Candidemia in intensive care unit patients: Risk factors for mortality

Voß, Andreas; Noble, John; Lunel, F.; Foudraine, Norbert A.; Meis, Jacques F.

doi:10.1007/bf02113499

Cited by 130 publications

(77 citation statements)

References 19 publications

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“…59 Crude mortality in the present study was generally lower than reported in the literature for admissions to a critical care unit with IFD. 51,54,57,62 The reported crude mortality varied from 48% to 58%, whereas the acute hospital mortality in the present study was 40%. The discrepancy in mortality rates may be accounted for by differences in case mix, secular variation in critical care therapies or rates of fungal prophylaxis.…”

Section: Discussioncontrasting

confidence: 61%

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study

Harrison

Muskett

Harvey

et al. 2013

Health Technol Assess

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BackgroundThere is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy.ObjectivesTo develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasiveCandidainfection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models.DesignSystematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis.SettingNinety-six UK adult general critical care units.ParticipantsConsecutive admissions to participating critical care units.InterventionsNone.Main outcome measuresInvasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasiveCandidainfection, defined as IFD-positive forCandidaspecies.ResultsSystematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection.Data collection: Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive forCandidaspecies. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions.Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample.Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small. Incremental costs of the prophylaxis strategies compared with current practice were positive for most strategies, although a few strategies were cost saving. Incremental net benefits of each prophylaxis strategy compared with current practice were positive for most, but not all, of the strategies. Cost-effectiveness acceptability curves showed that risk assessment and prophylaxis at the end of calendar day 3 was the strategy most likely to be cost-effective when the risk threshold was 1% or 2%. At a lower risk threshold (0.5%) it was most cost-effective to assess risk at each time point; this led to a relatively high proportion of patients receiving antifungal prophylaxis (30%), which may lead to additional burden from increased resistance. The estimates of cost-effectiveness were highly uncertain and the value of further research for the whole population of interest is high relative to the research costs.ConclusionsThe results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at ‘high risk’ of invasiveCandidainfection. Results of the economic model suggested that the current most cost-effective treatment strategy among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of risk assessment and antifungal prophylaxis at the end of calendar day 3, but this finding is highly uncertain and future studies should consider the potential impact of increased resistance.FundingFunding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.A previous version of this report was published in February 2013. The report was subsequently modified to reflect a substantial reduction in the unit cost of fluconazole that took place between the original analysis being conducted and the publication of the report.

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Section: Discussioncontrasting

confidence: 61%

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study

Harrison

Muskett

Harvey

et al. 2013

Health Technol Assess

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“…The incidence of life-threatening hematogenously disseminated candidiasis, which is predominantly caused by C. albicans, is especially problematic in immunocompromised people ranging from premature infants to AIDS sufferers (1,15,49). The choice of anti-Candida drugs is limited, they may adversely affect the host, and the emergence of drug resistance is of potential importance (3,15,26,47). Difficulties often associated with both the diagnosis and treatment (2,14) support the development of new therapeutic and preventive strategies against candidiasis.…”

mentioning

confidence: 99%

Hybridoma Passage In Vitro May Result in Reduced Ability of Antimannan Antibody To Protect against Disseminated Candidiasis

Xin

Cutler

2006

Infect Immun

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We previously reported the enhanced resistance of monoclonal antibodies B6.1 (an immunoglobulin M [IgM]) and C3.1 (an IgG3) against experimental candidiasis. Both MAbs recognize the same fungal epitope. We have since found that a highly passaged B6.1 hybridoma (hp-B6.1) resulted in antibody that has little protective potential. The potential clinical applicability of the antibody and our interest in understanding antibody protection against candidiasis led us to investigate an explanation for this phenomenon. Antibody genetic structure of hp-B6.1, the original hybridoma clone (ori-B6.1) stored frozen since 1995, a subclone of hp-B6.1 that produces protective antibody, the IgG3-producing hybridoma, and a nonprotective IgG1-producing hybridoma were compared. Variable region gene sequences of heavy (V H ) and light chains showed genetic instability of V H chains with only the hp-B6.1; the V H sequences from ori-B6.1 and the subclone were, however, identical. Activation-induced cytidine deaminase levels were greatest in the B6.1 hybridomas, which may explain the instability. The constant region CH3 domain remained unchanged, implying normal N-glycation and complement-fixing potential, and antibody binding affinities appeared unchanged. Complement fixation assays surprisingly showed that ori-B6.1 antibody fixes C3 more rapidly than does hp-B6.1 antibody. The V H region primary structure may affect complement activation, which could explain our result. Indeed, antibody from the hp-B6.1 subclone fixed complement like antibody from ori-B6.1. These results show that the greatest protection occurs when antimannan antibodies possess the dual abilities of recognizing the appropriate carbohydrate epitope and rapidly fixing complement; loss of the latter property results in the loss of protective potential by the antibody.

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“…These opportunistic pathogens are often isolated from critically ill patients on intensive care units (ICUs), e.g., patients receiving broad-spectrum antimicrobial therapy or patients with intravascular devices (28,42). Candida species are the fourth most commonly encountered nosocomial pathogens in bloodstream infections in the United States, and candidiasis is associated with high mortality rates (5,14,17,31,43). Of the Candida species encountered in clinical practice, Candida albicans is the most prevalent.…”

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confidence: 99%

Rapid Identification ofCandidaSpecies by Confocal Raman Microspectroscopy

et al. 2002

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Candida species are important nosocomial pathogens associated with high mortality rates. Rapid detection and identification of Candida species can guide a clinician at an early stage to prescribe antifungal drugs or to adjust empirical therapy when resistant species are isolated. Confocal Raman microspectroscopy is highly suitable for the rapid identification of Candida species, since Raman spectra can be directly obtained from microcolonies on a solid culture medium after only 6 h of culturing. In this study, we have used a set of 42 Candida strains comprising five species that are frequently encountered in clinical microbiology to test the feasibility of the technique for the rapid identification of Candida species. The procedure was started either from a culture on Sabouraud medium or from a positive vial of an automated blood culture system. Prior to Raman measurements, strains were subcultured on Sabouraud medium for 6 h to form microcolonies. Using multivariate statistical analyses, a high prediction accuracy (97 to 100%) was obtained with the Raman method. Identification with Raman microspectroscopy may therefore be significantly faster than identification with commercial identification systems that allow various species to be identified and that often require 24 to 48 h before a reliable identification is obtained. We conclude that confocal Raman microspectroscopy offers a rapid, accurate, and easy-to-use alternative for the identification of clinically relevant Candida species.

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Candidemia in intensive care unit patients: Risk factors for mortality

Cited by 130 publications

References 19 publications

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study

Hybridoma Passage In Vitro May Result in Reduced Ability of Antimannan Antibody To Protect against Disseminated Candidiasis

Rapid Identification ofCandidaSpecies by Confocal Raman Microspectroscopy

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