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Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.

ABSTRACT: The potential of the systemic antifungal treatment of non-immunocompromised patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown, although it represents three out of four antifungal treatments prescribed in intensive care units. It may allow an early treatment of invasive fungal infection at incubation phase, but exposes patients to unnecessary antifungal treatments with subsequent costs and antifungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered insufficient, the potential of this strategy needs to be demonstrated by a randomized controlled trial. Such a trial is currently ongoing.

SUBMITTER: Timsit JF

PROVIDER: S-EPMC4335794 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.

Timsit Jean-François JF Chemam Sarah S Bailly Sébastien S

F1000prime reports 20150203

The potential of the systemic antifungal treatment of non-immunocompromised patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown, although it represents three out of four antifungal treatments prescribed in intensive care units. It may allow an early treatment of invasive fungal infection at incubation phase, but exposes patients to unnecessary antifungal treatments with subsequent costs and antifungal selection pressure. As early diagnostic tests for ...[more]

PMID: 25750739

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Project description:ObjectivesInfections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy.SettingThis systematic review included prospective randomised controlled trials and prospective single-arm studies.ParticipantsThe studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018.Primary and secondary outcome measuresPrimary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death.ResultsFrom 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking.ConclusionsOur results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review.Prospero registration numberCRD42017077606.

Project description:The propagation of epileptic seizure activity in the brain is a widespread pathophysiology that, in principle, should yield to intervention techniques guided by mathematical models of neuronal ensemble dynamics. During a seizure, neural activity will deviate from its current dynamical regime to one in which there are significant signal fluctuations. In silico treatments of neural activity are an important tool for the understanding of how the healthy brain can maintain stability, as well as of how pathology can lead to seizures. The hope is that, contained within the mathematical foundations of such treatments, there lie potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the dynamic causal modelling neuronal state equation generalises to a Fokker-Planck formalism if one extends the framework to model the ways in which activity propagates along the structural connections of neural systems. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity-i.e., by lowering the rate at which neuronal fluctuations disperse to neighbouring regions. We show, for neural systems prone to epileptic seizures, that such a reduction in diffusivity can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror the activity profile of a pathological region in its functionally connected areas. This counter-intuitive method is intended to be used pre-emptively-i.e., in order to mitigate the effects of the seizure, or ideally even prevent it from occurring in the first place. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network prior to seizure onset. Our hope is that this technique can form the basis for future real-time monitoring and intervention devices that are capable of treating epilepsy in a non-invasive manner.

Project description:BACKGROUND:Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). METHODS:Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. FINDINGS:In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup. INTERPRETATION:Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system.

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Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.

Publications

Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.

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