C. auris infections. Since T2Candida results assign a probability of invasive candidiasis based on pre-test disease likelihood, the test will only have value if directed toward at-risk patients. Rapid and accurate tests for detecting C. auris are needed for surveillance and diagnostic purposes.

Diagnosis of Fungal Infections. A Systematic Review and Meta-Analysis Supporting American Thoracic Society Practice Guideline

Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings.Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), β-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis).Methods: Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios.Results: Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64-0.78) and specificity of 0.89 (95% CI, 0.84-0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73-0.91) and specificity of 0.88 (95% CI, 0.81-0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73-0.86) and specificity of 0.79 (95% CI, 0.68-0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77-0.96) and specificity of 0.96 (95% CI, 0.93-0.98) for diagnosing IA. β-d-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74-0.86) and specificity of 0.60 (95% CI, 0.49-0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease).Conclusions: The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

EPICO 4.0. ‘Total quality’ in the management of invasive candidiasis in critically ill patients by analysing the integrated process

BackgroundA high quality integrated process in the clinical setting of non-neutropenic critically ill patients at risk for invasive candidiasis is a necessary tool to improve the management of these patients. AimsTo identify the key points on invasive candidiasis in order to develop a set of recommendations with a high level of consensus required for the creation of a total quality integrated process for the management of non-neutropenic critically ill patients at risk of invasive candidiasis. MethodsAfter a thorough review of the literature of the previous five years, a Spanish prospective questionnaire, which measured consensus by the Delphi technique, was anonymously conducted by e-mail, including 31 national multidisciplinary experts with extensive experience in invasive fungal infections, from six national scientific societies. The experts included a specialist in intensive care medicine, anesthetists, microbiologists, pharmacologists, and specialists in infectious diseases that responded 27 questions prepared by the coordination group. The educational objectives considered six processes that included knowledge of the local epidemiology, the creation and development of multidisciplinary teams, the definitions of the process, protocols, and indicators (KPI), an educational phase, hospital implementation, and the measurement of outcomes. The level of agreement among experts in each category to be selected should exceed 70%. In a second phase, after drawing up the recommendations of the selected processes, a face to face meeting with more than 60 specialists was held. The specialists were asked to validate the pre-selected recommendations. Measures and main outcomesFirstly, 20 recommendations from all the sections were pre-selected: Knowledge of local epidemiology (3 recommendations), creation and development of multidisciplinary teams (3), definition of the process, protocols and indicators (1), educational phase (3), hospital implementation (3), and measurement of outcomes (7). After the second phase, 18 recommendations were validated, and it was concluded that the minimum team or core necessary for the development of an efficient program in the use of antifungal drugs in non-neutropenic critically ill patients must consist of a specialist in infectious diseases, a clinical pharmacist, a microbiologist, a specialist in intensive care medicine, a specialist in anesthesia and recovery, and an administrator or member of the medical management team, and, in order to be cost-effective, it should be implemented in hospitals with over 200 beds. In addition, it is recommended to apply a consensual check list for the evaluation of the diagnostic process and treatment of invasive candidiasis in patients that have started an antifungal treatment. The management of external knowledge and individual learning stand out as active educational strategies. The main strategies for measuring patient safety outcomes are the analysis of the results achieved, and learning activities; assess, review and refine the deployment of the processes; quality control; epidemiological surveillance and applied research; benchmarking; and basic research. The results of the integrated process should be annually disseminated outside the hospital. ConclusionsOptimizing the management of invasive candidiasis requires the application of the knowledge and skills detailed in our recommendations. These recommendations, based on the Delphi methodology, facilitate the creation of a total quality integrated process in critically-ill patients at risk for invasive candidiasis.

Profil Candida Penyebab Kandidemia dan Pola Kepekaan terhadap Anti Jamur pada Pasien Sakit Kritis di Rumah Sakit Cipto Mangunkusuno

Candida spesies is important cause of nosocomial infection that lead to death and prolonged hospital stay. Guideline management of candidiasis by Infectious Diseases Society of America (IDSA) in 2009 proposed early antifungal therapy in critical patient with the risk of invasive candidiasis. Early identification of sepsis patien with high risk of fungal infection is challenging because long and low result from blood culture. Antifungal usage without appropriate indication can cause resistance to antifungal. The aim of the study is obtain data candida species that caused candidemia in Cipto Mangunkusuno hospital (RSCM) and sensitivity pattern to antifungal . This retrospective study used patient medical record from 2011-2014. This study had 117 candidemia case in RSCM during 2011-2014. Every year candidemia was dominated by Candida tropicalis, Candida albicans, and Candida parapsilosis with trend the increase number of Candida tropicalis since 2013. Susceptibility pattern of C andida that cause candidemia in RSCM from 71 isolat tested the result was86% spesies Candida flukonazol sensitive, 99% vorikonazol sensitive, 97% amfoterisin B sensitive and 100% flusitosin sensitive.

Antagonism of Fluconazole and a Proton Pump Inhibitor against Candida albicans.

Hospitalized ill patients, at risk for invasive candidiasis, often receive multiple medications, including proton pump inhibitors (PPIs). The antifungal fluconazole perturbs the vacuolar proton ATPase. The PPI omeprazole antagonized Candida albicans growth inhibition by fluconazole. A C. albicans codon-adapted pHluorin, Ca.pHluorin, was generated to measure cytosolic pH. The fungal cytosol was acidified by omeprazole and realkalinized by coexposure to fluconazole. Vacuolar pH was alkalinized by fluconazole. Off-target effects of any medication on fungal pathogens may occur.

Candida Score as a Predictor of Worse Outcomes and Mortality in Severely Injured Trauma Patients with Positive Candida Cultures

Invasive candidiasis is associated with worse outcomes and increased mortality in critically ill patients. The Candida score (CS) provides a clinical tool for identifying patients at risk for invasive candidiasis. Outcomes of severely injured trauma patients with positive candida cultures stratified by their CS have not been well described. In this retrospective observational study, all severely injured trauma patients (Injury Severity Score ≥16) admitted to the Los Angeles County and University of Southern California Medical Center from April 2008 to April 2014 with positive Candida cultures were included. Outcomes of patients with a low risk for invasive candidiasis (CS < 3) were compared with those with a high risk (CS ≥ 3). A CS ≥ 3 was significantly associated with higher mortality (35.9% vs 5.0%, P = 0.001), longer length of stay (LOS) (median 49.0 vs 28.0, P = 0.002), longer intensive care unit LOS (35.0 vs 20.0, P < 0.001), requirement for renal replacement therapy (38.5% vs 4.9%, P < 0.001), and increased ventilator days (22.0 vs 12.0, P < 0.001). Multivariable regression analysis revealed a CS ≥ 3 as a significant predictor for increased mortality [OR 6.983], longer LOS [regression coefficient (RC) 1.572] and intensive care unit LOS (RC 1.698), more frequent need for renal replacement therapy (OR 13.268), and increased ventilator days (RC 1.836). In conclusion, a CS ≥ 3 is significantly associated with increased mortality and worse outcomes in severely injured trauma patients with positive Candida cultures. The CS thus may serve as a clinical tool to predict outcomes in this patient population.

Candida colonization of respiratory tract: to treat or not to treat, will we ever get an answer?

In non-immunocompromised intensive care unit (ICU)patients Candida isolation from various sites is common[1]. The association with the risk of invasive candidiasis(IC) is the rational for the use of predictive scores whichinclude the colonization status.However the meaning of Candida spp. recovery fromthe lung is definitely more intriguing. Apart from ICepisodes occurring in deeply immunosuppressed subjectswho may develop true fungal pneumonia, Candidarespiratory tract (RT) isolation should not be considered amarker of lung infection. This issue was addressed byMeersseman et al. [2] who did not identify any autopsy-proven case of Candida pneumonia among 135 autopsieswith histopathological evidence of bacterial infection andhigh rate of Candida isolation from endotracheal aspirate(EA) and/or bronchoalveolar lavage (BAL) (57 %).However there is growing convincing evidence, basedon animal studies and human observations, that Candidaspp. is not definitely an innocent bystander in the respi-ratory tract of ICU ventilated patients [3–13] (Table 1).Beta-glucan (BG), a component of yeast cell wall, mayact as a lung proinflammatory agent causing alveolarmacrophage and neutrophil dysfunction. Additionally,within the environmental biofilm there is a strong inter-play, through quorum-sensing (QS) molecules, betweenand both Gram-positive and Gram-negativebacteria [14]. Live Candida albicans instillation in ratshas been observed to increase the susceptibility to developexperimental Pseudomonas aeruginosa (PA), Escherichiacoli (Ec), and Staphylococcus aureus (Sa) pneumonia,fostering the production of lung inflammatory cytokines(tumor necrosis factor alpha [TNF-alpha], interleukin-6[IL-6], and interferon-gamma [INF-c]) and inhibitingalveolar macrophage phagocytosis [3, 5]. From a clinicalviewpoint, Candida airway colonization has been shownto be associated with prolonged duration of mechanicalventilation, ICU/hospital length of stay, and increasedmortality [8–11]. One of the first reports of this possiblerelationship dates back to almost 10 years ago, whenAzoulay et al. [6] identified Candida bronchial isolationas an independent risk factor for the development of PAventilator-associated pneumonia (VAP) (9 vs 4.8 % innon-colonized patients, p = 0.048). These data werestrengthened just 1 year later by Nseir et al. [7] whoobserved a protective role of antifungal treatment on PAVAP occurrence in a cohort of patients with Candidatracheobronchial colonization. However, recently, the useof nebulized amphotericin B (NAB) was not able toprovide any clinical improvement, albeit increasing therate of Candida decolonization (adjusted HR 2.2; 95 %CI 1.6–3) [13]. Hence the clinical usefulness of respira-tory tract Candida colonization (CC) eradication inmechanically ventilated patients is still a matter of debateand the paper by Albert et al. [15] in the current issue ofIntensive Care Medicine is the first interventional trialaiming to describe the biochemical and clinical effect ofantifungal treatment in ICU patients with VAP and RTCc. In this double-blind, placebo-controlled, multicenterstudy 60 patients were enrolled: 29 in the placebo groupand 31 in the antifungal strategy group. A comparative

Clinical Practice Patterns in Hospitalized Patients at Risk for Invasive Candidiasis

Rapid diagnostic tests for Candida are becoming available that may supplement traditional microbiological identification. Assess clinical practice patterns in patients with or at risk of candidiasis who may benefit from the use of rapid diagnostic tests. This was a prospective cohort study of patients with candidemia or receiving systemic antifungals conducted at a university-affiliated tertiary care hospital. Time to initiation of therapy, Candida species, time to identification, and indications for antifungal use were assessed. A total of 162 patients with candidemia aged 58 ± 17 years were identified. Average time to yeast identification yeast was 2.2 ± 1.3 days and varied by Candida species (range = 0.6-7.9 days). Average time for patient to start antifungal therapy was 3.5 ± 2.1 days. In Monte Carlo simulations, average time to initiation of antifungal therapy was 0.6 ± 0.2 days for T2Candida, 2.6 ± 1.3 days for PNA-FISH (fluorescence in situ hybridization using peptide nucleic acid probes), and 2.5 ± 1.4 days for MALDI-TOF (matrix-assisted laser desorption/ionization time of flight). Use of T2Candida on the day of the blood culture collection resulted in 3136 to 6078 fewer doses of echinocandins annually per 5000 patients. Many interventions are possible for antifungal stewardship programs to improve care of patients at risk for systemic candidiasis, including rapid identification of yeast species and limiting unnecessary antifungal agents. Technology enabling rapid diagnosis of Candida will be paramount to appropriate, cost-effective treatment of patients with or at risk for candidiasis.

Nosocomial candiduria in chronic liver disease patients at a hepatobilliary center.

Sir, We read the article “Nosocomial candiduria in chronic liver disease patients at a hepatobiliary center”[1] with great interest. This article clearly highlights the importance of repeat sampling in patients who are reported as having candiduria. Candiduria can occur due to contamination, colonization (of the indwelling catheter or bladder), and infection (Candida cystitis or ascending pyelonephritis or renal candidiasis) as discussed in this article. Taking a repeat sample after insertion of fresh catheter eliminates the chances of contamination, but colonization can still be present without any clinical manifestation of disease.[2,3] Differentiation between the colonization and infection is difficult one and should be interpreted in the light of clinical features. Frequently, due to the presence of multiple co morbidities the line of demarcation between Candida colonization and infection is blurred, more so in critically ill patients. Pathogenesis of urinary tract and renal infections caused by Candida involves hematogenous spread as well ascending infection. When suspecting hematogenous spread various risk prediction scores (colonization index, Candida score) have been designed to guide therapy.[3,4] Candida colonization has been shown to be a risk factor for invasive candidiasis, but multiple site colonization and heavy colonization is considered more significant than single site colonization.[5] Candiduria represents single site colonization and should not trigger initiation of treatment unless other symptoms are also present. When suspecting ascending infection, one should look for predisposing factors like presence of stone or presence of obstruction, urinary drainage devices, prior surgical procedures, broad spectrum antibiotic use, old age, and diabetes mellitus. Infectious Disease Society of America 2009 guidelines recommends that asymptomatic candiduria should not be treated unless the patient is at high risk of invasive candidiasis (neutropenia, low birth weight, and patients who undergo urologic procedures).[6] The reason for treating asymptomatic candiduria in high risk patients is mainly prophylaxis. Chronic liver disease is a very broad terminology and includes various etiologies and stages of evolution in its natural history. Whether all chronic liver disease patients should be included in the high risk remains to be established. Currently, there is a paucity of literature regarding predisposition for invasive Candida infections among chronic liver disease patients. It would have been enlightening if the patient characteristics and stages/classification of liver disease were also mentioned in this study. The study also reports that 11 (3.5%) patients of candiduria evolved to candidemia. Though it is difficult to perform, genotypic identification is ideally required before one can say that species colonizing is the same as the species responsible for blood stream infection.

Prevalence of Candida colonization in preterm newborns and VLBW in neonatal intensive care unit: role of maternal colonization as a risk factor in transmission of disease

Candida species are important nosocomial pathogens in the newborn population, particularly among the premature very low birth weight (VLBW) infants in neonatal intensive care units (NICU). Candida colonization in neonates and subsequent dissemination result in a plenty of morbidity and mortality risks. This work aims to determine the prevalence of Candida species colonization in preterms and VLBW newborns in NICU in Al-Hasa, Kingdom of Saudi Arabia, and detect the relation of maternal colonization as a risk factor for transmitting the disease. Subjects and Methods: One hundred two preterms were included; 70 delivered vaginally (index cases) and 32 delivered by cesarean section (control group). Several swabs from oral, umbilical and anus were taken at birth, at third day and 1 week after birth. High vaginal swabs were also taken from the mother before labor. Results: Candida colonization was detected in 12.8% of index cases. Most of them (88.8%) were detected at the third day after birth. The initial site of colonization was the anus (88.8%) in comparison with oral cavity (66.6%) and the umbilicus (55%). Vaginal delivery and prolonged duration of premature rupture of membranes were significantly positively correlated to neonatal colonization (p < 0.02 and p = 0.02, respectively). The lowest birth weight, gestational age and uses of invasive techniques have the highest significant risk for colonization after birth (p < 0.04, p = 0.03 and p = 0.03, respectively). Candida albicans was the most common species detected (77.7% of the cases). The preterm’s colonization species were all identical to their mother vaginal colonization species. Invasive candidiasis was detected in 22.2% of colonized preterm. Conclusion: Candida colonization has a considerable prevalence among the preterms in our NICU. Besides vaginal delivery, low birth weight and low gestational age could be considered as risk factors for colonization. Early screening of the mothers with preterm labor for Candida and proper management help to avoid colonization with subsequent risk of invasive Candidiasis.

Design and use of Candida scores at the intensive care unit

Invasive Candida infections are recognised as a cause of increased morbidity and mortality in intensive care patients, particularly those with recent extensive gastroabdominal surgery. Due to the difficulties of diagnosis, several authors have analysed risk factors suggestive of invasive candidiasis to identify patients at highest risk. Such patients may be potential candidates for preemptive antifungal therapy before becoming seriously ill. The extent of body site colonisation due to Candida species was recognised to be related with consequent invasive disease. The quantification of the colonisation was expressed as the Candida colonisation index. Based on the evaluation of independent risk factors predictive of invasive Candida infections, clinically relevant scores were evaluated in the last decade. Particularly, the Candida score that combines the clinical risk factors preceding surgery, total parenteral nutrition and severe sepsis with Candida multi-site colonisation can be considered a useful bedside scoring system to discern patients with mere Candida colonisation from patients with the risk of invasive candidiasis in non-neutropaenic critically ill patient population.

Safety and Pharmacokinetics of Multiple-Dose Anidulafungin in Infants and Neonates

Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration-time curve (range) was 75 (30-109) µg·h/ml and 98 (55-278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug-related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight-based dosing and in adult patients receiving 100mg/day.

Is (1→3)-β-D-glucan the missing link from bedside assessment to pre-emptive therapy of invasive candidiasis?

Invasive candidiasis is a frequent life-threatening complication in critically ill patients. Early diagnosis followed by prompt treatment aimed at improving outcome by minimizing unnecessary antifungal use remains a major challenge in the ICU setting. Timely patient selection thus plays a key role for clinically efficient and cost-effective management. Approaches combining clinical risk factors and Candida colonization data have improved our ability to identify such patients early. While the negative predictive value of scores and predicting rules is up to 95 to 99%, the positive predictive value is much lower, ranging between 10 and 60%. Accordingly, if a positive score or rule is used to guide the start of antifungal therapy, many patients may be treated unnecessarily. Candida biomarkers display higher positive predictive values; however, they lack sensitivity and are thus not able to identify all cases of invasive candidiasis. The (1→3)-β-D-glucan (BG) assay, a panfungal antigen test, is recommended as a complementary tool for the diagnosis of invasive mycoses in high-risk hemato-oncological patients. Its role in the more heterogeneous ICU population remains to be defined. More efficient clinical selection strategies combined with performant laboratory tools are needed in order to treat the right patients at the right time by keeping costs of screening and therapy as low as possible. The new approach proposed by Posteraro and colleagues in the previous issue of Critical Care meets these requirements. A single positive BG value in medical patients admitted to the ICU with sepsis and expected to stay for more than 5 days preceded the documentation of candidemia by 1 to 3 days with an unprecedented diagnostic accuracy. Applying this one-point fungal screening on a selected subset of ICU patients with an estimated 15 to 20% risk of developing candidemia is an appealing and potentially cost-effective approach. If confirmed by multicenter investigations, and extended to surgical patients at high risk of invasive candidiasis after abdominal surgery, this Bayesian-based risk stratification approach aimed at maximizing clinical efficiency by minimizing health care resource utilization may substantially simplify the management of critically ill patients at risk of invasive candidiasis.

Assessing the Risk for Invasive Candidiasis in the ICU

Invasive fungal infections in critically ill patients are worrisome because diagnosis is difficult and the mortality rate is high. Researchers recently developed a “ Candida score” (CS) to assess the risk for invasive candidiasis (IC) in such patients. The score was calculated by assigning one point each for total parenteral nutrition, surgery, and multifocal Candida colonization and two points for severe sepsis. Now, the …

Simple and rapid detection of Candida albicans DNA in serum by PCR for diagnosis of invasive candidiasis.

A rapid and sensitive PCR assay for the detection of Candida albicans DNA in serum was established. DNA from human serum samples was purified using the QIAamp blood kit, which proved to be a fast and simple method for isolating minute amounts of Candida DNA from clinical specimens for diagnosis of invasive candidiasis. Universal primer sequences used in the PCR assay are derived from the internal transcribed spacer rRNA gene of fungi, whereas the biotinylated hybridization probe used in a DNA enzyme immunoassay (DEIA) binds specifically to C. albicans DNA. The sensitivity of this PCR-DEIA method is very high; the detection limit for genomic Candida DNA is one C. albicans genome per assay. Blood from uninfected and infected persons, ranging from healthy volunteers, patients with mucocutaneous infections, and patients at risk to develop a systemic Candida infection to patients with an established systemic candidiasis, was analyzed for the presence of C. albicans to diagnose fungal infection. Candida DNA could not be detected in sera of 16 culture-negative controls and from 11 nonsystemic candidal infections by PCR or DEIA. Blood cultures from patients at risk were all negative for Candida, whereas all blood cultures from systemic candidiasis patients were positive. However, Candida DNA could be detected by PCR and DEIA in the serum from three out of nine patients who were at risk for a systemic infection and in the serum of all seven patients who had already developed an invasive Candida infection. PCR is more sensitive than blood culture, since some of the patients at risk for invasive yeast infection, whose blood cultures were all negative for Candida, tested positive in the PCR amplification. These results indicate the potential value of PCR for detecting C. albicans in serum samples and for identifying patients at risk for invasive candidiasis.

Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum d-arabinitol

Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis. A total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups. A DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01). Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis.