Clinical and microbiological features of candiduria in critically ill adult patients in Shiraz, Iran (2016–2018): deviations from international guidelines and fluconazole therapeutic failure

2020 ◽  
Author(s):  
Amir Arastehfar ◽  
Sara Khanjari ◽  
Zahra Zareshahrabadi ◽  
Wenjie Fang ◽  
Weihua Pan ◽  
...  
Keyword(s):  
Critically Ill ◽  
Antifungal Susceptibility ◽  
Standard Of Care ◽  
Therapeutic Failure ◽  
Antifungal Resistance ◽  
Adult Patients ◽  
High Rate ◽  
International Guidelines ◽  
Asymptomatic Patients ◽  
Standard Of Care Treatment

Abstract Candiduria is common among patients admitted to intensive care units (ICUs); however, clinical and microbiological data are limited, which accounts for non-compliance with international guidelines, including over treatment of asymptomatic candiduria that promotes antifungal resistance. This prospective study included adult patients admitted to ICUs of five referral hospitals in Shiraz, Iran, during 2016–2018. Species were identified by MALDI-TOF MS, and antifungal susceptibility was assessed according to CLSI M27-A3/S4. Among 2086 patients, 162 and 293 developed candiduria and bacteriuria, respectively. In total, 174 yeast isolates were collected; 88.5% were Candida albicans (91/174; 52.2%), C. glabrata (38/174; 21.8%), and C. tropicalis (25/174; 14.3%). Antifungal resistance was rare; only two isolates (one C. tropicalis and one C. krusei) were fluconazole resistant. Symptomatic candiduria was noted in 31.4% of patients (51/162); only 37% (19/51) of them were treated and 36.82% (7/19) showed fluconazole therapeutic failure. Two symptomatic patients developed candidemia shortly after candiduria. Among asymptomatic patients, 31.5% (35/111) were overtreated with fluconazole. The mortality rate was 25.3% (41/162); it did not differ between symptomatic and asymptomatic patients. Our results indicate that deviation from standard-of-care treatment for candiduria is a matter of concern given the high rate of fluconazole therapeutic failure among patients with symptomatic candiduria. Lay summary Candiduria is an underestimated clinical presentation among critically ill patients and detailed data are scarce in this regard. Given the high rate of fluconazole therapeutic failure and development of candidemia in some cases, the mistreatment of candiduria should not be overlooked by clinicians.

scholarly journals Expert Statements on the Standard of Care in Critically Ill Adult Patients With Atypical Hemolytic Uremic Syndrome

CHEST Journal ◽  
2017 ◽  
Vol 152 (2) ◽  
pp. 424-434 ◽  
Author(s):  
Elie Azoulay ◽  
Paul Knoebl ◽  
José Garnacho-Montero ◽  
Katerina Rusinova ◽  
Gennadii Galstian ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Critically Ill ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Standard Of Care ◽  
Adult Patients ◽  
Uremic Syndrome

Epidemiology of candidemia in Shiraz, southern Iran: A prospective multicenter study (2016–2018)

2020 ◽  
Author(s):  
Amir Arastehfar ◽  
Samira Yazdanpanah ◽  
Mina Bakhtiari ◽  
Wenjie Fang ◽  
Weihua Pan ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Species Identification ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Therapeutic Failure ◽  
Antifungal Resistance ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Treatment ◽  
Naive Patient ◽  
Southern Iran

Abstract Systematic candidemia studies, especially in southern Iran, are scarce. In the current prospective study, we investigated candidemia in three major healthcare centers of Shiraz, the largest city in southern Iran. Yeast isolates from blood and other sterile body fluids were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method. Clinical data were retrieved from patients’ medical records. In total, 113 yeast isolates were recovered from 109 patients, over 60% of whom received fluconazole. Antifungal drugs were prescribed without considering species identification or AFST. The all-cause mortality rate was 28%. Almost 30% of the patients were from intensive care units (ICUs). Candida albicans (56/113; 49.5%) was the most prevalent species followed by C. glabrata (26/113; 23%), C. parapsilosis (13/113; 11.5%), C. tropicalis (7/113; 6.2%), and C. dubliniensis (5/113; 4.4%). Only five isolates showed antifungal resistance or decreased susceptibility to fluconazole: one C. orthopsilosis isolate from an azole-naïve patient and two C. glabrata, one C. albicans, and one C. dubliniensis isolates from patients treated with azoles, who developed therapeutic failure against azoles later. Our results revealed a low level of antifungal resistance but a notable rate of azole therapeutic failure among patients with candidemia due to non-albicans Candida species, which threaten the efficacy of fluconazole, the most widely used antifungal in southern regions of Iran. Candidemia studies should not be confined to ICUs and treatment should be administered based on species identification and AFST results. Lay Abstract Landscape of candidemia is blurred in Iran, and only two studies from Tehran have extensively explored the epidemiology of candidemia. However, candidemia data from the other regions are notoriously scarce, which precludes from reaching a consensus regarding species distribution, the burden of antifungal resistance, and the clinical features of infected patients. Therefore, we conducted the current prospective candidemia study in Shiraz, one of the largest cities located in the south of Iran, from April 2016 to April 2018. More than 63% of the candidemia infections were treated by fluconazole and species identification and antifungal susceptibility testing were not used for decision making regarding the choice of antifungal treatment. Approximately 70% of the candidemia cases occurred in the wards outside of the ICUs. Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. dubliniensis were the five leading causative agents of candidemia. Antifungal resistance was rare and fluconazole resistance and/or non-wild type phenotypes were noticed in five isolates, only one was C. albicans and the rest were non-albicans Candida (NAC) species, including C. glabrata, C. dubliniensis, and C. orthopsilosis. Except for C. orthopsilosis, which was isolated from an azole-naïve patient, the rest of isolates were recovered from patients treated with azoles and all showed therapeutic failure to azoles. Collectively, our data will complete the candidemia picture in Iran and show that, although the level of resistance was rare, the therapeutic failure was notable among NAC species, which threatens the efficacy of fluconazole, the most widely used antifungal in Southern regions of Iran. Moreover, we showed that candidemia is poorly managed in Iran since species identification tools along with antifungal susceptibility testing were not used to select appropriate antifungal treatment.

Epidemiology and Antifungal Susceptibility in Patients with Candidemia in a University Hospital, Thailand

2020 ◽  
Vol 103 (10) ◽  
pp. 1048-1056
Keyword(s):  
Antifungal Susceptibility ◽  
Underlying Disease ◽  
Outcome Data ◽  
Adult Patients ◽  
Antifungal Treatment ◽  
University Hospital ◽  
Fluconazole Resistance ◽  
Fluconazole Therapy ◽  
Fluconazole Resistant ◽  
High Level

Background: Candidemia is the most common nosocomial invasive fungal infection that causes high mortality. Emergence of drug-resistant Candida is reported worldwide but there are few studies in Thailand. Objective: To determine the epidemiology, antifungal susceptibility of Candida, and outcomes among adult patients with candidemia. Materials and Methods: A prospective, observational study in adult patients with candidemia was conducted in 2015 at a university hospital. Demographic, microbiological, and outcome data were recorded. Results: Fifty-two patients with candidemia were identified, of whom 76.9% had an underlying disease and 69.2% had risks for candidemia. Sixty-four percent of candidemia patients contracted non-albicans Candida and 36% had Candida albicans. C. tropicalis was the most common non-albicans Candida species isolated (35%), followed by C. parapsilosis (19%), and C. glabrata (10%). Fluconazole resistance was found in 12.5% of C. albicans and in 11.1% of C. parapsilosis isolates. Reduced fluconazole susceptibility or high-level fluconazole resistance was found in 68.7% of C. tropicalis isolates. All except C. parapsilosis had excellent susceptibility to echinocandins. Seventy-three percent (38/52) of patients received antifungal treatment, of whom, 78.9% received empiric fluconazole therapy, and 89.7% were started on antifungal treatment 24 hours after the isolation of Candida. The overall mortality rate was 51.9%. Conclusion: Fluconazole-resistant Candida became more prevalent particularly in C. tropicalis, which was the predominant species among non-albicans Candida causing candidemia. Empiric treatment with either amphotericin B or echinocandins would be appropriate in high-risk patients with suspected candidemia. Trial registration: Thai Clinical Trials Registry, TCTR20150605001 Keywords: Candida, Fluconazole, Resistant, Thailand

scholarly journals Effect of gut microbiota modulation on feeding tolerance of enterally fed critically ill adult patients: a systematic review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Najmeh Seifi ◽  
Ali Jafarzadeh Esfahani ◽  
Alireza Sedaghat ◽  
Reza Rezvani ◽  
Majid Khadem-Rezaiyan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gut Microbiota ◽  
Beneficial Effect ◽  
Critically Ill ◽  
Energy Intake ◽  
Adult Patients ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Clinical Endpoints ◽  
Feeding Tolerance

Abstract Purpose The objective of this systematic review was to evaluate the effect of pre-, pro-, and synbiotics on feeding tolerance of enterally fed critically ill adult patients. Methods MEDLINE, Science Direct, Web of Knowledge, and the Cochrane Central Register of Controlled Trials were searched up to November 2019. English language randomized controlled trials reporting the effect of pre, pro or synbiotics on the feeding tolerance of enterally fed critically ill adult patients were included. Results Overall, 15 papers were selected for review. Among six studies reporting the energy intake, only two studies showed significantly higher energy intake in the prebiotic-receiving groups. Among four RCTs reporting frequency or time to achieve the target calorie, only one found a significant effect of probiotics to reduce the time to achieve a target dose of calorie. About the prevalence or duration of diarrhea, 7 out of 12 RCTs reported a beneficial effect. All but one study found no beneficial effects for gut microbiota manipulation on clinical endpoints including length of stay (LOS) in hospital and intensive care unit (ICU). Conclusion It should be noticed that the heterogeneity in study designs, product format, and ICU patient populations makes it difficult to draw any general conclusion. Overall, it seems that pre, pro, or synbiotics have no significant beneficial effect on feeding tolerance and clinical endpoints in critically ill adults, but they may reduce the prevalence or duration of diarrhea.

scholarly journals Caring for critically ill adults in paediatric intensive care units in England during the COVID-19 pandemic: planning, implementation and lessons for the future

2021 ◽  
pp. archdischild-2020-320962
Author(s):  
Ruchi Sinha ◽  
Angela Aramburo ◽  
Akash Deep ◽  
Emma-Jane Bould ◽  
Hannah L Buckley ◽  
...  
Keyword(s):  
Intensive Care ◽  
Intensive Care Units ◽  
Critically Ill ◽  
Clinical Care ◽  
Adult Patients ◽  
Paediatric Intensive Care ◽  
Critically Ill Adults ◽  
Care Capacity ◽  
Ill Adults ◽  
Paediatric Intensive Care Units

ObjectiveTo describe the experience of paediatric intensive care units (PICUs) in England that repurposed their units, equipment and staff to care for critically ill adults during the first wave of the COVID-19 pandemic.DesignDescriptive study.SettingSeven PICUs in England.Main outcome measures(1) Modelling using historical Paediatric Intensive Care Audit Network data; (2) space, staff, equipment, clinical care, communication and governance considerations during repurposing of PICUs; (3) characteristics, interventions and outcomes of adults cared for in repurposed PICUs.ResultsSeven English PICUs, accounting for 137 beds, repurposed their space, staff and equipment to admit critically ill adults. Neighbouring PICUs increased their bed capacity to maintain overall bed numbers for children, which was informed by historical data modelling (median 280–307 PICU beds were required in England from March to June). A total of 145 adult patients (median age 50–62 years) were cared for in repurposed PICUs (1553 bed-days). The vast majority of patients had COVID-19 (109/145, 75%); the majority required invasive ventilation (91/109, 85%). Nearly, a third of patients (42/145, 29%) underwent a tracheostomy. Renal replacement therapy was provided in 20/145 (14%) patients. Twenty adults died in PICU (14%).ConclusionIn a rapid and unprecedented effort during the first wave of the COVID-19 pandemic, seven PICUs in England were repurposed to care for adult patients. The success of this effort was underpinned by extensive local preparation, close collaboration with adult intensivists and careful national planning to safeguard paediatric critical care capacity.

scholarly journals TMOD-12. ESTABLISHING A CLINICALLY RELEVANT MODEL OF MESENCHYMAL GLIOBLASTOMA (GBM) TO STUDY RESPONSE TO STANDARD OF CARE TREATMENT AND IMMUNE CHECKPOINT INHIBITION (ICI).

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii230-ii230
Author(s):  
James Clerkin ◽  
Kate Connor ◽  
Kieron Sweeney ◽  
Kieron White ◽  
Liam Shiels ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Orthotopic Model ◽  
Aged Mice ◽  
Gl261 Cell ◽  
Standard Of Care Treatment ◽  
Clinical Models ◽  
Immune Contexture

Abstract GBM is a devastating disease with peak incidence in the seventh decade. Pre-clinical models are essential for studying resistance mechanisms and screening novel therapies. However, historically these models have failed to predict response in humans. Current models seldom incorporate surgical resection, and commonly use young animals whose immune contexture differs from older patients. Here, we have established an orthotopic model employing the syngeneic mesenchymal-NFpp10a-cell line which incorporates surgical resection in aged mice. We further characterise response to ICI and temozolomide monotherapy. NFpp10a and GL261-cell lines were exposed in vitro to irradiation (0Gy/2Gy/5Gy) and response assessed using colony formation assays. NFpp10a formed significantly more colonies at 5Gy compared to GL261 at both day 10 (NFpp10a 5.167 vs GL261 1.4; p=0.0017) and day 14 (NFpp10a 3.5 vs GL261 0; p< 0.0001). Hence, NFpp10a displays increased radioresistance. Next, NFpp10a-luciferin expressing cells were orthotopically implanted into young (6-8weeks;n=16) and aged (18months;n=16) C57BL/6-mice. Weekly bioluminescence imaging (BLI) was performed to monitor growth. Mice undergoing resection showed a median 18.47-fold drop in BLI signal. We demonstrated resection survival advantage in aged mice (Resection:33.5 days vs Non-Resection:18 days, p= 0.0166) and showed young age to be a positive prognostic factor (Young:62 days vs Aged:22 days, p=0.0002). Subsequently, we orthotopically implanted NFpp10a-Luc2 cells into C57BL/6 mice and treated with temozolomide (n=24) or PBS control (n=23), and anti-PD1 (n=24) or IgG (n=23). We observed that temozolomide and anti-PD1 monotherapy had no impact on NFpp10-Luc2 growth (temozolomide-overall:p=0.9001, anti-PD1-overall:p=0.7933) or survival (temozolomide-overall:p=0.3035, anti-PD1-overall:p=0.6328). Overall, we have established an NFpp10-Luc2 mesenchymal-GBM model in aged mice which incorporates surgical resection and accurately displays significant resistance to temozolomide and anti-PD1 monotherapy. We are currently employing this model to study the efficacy of neoadjuvant anti-PD1 therapy. Mechanistic analyses with multiplex-immunohistochemistry, scRNA and whole exome sequencing are planned to interrogate treatment effects on the tumor microenvironment.

scholarly journals Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 290
Author(s):  
Smarakan Sneha ◽  
Simon C. Baker ◽  
Andrew Green ◽  
Sarah Storr ◽  
Radhika Aiyappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Therapeutic Index ◽  
Cancer Cell Proliferation ◽  
Selective Treatment ◽  
Standard Of Care Treatment ◽  
Future Work ◽  
Treat Breast Cancer

Despite significant advances in treatment strategies over the past decade, selective treatment of breast cancer with limited side-effects still remains a great challenge. The cytochrome P450 (CYP) family of enzymes contribute to cancer cell proliferation, cell signaling and drug metabolism with implications for treatment outcomes. A clearer understanding of CYP expression is important in the pathogenesis of breast cancer as several isoforms play critical roles in metabolising steroid hormones and xenobiotics that contribute to the genesis of breast cancer. The purpose of this review is to provide an update on how the presence of CYPs impacts on standard of care (SoC) drugs used to treat breast cancer as well as discuss opportunities to exploit CYP expression for therapeutic intervention. Finally, we provide our thoughts on future work in CYP research with the aim of supporting ongoing efforts to develop drugs with improved therapeutic index for patient benefit.

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