Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients

Petri, Margit; König, J.; Moecke, H.; Gramm, H.-J.; Barkow, H; Kujath, P.; Dennhart, R; Schäfer, H.; Meyer, Norman; Kalmár, P.; Thülig, P; Müller, J.; Lode, H.

doi:10.1007/s001340050334

Cited by 167 publications

(85 citation statements)

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“…Incidence rates of critical care unit candidaemia in previous studies have varied from 1.1 to 94 cases per 1000 admissions, depending upon the geographic location of the unit, setting and inclusion criteria for the study. 25,[51][52][53][54][55][56] The rate of IFD in blood in the present study, at 3.5 per 1000 admissions, is similar to that of other European critical care units. 51,54,57 A previous hospital-wide surveillance from six sentinel hospitals in the UK identified that 45% of candidaemia was reported from the critical care unit, corresponding with an incidence of 7.4 per 1000 admissions.…”

Section: Discussionsupporting

confidence: 76%

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: Discussionsupporting

confidence: 76%

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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“…Its isolation from clinical specimens is generally considered as a contaminant. Of the 14 species of Aureobasidium known to date, A. pullulans is the best known to clinical mycologists, since it has been indicated as a rare etiologic agent of pheohyphomycosis, keratomycosis, septicemia, peritoneal sepsis, and dermatological infections (6,9,11,12,13,14,15,16).…”

mentioning

confidence: 99%

Disseminated Nosocomial Fungal Infection by Aureobasidium pullulans var. melanigenum : a Case Report

Bolignano

Criseo

2003

J Clin Microbiol

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We report on a rare case of disseminated nosocomial fungal infection due to Aureobasidium pullulans var. melanigenum in a severely traumatized patient. Repeated blood and urine cultures yielded multicellular filamentous hyphal structures of varying size accompanied by budding yeast-like-cells of ellipsoidal morphology. The patient became asymptomatic after fluconazole therapy. CASE REPORTThe patient, a 28-year-old male, was admitted to the intensive care unit of the Ospedali Riuniti of Reggio Calabria, Reggio Calabria, Italy, following multiple traumas due to a road accident. The patient suffered a head trauma and had a Glasgow coma scale rating of III-IV. After initial treatment with standard life support measures to stabilize hemodynamic and respiratory parameters, the patient underwent a total-body computed tomography scan, which showed diffuse cerebral edema, hemoperitoneum, multiple fractures of the left femur and tibia, a suspected pelvic fracture, and multiple ruptures of the liver's right lobe, which made immediate surgery mandatory. After surgery, the patient underwent mechanical ventilation and prolonged total parenteral nutrition.Following the isolation of a methicillin-resistant strain of Staphylococcus epidermidis from a blood culture (BCB-Slide system; Roche Products Pty. Ltd.) antibiotic therapy was started, with teicoplanin at 800 mg/day plus vancomycin at 2 g/day, divided into two doses daily. Four days later, following the onset of dyspnea and fever (37.5 to 38°C), a pulmonary infection was suspected. Laboratory data included a total leukocyte count of 10.7 ϫ 10 9 /liter with 70% neutrophils, 26% lymphocytes, and 4% monocytes. Microbiological examination of a bronchial aspirate showed the presence of Acinetobacter anitratus var. anitratus. Antibiotic therapy was therefore changed, replacing teicoplanin with ceftazidime pentahydrate at 4 g/day. After an initial decrease in body temperature lasting 3 days, fever increased again to 40°C. Therefore, a new blood culture was carried out, leading to the isolation of Pseudomonas aeruginosa. On the basis of antibiogram results, antibiotic treatment was changed again, with aztreonam at 6 g/day plus tobramycin at 300 mg/day, divided into three doses daily. Six days later, since fever was stable at around 38°C and the patient's condition was not improving, new cultures from blood and urine were made. After 72 h of incubation, the blood culture became diffusely turbid and several smooth and mucoid colonies appeared on agar growth media (chocolate agar and malt agar) enclosed in the BCB-Slide Roche system (Fig. 1). The urine culture, in contrast, was negative.Microscopic examination of fungal cultures revealed multicellular filamentous hyphal structures of varying size accompanied by budding ellipsoidal yeast-like cells, both in the blood culture and in the colonies growing on agar media. These fungal isolates were subsequently classified as Aureobasidium pullulans.Immediately before starting antifungal therapy, a new set of blood and urine cultures and a cu...

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“…Triazoles interfere with cell membrane formation through inhibiCan J In fect Di s Vol 8 Su ppl B July/A ugust 1997 tion of ergosterol synthesis and are fungi sta tic. Resistance to C glabrata , C krusei and C albicans has been reported (26,33). In a recent study by Rex et a l (34), amphotericin Band flucona zole had equal efficacy (in 206 candidemic patients) , and there was less toxicity with fluconazole .…”

Section: Fluconazolementioning

confidence: 98%

Guidelines for the Management of NosocomialCandidaInfections in Non-Neutropenic Intensive Care Patients

Demajo¹,

Guimond²,

Rotstein³

et al. 1997

Canadian Journal of Infectious Diseases

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A consensus meeting of the Canadian Candidemia Advisory Group was held during the 16th International Symposium on Intensive Care and Emergency Medicine on March 19, 1996 in Brussels, Belgium. For this meeting, a group of 20 intensive care and infectious disease specialists were brought together to discuss the risk factors associated withCandidaspecies colonization in intensive care units and the treatment of invasive candidiasis in nonneutropenic patients. Members of the consensus group assessed the evidence available and attempted to reach a consensus on the role of antifungal therapy in the intensive care unit setting.

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Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients

Cited by 167 publications

References 31 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

Disseminated Nosocomial Fungal Infection by Aureobasidium pullulans var. melanigenum : a Case Report

Guidelines for the Management of NosocomialCandidaInfections in Non-Neutropenic Intensive Care Patients

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