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Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients

Overview of attention for article published in Cochrane database of systematic reviews, January 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

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49 tweeters
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3 Facebook pages

Citations

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56 Dimensions

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205 Mendeley
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Title
Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients
Published in
Cochrane database of systematic reviews, January 2016
DOI 10.1002/14651858.cd004920.pub3
Pubmed ID
Authors

Andrea Cortegiani, Vincenzo Russotto, Alessandra Maggiore, Massimo Attanasio, Alessandro R Naro, Santi Maurizio Raineri, Antonino Giarratano

Abstract

Invasive fungal infections are important causes of morbidity and mortality among critically ill patients. Early institution of antifungal therapy is pivotal for mortality reduction. Starting a targeted antifungal therapy after culture positivity and fungi identification requires a long time. Therefore, alternative strategies (globally defined as 'untargeted antifungal treatments') for antifungal therapy institution in patients without proven microbiological evidence of fungal infections have been discussed by international guidelines. This review was originally published in 2006 and updated in 2016. This updated review provides additional evidence for the clinician dealing with suspicion of fungal infection in critically ill, non-neutropenic patients, taking into account recent findings in this field. To assess the effects of untargeted treatment with any antifungal drug (either systemic or nonabsorbable) compared to placebo or no antifungal or any other antifungal drug (either systemic or nonabsorbable) in non-neutropenic, critically ill adults and children. We assessed effectiveness in terms of total (all-cause) mortality and incidence of proven invasive fungal infections as primary outcomes. We searched the following databases to February 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), and EMBASE (OVID). We also searched reference lists of identified studies and major reviews, abstracts of conference proceedings, scientific meetings and clinical trials registries. We contacted experts in the field, study authors and pharmaceutical companies as part of the search strategy. We included randomized controlled trials (RCTs) (irrespective of language or publication status) comparing the use of untargeted treatment with any antifungal drug (either systemic or nonabsorbable) to placebo, no antifungal, or another antifungal agent in non-neutropenic critically ill participants. Three authors independently applied selection criteria, extracted data and assessed the risk of bias. We resolved any discrepancies by discussion. We synthesized data using the random-effects model and expressed the results as risk ratios (RR) with 95% confidence intervals. We assessed overall evidence quality using the GRADE approach. We included 22 studies (total of 2761 participants). Of those 22 studies, 12 were included in the original published review and 10 were newly identified. Eleven trials compared the use of fluconazole to placebo or no antifungal treatment. Three trials compared ketoconazole versus placebo. One trial compared anidulafungin with placebo. One trial compared caspofungin to placebo. Two trials compared micafungin to placebo. One trial compared amphotericin B to placebo. Two trials compared nystatin to placebo and one trial compared the effect of clotrimazole, ketoconazole, nystatin and no treatment. We found two new ongoing studies and four new studies awaiting classification. The RCTs included participants of both genders with wide age range, severity of critical illness and clinical characteristics. Funding sources from pharmaceutical companies were reported in 11 trials and one trial reported funding from a government agency. Most of the studies had an overall unclear risk of bias for key domains of this review (random sequence generation, allocation concealment, incomplete outcome data). Two studies had a high risk of bias for key domains. Regarding the other domains (blinding of participants and personnel, outcome assessment, selective reporting, other bias), most of the studies had a low or unclear risk but four studies had a high risk of bias.There was moderate grade evidence that untargeted antifungal treatment did not significantly reduce or increase total (all-cause) mortality (RR 0.93, 95% CI 0.79 to 1.09, P value = 0.36; participants = 2374; studies = 19). With regard to the outcome of proven invasive fungal infection, there was low grade evidence that untargeted antifungal treatment significantly reduced the risk (RR 0.57, 95% CI 0.39 to 0.83, P value = 0.0001; participants = 2024; studies = 17). The risk of fungal colonization was significantly reduced (RR 0.71, 95% CI 0.52 to 0.97, P value = 0.03; participants = 1030; studies = 12) but the quality of evidence was low. There was no difference in the risk of developing superficial fungal infection (RR 0.69, 95% CI 0.37 to 1.29, P value = 0.24; participants = 662; studies = 5; low grade of evidence) or in adverse events requiring cessation of treatment between the untargeted treatment group and the other group (RR 0.89, 95% CI 0.62 to 1.27, P value = 0.51; participants = 1691; studies = 11; low quality of evidence). The quality of evidence for the outcome of total (all-cause) mortality was moderate due to limitations in study design. The quality of evidence for the outcome of invasive fungal infection, superficial fungal infection, fungal colonization and adverse events requiring cessation of therapy was low due to limitations in study design, non-optimal total population size, risk of publication bias, and heterogeneity across studies. There is moderate quality evidence that the use of untargeted antifungal treatment is not associated with a significant reduction in total (all-cause) mortality among critically ill, non-neutropenic adults and children compared to no antifungal treatment or placebo. The untargeted antifungal treatment may be associated with a reduction of invasive fungal infections but the quality of evidence is low, and both the heterogeneity and risk of publication bias is high.Further high-quality RCTs are needed to improve the strength of the evidence, especially for more recent and less studied drugs (e.g. echinocandins). Future trials should adopt standardized definitions for microbiological outcomes (e.g. invasive fungal infection, colonization) to reduce heterogeneity. Emergence of resistance to antifungal drugs should be considered as outcome in studies investigating the effects of untargeted antifungal treatment to balance risks and benefit.

Twitter Demographics

The data shown below were collected from the profiles of 49 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 205 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 4 2%
United States 1 <1%
South Africa 1 <1%
United Kingdom 1 <1%
Unknown 198 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 44 21%
Researcher 26 13%
Student > Bachelor 25 12%
Other 21 10%
Student > Ph. D. Student 19 9%
Other 47 23%
Unknown 23 11%
Readers by discipline Count As %
Medicine and Dentistry 106 52%
Nursing and Health Professions 18 9%
Pharmacology, Toxicology and Pharmaceutical Science 11 5%
Social Sciences 8 4%
Immunology and Microbiology 4 2%
Other 23 11%
Unknown 35 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 26. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 April 2017.
All research outputs
#725,574
of 14,562,155 outputs
Outputs from Cochrane database of systematic reviews
#2,154
of 11,000 outputs
Outputs of similar age
#20,571
of 336,522 outputs
Outputs of similar age from Cochrane database of systematic reviews
#51
of 206 outputs
Altmetric has tracked 14,562,155 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,000 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.2. This one has done well, scoring higher than 80% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 336,522 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 206 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.