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1.
Mikrobiyol Bul ; 55(4): 568-579, 2021 Oct.
Artigo em Turco | MEDLINE | ID: mdl-34666656

RESUMO

Candida species are responsible for 70-90% of invasive fungal infections in the intensive care unit. Early diagnosis and treatment is important in candidemia. Improper diagnosis and treatment increases mortality and morbidity significantly. Because of the late results of blood cultures and low sensitivity of the serological tests when used alone, molecular methods should be investigated in this field. In this study, the results of the Candida real-time polymerase chain reaction (Rt-PCR) test, which was studied from blood culture and whole blood, were compared in patients with high candidemia risk who were followed in the General Surgery Intensive Care and Anesthesiology and Reanimation Unit of Cukurova University Faculty of Medicine. It was aimed to investigate the practical utility of Candida RT-PCR test, which is a rapid diagnosis method in patients with suspected candidemia. In our study, 90 patients with high risk of candidemia according to the criteria determined according to the guidelines were evaluated prospectively. Urine, perineum, axilla, tracheal aspirate culture and two sets of blood cultures were obtained from the patients. Blood sample was also drawn into an ethylenediaminetetraacetic acid (EDTA) tube and stored at -40°C for later Candida Rt-PCR study. In Candida Rt- PCR, species-specific primers were used to distinguish species. Candida score (CS) of the patients was calculated. Forty one (45.5%) of the patients were female and 49 (55.5%) were male. The median age of the patients was 61.5 years. Candida was positive in blood culture in three (3.3%) of the patients included in the study, while Candida Rt-PCR was positive in 17 (18.9%). Candida species detected in the blood culture and Rt-PCR test were compatible with each other. Rt-PCR was significantly more positive (p= 0.006). Candida Rt-PCR positivity was significantly higher in patients receiving total parenteral nutrition (p= 0.028), malignancy (p= 0.021), and history of surgery in the last three months (p=0.003). The difference in CS between patients with PCR positive and PCR negative was statistically significant (p= 0.015). Our study was conducted in a high-risk population for candidemia and the results of Candida Rt-PCR was found to be more positive than blood culture. Rt-PCR positivity and blood culture positivity were associated with high CS. In the light of these data, it was thought that it would be appropriate to use molecular methods in the diagnosis and support them with CS, especially in patients with high risk of candidemia. Considering that blood culture, which is the gold standard for the diagnosis of candidemia, gives late results and is 50% positive, using faster diagnostic methods for candidemia is important to reduce mortality and morbidity. The fast and good results of Candida PCR method have shown that it can be used in diagnosis. However, lack of standardization of primers used in PCR tests may cause false positives. Additional studies are needed in this respect.


Assuntos
Hemocultura , Candidemia , Candida/genética , Candidemia/diagnóstico , Candidemia/epidemiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
2.
Mikrobiyol Bul ; 55(4): 648-655, 2021 Oct.
Artigo em Turco | MEDLINE | ID: mdl-34666664

RESUMO

Candida auris is a species of fungus that has gained importance in recent years owing to its ability to cause hospital infections and epidemics, resistant to antifungal agents and disinfection processes and frequently misidentified by commercial systems. Hospital outbreaks caused by C.auris have been reported from some countries. It has been determined that C.auris has lower virulence than Candida albicans; however, it is associated with high mortality rates in immunocompromised individuals. An increase in the incidence of invasive fungal infections which can lead to serious complications and death, has been identified in severe coronavirus-2019 (COVID-19) patients or immunocompromised individuals with underlying disease. Studies demonstrated an increase in the frequency of C.auris isolation in COVID-19 patients with candidemia. In this report, the first case of COVID-19 positive C.auris fungemia detected in Turkey was presented. A 71-year-old male patient with a history of myocardial infarction, diabetes mellitus, donation of a single kidney and lobectomy surgery due to lung cancer was hospitalized in the pandemic thoracic surgery service due to the findings consistent with viral pneumonia on thoracic computed tomography. Favipiravir 2 x 600 mg and intravenous dexamethasone 1 x 6 mg therapy was administered. The patient tested positive for SARS-CoV-2 polymerase chain reaction, and severe involvement of the left lung was detected in the following days. Antibiotics were administered, followed by insertion of a right jugular vein catheter and initation of tocilizumab. The patient was transferred to the intensive care unit due to increased respiratory distress. Yeast growth was detected in the patient's hemoculture. The yeast strain could not be identified using API ID 32C (bioMerieux, France) (Sacchromyces kluyveri, Candida sake, unacceptable profile), but was identified as C.auris using the VITEK MALDI TOF MS (bioMerieux, France) (99.9%) system and confirmed by sequencing. The minimum inhibitor concentration values were detected as 3 µg/ml for amphotericin B; > 256 µg/ml for fluconazole; 0.19 µg/ml for voriconazole; 0.19 µg/ml for itraconazole; 0.016 µg/ml for posaconazole; 1 µg/ml for caspofungin and 0.094 µg/ml for anidulafungin by using the antibiotic gradient method. The patient's initial treatment comprised meropenem 3 x 1 g, vancomycin 2 x 1 g, caspofungin 1 x 70 mg, and continued as caspofungine 1 x 50 mg after the loading dose, and vancomycin 1 x 1 g/48 hours from the third day of treatment. The patient died on the ninth day after developing candidemia. The present case is the first case of fungemia caused by C.auris in a COVID-19 positive patient in Turkey, and it emphasizes the need of caution for fungemia due to C.auris in intensive care units in our country which has a high COVID-19 incidence.


Assuntos
COVID-19 , Candidemia , Fungemia , Idoso , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidemia/diagnóstico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Fungemia/tratamento farmacológico , Humanos , Masculino , Testes de Sensibilidade Microbiana , SARS-CoV-2 , Turquia/epidemiologia
3.
Front Immunol ; 12: 662171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512620

RESUMO

Circulatory inflammatory proteins play a significant role in anti-Candida host immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response to C. albicans. To systematically characterize inflammatory responses in Candida infection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans yeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort. To identify the genetic factors that determine variation in inflammatory protein responses, we correlated genome-wide single nucleotide polymorphism (SNP) genotypes with protein abundance (protein quantitative trait loci, pQTLs) produced by the Candida-stimulated PBMCs. Furthermore, we investigated whether differences in survival of candidaemia patients can be explained by modulating levels of inflammatory proteins. We identified five genome-wide significant pQTLs that modulate IL-8, MCP-2, MMP-1, and CCL3 in response to C. albicans. In addition, our genetic analysis suggested that GADD45G from rs10114707 locus that reached genome-wide significance could be a potential core gene that regulates a cytokine network upon Candida infection. Last but not least, we observed that a trans-pQTL marked from SNP rs7651677 at chromosome 3 that influences urokinase plasminogen activator (uPA) is strongly associated with patient survival (P survival = 3.52 x 10-5, OR 3). Overall, our genetic analysis showed that genetic variation determines the abundance of circulatory proteins in response to Candida infection.


Assuntos
Candidemia/genética , Candidemia/imunologia , Variação Genética , Genótipo , Inflamação/genética , Inflamação/microbiologia , Proteínas/análise , Locos de Características Quantitativas/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Citocinas/imunologia , Feminino , Humanos , Inflamação/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteômica , Adulto Jovem
4.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472809

RESUMO

INTRODUCTION: Candidemia is the fourth common cause of blood stream infection worldwide leading to increased mortality and morbidity. A paradigm shift of Candida albicans to Non-albicans candida (NAC) had led to the increase in resistance to empirically used antifungals. So, an epidemiological study and antifungal susceptibility is essential for meticulous use of antifungals. AIMS AND OBJECTIVES: To find out the prevalence and antifungal susceptibility of Candida species causing candidemia. METHODS: automated blood culture done in BACTEC system followed by its identification and susceptibility testing in VITEK-2 system. RESULTS: Non-albicans candida was isolated from 73% cases of candidemia. The commonest isolate among neonates and adults were C.krusei and C.tropicalis respectively. C.haemulonii was significantly high among adult population while C.krusei was significantly high among the neonates. 10.4% NAC isolates were resistant to amphotericin B, flucytosine resistance among 37% NAC isolates and among 44% C.albicans isolates, fluconazole resistance was found among 13% and 15% of NAC and C. albicans respectively. Echinocandins were comparatively sensitive to the candida spp.


Assuntos
Candida , Candidemia , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Fluconazol/farmacologia , Humanos , Índia/epidemiologia , Recém-Nascido , Testes de Sensibilidade Microbiana
5.
Front Public Health ; 9: 631865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458217

RESUMO

Catheter-related bloodstream infection (CRBSI) is an important healthcare-associated infection caused by various nosocomial pathogens. Candida parapsilosis has emerged as a crucial causative agent for the CRBSI in the last two decades. Many factors have been associated with the development of CRBSI including, demography, pre-maturity, comorbidities (diabetes mellitus, hypertension, heart diseases, neuropathy, respiratory diseases, renal dysfunction, hematological and solid organ malignancies, and intestinal dysfunction), intensive care unit (ICU) admission, mechanical ventilation (MV), total parenteral nutrition (TPN), prior antibiotic and/or antifungal therapy, neutropenia, prior surgery, immunosuppressant, and type, site, number, and duration of catheters. This study aims to determine C. parapsilosis CRBSI risk factors. A retrospective study has been performed in an 853-bedded tertiary-care hospital in north-eastern Malaysia. All inpatients with C. parapsilosis positive blood cultures from January 2006 to December 2018 were included, and their medical records were reviewed using a standardized checklist. Out of 208 candidemia episodes, 177 had at least one catheter during admission, and 31 cases had not been catheterized and were excluded. Among the 177 cases, 30 CRBSI cases were compared to 147 non-CRBSI cases [81 bloodstream infections (BSIs), 66 catheter colonizers]. The significance of different risk factors was calculated using multivariate analysis. Multivariate analysis of potential risk factors shows that ICU admission was significantly associated with non-CRBSI as compared to CRBSI [OR, 0.242; 95% CI (0.080-0.734); p = 0.012], and TPN was significantly positively associated with CRBSI than non-CRBSI [OR, 3.079; 95%CI (1.125-8.429); p = 0.029], while other risk factors were not associated significantly. Patients admitted in ICU were less likely to develop C. parapsilosis CRBSI while patients receiving TPN were more likely to have C. parapsilosis CRBSI when compared to the non-CRBSI group.


Assuntos
Candida parapsilosis , Candidemia , Candidemia/epidemiologia , Cateteres , Humanos , Estudos Retrospectivos , Fatores de Risco
6.
Antimicrob Agents Chemother ; 65(9): e0051721, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34228535

RESUMO

Candida auris is a multidrug-resistant fungal pathogen that is endemic in South African hospitals. We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidemia in 2016 and 2017. We confirmed the species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using broth microdilution and Etest methods. We interpreted MICs using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared them to the C. auris B8441 reference strain. Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (94%) to fluconazole alone (MICs of ≥32 µg/ml), 19 (6%) to fluconazole and amphotericin B (MICs of ≥2 µg/ml), and 1 (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (resistant to fluconazole, amphotericin B, and echinocandins). Of 92 isolates selected for whole-genome sequencing, 77 clustered in clade III, including the pan-resistant isolates, 13 in clade I, and 2 in clade IV. Eighty-four of the isolates (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, and E343D in ERG11; N647T in MRR1; A651P, A657V, and S195G in TAC1b; S639P in FKS1HP1; and S58T in ERG3. Most South African C. auris isolates were resistant to azoles, although resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically susceptible isolates.


Assuntos
Antifúngicos , Candidemia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/genética , Candidemia/tratamento farmacológico , Farmacorresistência Fúngica/genética , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , África do Sul
7.
J Infect Chemother ; 27(11): 1562-1570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34217605

RESUMO

BACKGROUND: Current guidelines recommend echinocandins for the initial treatment of candidemia. However, polyenes are often chosen in clinical settings because of their fungicidal and anti-biofilm effects. Therefore, we performed a systematic review and meta-analysis to evaluate whether echinocandins are superior to polyenes in terms of mortality for the initial treatment of candidemia. METHODS: We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL databases until July 1, 2020. We compared the mortality rates of patients who received echinocandins and polyenes. As a subgroup analysis, we compared the mortality rates following the use of echinocandins versus liposomal amphotericin B. RESULTS: Fifteen studies involving 854 patients were included. Various Candida species were detected, and the rates of resistance of echinocandins and polyenes against the overall detected isolates were 1.0% and 0%, respectively. The overall mortality recorded in 15 studies was 41.0%, and the mortality was significantly higher for polyenes than echinocandins (odd ratios [OR] 1.68, 95% confidential interval [CI] 1.17-2.42). Furthermore, liposomal amphotericin B showed higher mortality in the initial treatment than echinocandins (OR 1.42; 95% CI 0.84-2.39). CONCLUSIONS: We revealed an association between echinocandin treatment and reduced mortality in the initial treatment of candidemia when causative fungi were not considered. Our findings partially support current guidelines recommending echinocandins for the treatment of candidemia.


Assuntos
Candidemia , Equinocandinas , Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Equinocandinas/uso terapêutico , Fluconazol , Humanos , Polienos/uso terapêutico
9.
Mycoses ; 64(8): 817-822, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091966

RESUMO

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.


Assuntos
Corticosteroides/administração & dosagem , Antifúngicos/administração & dosagem , Basidiomycota/isolamento & purificação , COVID-19/complicações , Superinfecção/complicações , Tricosporonose/complicações , Corticosteroides/farmacologia , Idoso , Antifúngicos/farmacologia , Basidiomycota/classificação , Basidiomycota/efeitos dos fármacos , Basidiomycota/genética , Brasil/epidemiologia , COVID-19/epidemiologia , Candidemia/complicações , Feminino , Fungemia/complicações , Haplótipos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Filogenia , Fatores de Risco , Superinfecção/epidemiologia , Tricosporonose/epidemiologia
10.
Mycoses ; 64(9): 1083-1091, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34085319

RESUMO

Severe COVID-19 patients in ICU are at high risk for candidemia due to exposure to multiple risk factors for candidemia. We aimed to compare the incidence of candidemia in ICU patients with and without COVID-19, and to investigate epidemiologic and clinical characteristics of candidemia patients and risk factors for mortality in candidemia patients. This retrospective study was conducted in patients followed in the ICUs of Ankara City Hospital for 2 years, divided into pre-pandemic and pandemic periods. The incidence (event per 1000 patient-days) and epidemiology of candidemia, clinical and laboratory characteristics of patients were compared in COVID-19 and non-COVID-19 groups. Candidemia incidence was higher in the COVID-19 group (2.16, 95% CI 1.77-2.60) than the non-COVID-19 group (1.06, 95% CI 0.89-0.125) (p < .001). A total of 236 candidemia episodes (105 in COVID-19 patients and 131 in non-COVID-19 patients) were detected during the study periods. COVID-19 cases had a higher rate of corticosteroid use (63.8% vs. 9.9%, p < .001). Epidemiology of candidemia and antifungal susceptibility were similar. Candidemia developed 2 weeks earlier in COVID-19 groups and resulted in higher mortality (92.5% vs. 79.4%, p .005). One-third of candidemia patients died before receiving any antifungal treatment, and this rate was higher in the COVID-19 group. In multivariate logistic regression analysis, corticosteroid use, presence of sepsis and age older than 65 years were independent risk factors for mortality in candidemia patients. Candidemia with high mortality is a more serious problem for COVID-19 patients due to its increased incidence, earlier occurrence and a higher rate of mortality.


Assuntos
Antifúngicos/uso terapêutico , COVID-19/complicações , COVID-19/microbiologia , Candidemia/tratamento farmacológico , Candidemia/mortalidade , Candidemia/fisiopatologia , Mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Candidemia/diagnóstico , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Turquia/epidemiologia
11.
J Mycol Med ; 31(3): 101168, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34186378

RESUMO

INTRODUCTION: Critically ill COVID-19 patients are at high risk for nosocomial bacterial and fungal infections due to several predisposing factors such as intensive care unit stay, mechanical ventilation, and broad-spectrum antibiotics. Data regarding multidrug resistant (MDR) Candida species in COVID-19 patients is scarce, and nonexistent regarding Candida duobushaemulonii superinfections. CASE DESCRIPTION: A 34-year-old male presented to our institution with acute respiratory distress syndrome (ARDS) due to COVID-19 infection and developed Candida duobushaemulonii fungemia after multiple courses of antibiotics and prolonged mechanical ventilation. He died after recurrent pneumothorax led to respiratory failure and cardiac arrest. DISCUSSION: Bacterial and fungal infections are common complications of viral pneumonia in critically ill patients. Data regarding these infections in COVID-19 patients has been poorly studied with only a few cases reporting secondary infection, mostly without identifying specific pathogens. Prolonged hospital stays, invasive interventions (central venous catheter, mechanical ventilation), and the use of broad-spectrum antibiotics in COVID-19 infections could carry a high risk of bacterial and/or fungal superinfections. CONCLUSION: Strategies to improve outcome in COVID-19 ICU patients should include early recognition of candidemia and appropriate antifungal therapy.


Assuntos
COVID-19/complicações , Candidemia/tratamento farmacológico , Superinfecção/tratamento farmacológico , Adulto , Antifúngicos/uso terapêutico , Candida , Candidemia/complicações , Evolução Fatal , Humanos , Masculino , Respiração Artificial , Síndrome do Desconforto Respiratório , Saccharomycetales , Superinfecção/complicações
12.
Stud Health Technol Inform ; 281: 1081-1082, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042847

RESUMO

Invasive candidiasis is associated with high morbidity and mortality in critically ill patients, i.e. patients admitted to Intensive Care Units (ICUs) or in surgical wards. There are no clinical signs or specific symptoms and even though early diagnosis risk scores and rapid tests are available, none of such strategies has an equally-optimal level of sensitivity and specificity. In the era of Electronic Health Records (EHRs), several clinical studies exploited Machine Learning (ML) models and large database of features to improve the diagnosis accuracy. The main aim of this work is to build a wide dataset which can be exploited to apply ML models to further improve the early recognition of candidemia at the bedside of patients with compatible signs and symptoms.


Assuntos
Candidemia , Candidíase , Candidemia/diagnóstico , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Fatores de Risco
13.
Front Cell Infect Microbiol ; 11: 676177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968809

RESUMO

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019-2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019-2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.


Assuntos
Candida parapsilosis , Candidemia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida parapsilosis/genética , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Criança , Surtos de Doenças , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Turquia/epidemiologia
14.
Emerg Infect Dis ; 27(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34014153

RESUMO

We determined the effect of HIV infection on deaths among persons >18 months of age with culture-confirmed candidemia at 29 sentinel hospitals in South Africa during 2012-2017. Of 1,040 case-patients with documented HIV status and in-hospital survival data, 426 (41%) were HIV-seropositive. The in-hospital case-fatality rate was 54% (228/426) for HIV-seropositive participants and 37% (230/614) for HIV-seronegative participants (crude odds ratio [OR] 1.92, 95% CI 1.50-2.47; p<0.001). After adjusting for relevant confounders (n = 907), mortality rates were 1.89 (95% CI 1.38-2.60) times higher among HIV-seropositive participants than HIV-seronegative participants (p<0.001). Compared with HIV-seronegative persons, the stratum-specific adjusted mortality OR was higher among HIV-seropositive persons not managed in intensive care units (OR 2.27, 95% CI 1.47-3.52; p<0.001) than among persons who were (OR 1.56, 95% CI 1.00-2.43; p = 0.05). Outcomes among HIV-seropositive persons with candidemia might be improved with intensive care.


Assuntos
Candidemia , Infecções por HIV , Humanos , Fatores de Risco , África do Sul
15.
Microb Pathog ; 155: 104889, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33878395

RESUMO

BACKGROUND: Biofilm formation by Candida species is an influential virulence factor in candidemia pathogenesis. We investigated the relationship between biofilm formation of Candida tropicalis isolates with the clinical characteristics and mortality outcomes in patients with candidemia. MATERIALS AND METHODS: Thirty-nine C. tropicalis isolates were recovered from patients with candidemia admitted to two university hospitals in Tehran, Iran. Biofilm mass and metabolic activity of C. tropicalis biofilms were assessed in vitro with two colorimetric methods. The sessile minimum inhibitory concentrations (SMICs) were evaluated in vitro by treating preformed biofilms with diluted concentrations of azoles according to CLSI-M27 A3/S4 protocol, followed by metabolic activity quantification. The expressions of ERG11, UPC2, MDR1, and CDR1 genes were also evaluated. RESULTS: All C. tropicalis isolates produced biofilm. Respectively, higher <7-day and ≥7-day mortality rates were found among cases with high metabolic activity (46.7% vs. 13%, P = 0.03) and high biofilm mass (31.8% vs. 0, P = 0.029). Sessile cells had high resistance to fluconazole, voriconazole, and itraconazole. The azole minimum inhibitory concentrations (MICs) of C. tropicalis sessile were significantly greater than the planktonic minimum inhibitory concentrations (PMICs). In fluconazole-treated biofilms, the expression of ERG11 and UPC2 genes was increased. CONCLUSION: Our findings highlight the importance of C. tropicalis biofilm formation as an important factor in candidemia pathogenesis and the clinical outcome of patients with candidemia.


Assuntos
Candida tropicalis , Candidemia , Antifúngicos/farmacologia , Biofilmes , Candida tropicalis/genética , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Irã (Geográfico) , Testes de Sensibilidade Microbiana
16.
Clin Drug Investig ; 41(6): 539-548, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33891293

RESUMO

BACKGROUND: Solid tumors are a common predisposing factor for invasive candidiasis (IC) or candidemia due to IC. OBJECTIVES: Post hoc analysis of patient-level efficacy and safety data from six studies of anidulafungin (with similar protocols/endpoints) in adults with IC/candidemia summarized by past or recent diagnosis of solid tumors. PATIENTS/METHODS: Patients received a single intravenous (IV) dose of anidulafungin 200 mg, followed by 100 mg once daily. After ≥ 5 to ≥ 10 days of IV treatment, switch to oral voriconazole/fluconazole was permitted in all but one study. Time of solid tumor diagnosis was defined as past, ≥ 6; and recent, < 6 months prior to study entry. Primary endpoint: global response of success (GRS) rate at the end of IV therapy (EOIVT). Secondary endpoints included the GRS rate at the end of all therapy (EOT), all-cause mortality, and safety. RESULTS: The GRS rate in the overall population was 73.4% at EOIVT and 65.5% at EOT. Past or recent solid tumor diagnosis did not affect GRS at EOIVT or EOT (past: 75.5% and 71.4%; recent: 72.2% and 62.2%, respectively). All-cause mortality was 14.4% on day 14 and 20.1% at day 28. Most treatment-emergent adverse events were mild/moderate in severity (81.6%). CONCLUSIONS: Treatment of IC was effective regardless of the time of solid tumor diagnosis. TRIAL REGISTRATION: Data were pooled from six studies: NCT00496197 (first posted on ClinicalTrials.gov on July 4, 2007); NCT00548262 (first posted on ClinicalTrials.gov on October 23, 2007); NCT00537329 (first posted on ClinicalTrials.gov on October 1, 2007); NCT00689338 (first posted on ClinicalTrials.gov on June 3, 2008); NCT00806351 (first posted on ClinicalTrials.gov on December 10, 2008); NCT00805740 (first posted on ClinicalTrials.gov on December 10, 2008).


Assuntos
Anidulafungina/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Neoplasias/complicações , Administração Intravenosa , Antifúngicos/administração & dosagem , Candidemia/induzido quimicamente , Fluconazol/administração & dosagem , Humanos , Resultado do Tratamento , Voriconazol/uso terapêutico
17.
J Microbiol Methods ; 184: 106202, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33722638

RESUMO

We reported a modified CFW assay for rapid detection of fungi in blood samples and evaluated its efficacy in vivo and in vitro. The positive rate, sensitivity, and negative predictive values of the modified CFW method were all significantly higher than those of traditional fungal culture and KOH methods.


Assuntos
Candidemia/microbiologia , Fungos/isolamento & purificação , Coloração e Rotulagem/métodos , Animais , Benzenossulfonatos/química , Sangue/microbiologia , Candidemia/sangue , Candidemia/diagnóstico , Testes Diagnósticos de Rotina/métodos , Feminino , Fungos/química , Humanos , Camundongos , Sensibilidade e Especificidade
18.
Mycoses ; 64(6): 684-690, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33694198

RESUMO

BACKGROUND: Intra-abdominal fungal infection (AFI) and candidemia are common in patients with acute pancreatitis (AP), but with limited and conflicting reports on their clinical impacts. This study aims to evaluate the clinical impacts of AFI and candidemia in infected pancreatic necrosis (IPN). METHODS: A single-centre, prospective cohort including 235 consecutive patients with IPN between January 2010 and September 2020 was analysed to study the clinical impacts of AFI and candidemia. RESULTS: Of the 235 patients with IPN, 69 patients (29.4%) developed AFI and 13 patients (5.5%) developed candidemia. AFI was associated with higher intestinal leakage rate (27.5% vs 12.7%, P = .006), higher pancreatic fistula rate (53.6% vs 34.3%, P = .006) and longer hospital stays (72 vs 58 days, P = .003), but with similar mortality rate compared with patients without AFI (23.2% vs 24.7%, P = .806). However, candidemia was associated with significantly higher mortality rate compared with patients without candidemia (69.2% vs 21.6%, P < .001). Patients with candidemia had higher rate of multiple organ failure and AFI (69.2% vs 36.5%, P = .018; 69.2% vs 27.0%, P = .001, respectively). Multivariable analysis showed that age ≥ 50 years (OR = 2.8; 95% CI, 1.3-5.8; P = .007), severe category (OR = 11.2; 95% CI, 3.5-35.7; P < .001), multidrug-resistant organisms infection (OR = 2.5; 95% CI, 1.0-6.2; P = .039), candidemia (OR = 11.8; 95% CI, 2.5-56.5; P = .002), step-down surgical approach (OR = 3.2; 95% CI, 1.5-7.0; P = .004) were the independent predictors associated with higher mortality in IPN patients. CONCLUSION: Although AFI did not increase the mortality of IPN, patients with candidemia carried significantly higher mortality.


Assuntos
Candidemia/mortalidade , Pancreatite Necrosante Aguda/complicações , Doença Aguda , Adulto , Feminino , Humanos , Infecções Intra-Abdominais/microbiologia , Infecções Intra-Abdominais/mortalidade , Masculino , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda/mortalidade , Pancreatite Necrosante Aguda/cirurgia , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
19.
Virulence ; 12(1): 937-950, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33729086

RESUMO

Candida parapsilosis is a leading cause of invasive mycoses and the major cause of nosocomial fungaemia amongst low and very low birth weight neonates. However, the molecular and physiological characteristics of this fungus remain understudied. To advance our knowledge about the pathobiology of this pathogen, we sought to develop and validate an effective method for chemical transformation of C. parapsilosis. Chemical transformation is the primary procedure for introducing foreign DNA into Candida yeast as it requires no special equipment, although its performance efficacy drops rapidly when the size of the transforming DNA increases. To define optimal conditions for chemical transformation in C. parapsilosis, we selected a leucine auxotroph laboratory strain. We identified optimal cell density for transformation, incubation times, inclusion of specific enhancing chemicals, and size and amounts of DNA fragments that resulted in maximized transformation efficiency. We determined that the inclusion of dimethyl sulfoxide was beneficial, but dithiothreitol pretreatment reduced colony recovery. As a result, the modified protocol led to a 20-55-fold increase in transformation efficiency, depending on the size of the transforming fragment. We validated the modified methodology with prototrophic isolates and demonstrated that the new approach resulted in the recovery of significantly more transformants in 5 of 6 isolates. Additionally, we identified a medium in which transformation competent yeast cells could safely be maintained at -80°C for up to 6 weeks that reduces laboratory work and shortens the overall procedure. These modifications will significantly aid further investigations into the genetic basis for virulence in C. parapsilosis.


Assuntos
Candida parapsilosis/genética , Candida parapsilosis/fisiologia , Transformação Bacteriana/genética , Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Candidemia/microbiologia , Leucina/metabolismo , Filogenia , Virulência/genética
20.
J Appl Microbiol ; 131(4): 2049-2060, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33694241

RESUMO

AIMS: The aim of this study was to evaluate the formation of biofilm by Candida spp. isolated from the bloodstream, using traditional spectrophotometric methodologies. In addition, the goal was to compare the results with those obtained through MALDI-TOF/MS, as well as to verify its use as a potential tool for the detection of biofilm-forming strains. METHODS AND RESULTS: Hundred and thirteen isolates of Candida spp. were studied: 41 were Candida albicans, 27 C. tropicalis, 18 C. glabrata, 17 C. parapsilosis and 10 C. krusei. Metabolic activity was determined through the tetrazolium salt (XTT) reduction assay and biomass by staining with Crystal Violet. All isolates were able to form biofilm, 94% of which were strong producers, with high biomass quantification (95%; 107/113) and high metabolic activity (99%; 112/113). Mass spectra of the biofilm-producing isolates showed differences in the intensity of mass peaks when compared with the spectra of the nonproducing strains. CONCLUSIONS: It was demonstrated that MALDI-TOF/MS was able to detect specific biofilm proteins, as the mass spectra of the isolates presented differences when compared with nonproducing strains. SIGNIFICANCE AND IMPACT OF THE STUDY: MALDI-TOF/MS can become a valuable tool for biofilm detection at the moment of the identification of the microorganism, thus contributing greatly to the management of patients with Candidemia.


Assuntos
Candida , Candidemia , Biofilmes , Candida albicans , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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