scholarly journals Biomarker-guided antifungal stewardship policies for patients with invasive candidiasis

Author(s):  
Behnam Honarvar ◽  
Kamran Bagheri Lankarani ◽  
Mehdi Taghavi ◽  
Ghasem Vahedi ◽  
Esmaeil Mortaz

Invasive fungal infections (IFIs) are among the life-threatening issues in patients with impaired immune system. High administration of antifungals in these patients imposes a heavy economic burden on the national health system. In addition, despite the usually expensive antifungal regimens, the mortality rate due to fungal infections is still high, resulting in the loss of hundreds of lives per year.Survival rate is an indicator of the success of national healthcare policies. Early diagnosis of IFI is critical because any delays may be fatal. The weakness of the old-fashioned culture-based diagnostic methods lies in their time-consuming laboratory procedures. To overcome this problem, several diagnostic approaches have been developed to facilitate the early diagnosis of invasive candidiasis as the most prevalent IFI.These methods are based on the detection of serologic and molecular footprints. However, nowadays, antibiotic resistance and proper and cost-effective use of antibiotics are given special attention in national healthcare policies. The instructions for controlling these indices have been collected under the name of antibiotic stewardship. The present review study was targeted toward providing insight into novel diagnostic biomarkers and antifungal stewardship programs. The simultaneous investigation of these two issues facilitates the achievement of a novel health policy for the treatment of systemic candidiasis in immunocompromised patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Spampinato ◽  
Darío Leonardi

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.



2019 ◽  
Vol 31 (1) ◽  
pp. 65-71

Neonatal septicemia is a life-threatening yet treatable condition. It is one of the major health problems throughout the world. Blood culture is the gold standard for diagnosis of neonatal septicemia and should be performed in all cases of suspected septicemia prior to starting antibiotics. But in the present study, the use of the haematological parameters was evaluated to determine the early diagnosis of neonatal septicemia. It was carried out in the neonatal unit of Mandalay Children’s Hospital from September 2012 to August 2013. Out of 68 cases of clinically suspected neonatal septicemia, bacterial pathogens were isolated from 33 cases. Early onset neonatal septicemia was more common than late onset. Among 33 cases of culture-proven neonatal septicemia, septicemia is not likely in 1 case (3%) while borderline for septicemia and septicemia in 6 cases (18.2%) is very likely in 26 cases (78.8%) according to haematological scoring system (HSS). HSS assigns a score of one for each of seven haematological parameters. Out of the seven haematological parameters, immature to total neutrophil ratio (I:T) and immature to mature neutrophil ratio (I:M) were the most reliable test for the neonatal septicemia. Thrombocytopenia had low sensitivity. The haematolgical parameters are simple, quick, cost effective and readily available. The sensitivity, specificity and the predictive values of haematological parameters could be enhanced by combination of these parameters rather than the use of single parameter.



Author(s):  
Amelie P. Brackin ◽  
Sam J. Hemmings ◽  
Matthew C. Fisher ◽  
Johanna Rhodes

AbstractRespiratory infections caused by fungal pathogens present a growing global health concern and are a major cause of death in immunocompromised patients. Worryingly, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome has been shown to predispose some patients to airborne fungal co-infections. These include secondary pulmonary aspergillosis and mucormycosis. Aspergillosis is most commonly caused by the fungal pathogen Aspergillus fumigatus and primarily treated using the triazole drug group, however in recent years, this fungus has been rapidly gaining resistance against these antifungals. This is of serious clinical concern as multi-azole resistant forms of aspergillosis have a higher risk of mortality when compared against azole-susceptible infections. With the increasing numbers of COVID-19 and other classes of immunocompromised patients, early diagnosis of fungal infections is critical to ensuring patient survival. However, time-limited diagnosis is difficult to achieve with current culture-based methods. Advances within fungal genomics have enabled molecular diagnostic methods to become a fast, reproducible, and cost-effective alternative for diagnosis of respiratory fungal pathogens and detection of antifungal resistance. Here, we describe what techniques are currently available within molecular diagnostics, how they work and when they have been used.



Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 29 ◽  
Author(s):  
Faustino ◽  
Pinheiro

Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials.



Author(s):  
Sony Paul ◽  
Iyanar Kannan

Background and Purpose: Opportunistic fungal infections have been on a growingtrend since the last two decades. Among the opportunistic fungal agents, Candidaspecies, Cryptococcus neoformans, and Aspergillus fumigatus account for most of thelife-threatening infections in immunocompromised individuals. Regarding this, thepresent study aimed to investigate the molecular identification and antifungalsusceptibility pattern of Candida species isolated from HIV-infected patients.Materials and Methods: This study was conducted on 80 clinical samples collectedfrom HIV-infected patients with suspected candidiasis referring to Tagore MedicalCollege and Hospital, Rathinamangalam and Government Hospital of ThoracicMedicine, in Chennai, India, for 18 months (i.e., May 2016-December 2017). Phenotypicand molecular identification was accomplished using internal transcribed spacer region 1(ITS1) and ITS4 primers. The antifungal susceptibility pattern of the isolates against fourantifungal agents was also determined by both disk diffusion and broth dilution methods.Results: In the present study, the prevalence of candidiasis was obtained as 75% (n=60).Candida tropicalis was the predominant identified species. All the emerging species(i.e., Kodamaea ohmeri, Hanseniaspora opuntiae, and C. orthopsilosis) were identifiedthrough molecular identification since the phenotypic identification was inconclusive. Interms of the susceptibility pattern, 63.3% and 18.3% of the isolates were resistant tofluconazole and voriconazole, respectively. Candida albicans was also found to beresistant to amphotericin B.Conclusion: Molecular assay led to the identification of K. ohmeri, H. opuntiae, and C.orthopsilosis, which were multidrug-resistant. This study highlighted the need for theprompt and timely identification of clinical yeast isolates given the emergence of manyrare species and their capability of causing life-threatening infections and outbreaks. Inthe laboratories where molecular diagnostic methods are not available, alternativeservices of reference laboratories can be utilized as cost-effective measures. With regardto the growing prevalence of antifungal drug resistance, antifungal susceptibility testingshould be made mandatory for effective patient management.



2019 ◽  
Vol 9 (4) ◽  
pp. 11-20
Author(s):  
B. Z. Belotserkovskiy ◽  
E. B. Gelfand ◽  
A. O. Bykov ◽  
O. A. Mamontova ◽  
D. N. Protsenko

This review focuses on the practical aspects of prevention and treatment of fungal infections in surgical patients. It covers epidemiology and risk factors for invasive candidiasis, updates on the etiological structure of fungal infections in patients in critical conditions, and provides the information on drug sensitivity of Candida species. The authors discuss the limitations of cultural and non-cultural diagnostic methods used in invasive candidiasis, emphasizing the importance of analyzing the existing risk factors in combination with a comprehensive assessment of clinical and laboratory data for timely initiation of adequate antifungal therapy. The review provides a brief description of currently available antimicotics, including polyenes, triazoles, and echinocandins. It also describes the benefits of anidulafungin, which does not interact with other drugs and has no negative effect on the liver and kidney. The article also covers indications for antifungal agents in surgical intensive care units in accordance with international and Russian guidelines. A cohort of patients with abdominal diseases requiring preventive and empirical treatment with antimicotics is described. In additions to that, the manuscript contains a rationale for the use of echinocandins in targeted therapy of invasive candidiasis.



2021 ◽  
Vol 7 (1) ◽  
pp. 59
Author(s):  
Marina Machado ◽  
Esther Chamorro de Vega ◽  
María del Carmen Martínez-Jiménez ◽  
Carmen Guadalupe Rodríguez-González ◽  
Antonio Vena ◽  
...  

The implementation of 1,3 β-d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre–post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%; p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29; p < 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%; p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 €/patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.



2019 ◽  
Vol 141 (3-4) ◽  
pp. 97-105

Invasive fungal infections (IFI) are an important problem of modern medicine. The reason is growing population of immunocompromised patients and high morbidity and mortality of these infections. Timely diagnosed IFI is of utmost importance because the delay of antifungal treatment has impact on treatment outcome. Cultivation as a conventional diagnostic method has low sensitivity, long duration and demands obtaining invasive samples. Therefore, in the last two decades fungal biomarkers are investigated for earlier and more sensitive diagnostics. 1,3-β-D-glucan (BDG) is a fungal biomarker in patients’ sera that enables detection of the following fungal pathogens: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporotrix schenckii, Saccharomyces cerevisiae and Pneumocystis jirovecii. Low level and absence of BDG in the cell wall unables the detection of Cryptococcus spp. and order Mucorales with this test. High negative predictive value of BDG can be used when deciding to stop antifungal treatment and be a part of strategy for antifungal stewardship in intensive care units. In hematological patients BDG can be used as a screening method or as a part of diagnostic work-up when IFI is suspected. Reliability of test result is higher when two or more consecutive samples are positive. Influence of antifungal prophylaxis on BDG test results is still unclear. BDG kinetics and its relation to clinical outcome are still investigated. For pediatric population cut-off values for interpretation are still not defined, although many studies have been published investigating this issue. Although still not recommended by pediatric guidelines, this test can help in certain situations having in mind its limitations. BDG as a fungal marker represents the significant progress in IFI diagnostics. With simultaneous application of other diagnostic methods, exact interpretation and rational use, it can help earlier and more successful diagnostics and treatment of IFI.



2017 ◽  
Vol 68 (11) ◽  
pp. 2566-2569 ◽  
Author(s):  
Elena Rusu ◽  
Ionela Sarbu ◽  
Magdalena Mitache ◽  
Horatiu Moldovan ◽  
Carmen Ioana Biris ◽  
...  

The high frequency of occurrence of candidiasis as well as high mortality of patients with immunosuppression cause a tendency toward better understanding of Candida albicans species virulence factors and developing sensitive and specific diagnostic methods, and appropriate strategies of candidiasis treatment. In recent decades the incidence of fungal infections has alarming increases because of advanced medical treatments. In this study was analyzed possible ultrastructural changes of the species C. albicans cells following treatment with sodium diclofenac at various concentrations. Following treatment of C. albicans cells with sodium diclofenac 1 mM and 2 mM changes in the plasmalemma can be noticed, changes in the density of cell wall, disruption and necrotic appearance of the cytoplasm.



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