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      Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

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          Abstract

          Background

          Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians.

          Main body

          This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed.

          Conclusion

          There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.

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          Most cited references101

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          Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

          It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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            Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

            ABSTRACT Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.
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              Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016

              Abstract Background The emergence of antifungal resistance threatens effective treatment of invasive fungal infection (IFI). Invasive candidiasis is the most common health care–associated IFI. We evaluated the activity of fluconazole (FLU) against 20 788 invasive isolates of Candida (37 species) collected from 135 medical centers in 39 countries (1997–2016). The activity of anidulafungin, caspofungin, and micafungin (MCF) was evaluated against 15 308 isolates worldwide (2006–2016). Methods Species identification was accomplished using phenotypic (1997–2001), genotypic, and proteomic methods (2006–2016). All isolates were tested using reference methods and clinical breakpoints published in the Clinical and Laboratory Standards Institute documents. Results A decrease in the isolation of Candida albicans and an increase in the isolation of Candida glabrata and Candida parapsilosis were observed over time. Candida glabrata was the most common non–C. albicans species detected in all geographic regions except for Latin America, where C. parapsilosis and Candida tropicalis were more common. Six Candida auris isolates were detected: 1 each in 2009, 2013, 2014, and 2015 and 2 in 2016; all were from nosocomial bloodstream infections and were FLU-resistant (R). The highest rates of FLU-R isolates were seen in C. glabrata from North America (NA; 10.6%) and in C. tropicalis from the Asia-Pacific region (9.2%). A steady increase in isolation of C. glabrata and resistance to FLU was detected over 20 years in the United States. Echinocandin-R (EC-R) ranged from 3.5% for C. glabrata to 0.1% for C. albicans and C. parapsilosis. Resistance to MCF was highest among C. glabrata (2.8%) and C. tropicalis (1.3%) from NA. Mutations on FKS hot spot (HS) regions were detected among 70 EC-R isolates (51/70 were C. glabrata). Most isolates harboring FKS HS mutations were resistant to 2 or more ECs. Conclusions EC-R and FLU-R remain uncommon among contemporary Candida isolates; however, a slow and steady emergence of resistance to both antifungal classes was observed in C. glabrata and C. tropicalis isolates.
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                Author and article information

                Contributors
                emilio.maseda@gmail.com
                drmartinloeches@gmail.com
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                3 October 2023
                3 October 2023
                2023
                : 27
                : 382
                Affiliations
                [1 ]Service of Anesthesia, Hospital Quirónsalud Valle del Henares, Av. de La Constitución, 249, 28850 Torrejón de Ardoz, Madrid, Spain
                [2 ]Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James’s Hospital, ( https://ror.org/04c6bry31) James Street, Leinster, Dublin 8, D08 NHY1 Ireland
                [3 ]GRID grid.5841.8, ISNI 0000 0004 1937 0247, Pulmonary Intensive Care Unit, Respiratory Institute, Hospital Clinic of Barcelona, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi I Sunyer), , University of Barcelona, CIBERes, ; Barcelona, Spain
                [4 ]ICU, Hospital Universitario Dr. Peset, ( https://ror.org/03971n288) Valencia, Spain
                [5 ]Microbiology Department, Hospital Universitari I Politecnic La Fe, ( https://ror.org/01ar2v535) Valencia, Spain
                [6 ]Infectious Diseases Service, Hospital Universitario Ramón y Cajal, ( https://ror.org/050eq1942) Madrid, Spain
                [7 ]Service of Pharmacy, Hospital del Mar, ( https://ror.org/03a8gac78) Barcelona, Spain
                [8 ]Service of Anesthesia, Hospital Clínico Universitario de Valencia, ( https://ror.org/00hpnj894) Valencia, Spain
                [9 ]Service of Anesthesia, Área Sanitaria de Pontevedra, Pontevedra, Spain
                [10 ]GRID grid.413457.0, ISNI 0000 0004 1767 6285, ICU, Hospital Universitario Son Llátzer, ; Palma, Spain
                [11 ]Faculty of Sports Sciences and Physiotherapy, Universidad Europea de Madrid, ( https://ror.org/04dp46240) Madrid, Spain
                [12 ]ICU, Hospital Universitario de Tarragona Juan XXIII, ( https://ror.org/05s4b1t72) Tarragona, Spain
                [13 ]Fundación Micellium, La Eliana, Valencia, Spain
                Article
                4673
                10.1186/s13054-023-04673-6
                10546659
                37789338
                72ae50b7-2da4-4e43-8ee1-e3bbd7e0f64f
                © BioMed Central Ltd., part of Springer Nature 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 August 2023
                : 28 September 2023
                Categories
                Perspective
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Emergency medicine & Trauma
                intraabdominal candidiasis,echinocandins,liposomal amphotericin b,pk/pd,guidelines,decision algorithm,intraabdominal penetration,antifungal stewardship

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