Assessment of clinical risk predictive rules for invasive candidiasis in a prospective multicentre cohort of ICU patients

Playford, E. Geoffrey; Lipman, Jeffrey; Kabir, Masrura; McBryde, Emma S.; Nimmo, Graeme R.; Lau, Anna F.; Sorrell, Tania C.

doi:10.1007/s00134-009-1619-9

Cited by 54 publications

(44 citation statements)

References 16 publications

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“…Based on a cut-off of a score of 3, the sensitivity was 78% (81% in development data), specificity was 66% (74% in development data), and PPVs and NPVs were 14% and 98%, respectively (not reported in development data). Playford et al 46 validated four clinical decision rules -the best rule from Ostrosky-Zeichner et al 27 and a subsequent revision to this, published in abstract form, and the two best rules from Pittet et al 43 -in a prospective cohort of 615 patients admitted for at least 72 hours to four multidisciplinary ICUs in Australia. Performance of the clinical prediction rules was worse than in the development data sets and the authors recommended that to identify a sufficiently high-risk population to consider for antifungal therapy would require a combination of the clinical risk factors from Ostrosky-Zeichner et al 27 with measures of colonisation from Pittet et al 43 Most recently, Hermsen et al 47 set out to validate the clinical decision rules of Paphitou et al 28 and Ostrosky-Zeichner et al 27 in a case-control study of 88 cases and 264 matched control subjects staying at least 4 days in a single multidisciplinary ICU in the USA.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, no previous study has assessed the costeffectiveness of using a risk model to define a risk threshold above which to initiate antifungal prophylaxis for preventing invasive Candida infection in non-neutropenic, critically ill adult patients. 46 This chapter therefore presents an economic evaluation with the aim to report the relative costeffectiveness of alternative strategies to prevent invasive Candida infection for non-neutropenic, critically ill adult patients admitted to NHS critical care units. The objectives of the economic evaluation were to establish the relative cost-effectiveness of risk assessment using the FIRE Study risk models, followed by initiation of prophylaxis at different thresholds of baseline risk and at different time points; and to assess the relative value of further research to reduce uncertainty about the optimum strategy to adopt.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Using data from mixed medical/surgical ICUs in Australia, we demonstrated that the post hoc addition of colonization parameters to two published clinical risk factor-only predictive models improved their performance characteristics (17).…”

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confidence: 98%

“…Those rules have been applied in various settings and have included assessment at different times postadmission to the ICU and different types of ICU (surgical ICUs only or mixed medical/surgical ICUs-defined as units that house both medical and surgical populations). These differences may explain why predictive models and algorithms have performed poorly outside their derivative populations (17).…”

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confidence: 99%

Candida Colonization as a Risk Marker for Invasive Candidiasis in Mixed Medical-Surgical Intensive Care Units: Development and Evaluation of a Simple, Standard Protocol

et al. 2015

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k Colonization with Candida species is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candida colonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR] ‫؍‬ 2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of >2 sites and heavy colonization of >1 site were significant independent risk factors for IC (RR ‫؍‬ 2.25 and RR ‫؍‬ 3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC. Invasive candidiasis (IC), particularly, candidemia, is a significant cause of mortality in critically ill patients, accounting for almost a third of nosocomial infections in intensive care units (ICUs) (1, 2). Early antifungal therapy reduces IC-related mortality and approximately halves the incidence of IC (3-8). Untargeted prophylactic antifungal use, however, is expensive, has the potential to cause adverse drug reactions, and may select for resistant fungal species (9).Clinical risk prediction rules that identify the high-risk patients most likely to benefit from prophylaxis have been developed (10-16), but those studies have used different sets of predictors, including (a) clinical risk factors only and (b) clinical risk factors in combination with colonization indices (CIs). Those rules have been applied in various settings and have included assessment at different times postadmission to the ICU and different types of ICU (surgical ICUs only or mixed medical/surgical ICUs-defined as units that house both medical and surgical populations). These differences may explain why predictive models and algorithms have performed poorly outside their derivative populations (17).Since IC is pr...

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“…[7][8][9] These studies have focused on patients at high risk for IC and have included colonization sites other than the gastrointestinal tract. Additionally, the ability to include colonization with yeast in such a clinical prediction rule requires routine surveillance cultures, which are not performed at our institution.…”

Section: Conflict Of Interestmentioning

confidence: 99%

Is Incidental Recovery of Yeast from Enteric Pathogen Stool Cultures Obtained from Hospitalized Patients Clinically Significant?

Pfeifer

Iwen

Qiu

et al. 2011

Infectious Disease Reports

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A matched case-control study was conducted to investigate gastrointestinal colonization with yeast as a predictor of invasive candidiasis (IC) in patients who underwent an enteric pathogen test. No significant association was detected between gastrointestinal colonization and IC. However, gastrointestinal colonization with yeast was associated with increased antimicrobial exposure and median length of hospitalization.

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Assessment of clinical risk predictive rules for invasive candidiasis in a prospective multicentre cohort of ICU patients

Abstract: Risk predictive models should factor in both clinical risk factors and Candida colonisation parameters. Integrating these models into therapeutic algorithms first requires external validation in different patient populations and settings.

Cited by 54 publications

References 16 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

Candida Colonization as a Risk Marker for Invasive Candidiasis in Mixed Medical-Surgical Intensive Care Units: Development and Evaluation of a Simple, Standard Protocol

Is Incidental Recovery of Yeast from Enteric Pathogen Stool Cultures Obtained from Hospitalized Patients Clinically Significant?

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