ABSTRACT
Candida albicans is a common fungal pathogen and amongst the leading causes of invasive candidiasis globally. This systematic review examines the characteristics and global impact of invasive infections caused by C. albicans. We searched on PubMed and Web of Science for studies reporting on criteria such as mortality, morbidity, drug resistance, preventability, yearly incidence, and distribution/emergence during the period from 2016 to 2021. Our findings indicate that C. albicans is the most common Candida species causing invasive disease and that standard infection control measures are the primary means of prevention. However, we found high rates of mortality associated with infections caused by C. albicans. Furthermore, there is a lack of data on complications and sequelae. Resistance to commonly used antifungals remains rare. Although, whilst generally susceptible to azoles, we found some evidence of increasing resistance, particularly in middle-income settings-notably, data from low-income settings were limited. Candida albicans remains susceptible to echinocandins, amphotericin B, and flucytosine. We observed evidence of a decreasing proportion of infections caused by C. albicans relative to other Candida species, although detailed epidemiological studies are needed to confirm this trend. More robust data on attributable mortality, complications, and sequelae are needed to understand the full extent of the impact of invasive C. albicans infections.
Subject(s)
Antifungal Agents , Candida albicans , Drug Resistance, Fungal , Humans , Candida albicans/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , World Health Organization , Candidiasis/epidemiology , Candidiasis/microbiology , Candidiasis/mortality , Candidiasis, Invasive/epidemiology , Candidiasis, Invasive/microbiology , Candidiasis, Invasive/mortality , Global Health , IncidenceABSTRACT
BACKGROUND: Candida auris is an emerging and multidrug-resistant pathogen. Here we report the epidemiology of a hospital outbreak of C. auris colonization and infection. METHODS: After identification of a cluster of C. auris infections in the neurosciences intensive care unit (ICU) of the Oxford University Hospitals, United Kingdom, we instituted an intensive patient and environmental screening program and package of interventions. Multivariable logistic regression was used to identify predictors of C. auris colonization and infection. Isolates from patients and from the environment were analyzed by whole-genome sequencing. RESULTS: A total of 70 patients were identified as being colonized or infected with C. auris between February 2, 2015, and August 31, 2017; of these patients, 66 (94%) had been admitted to the neurosciences ICU before diagnosis. Invasive C. auris infections developed in 7 patients. When length of stay in the neurosciences ICU and patient vital signs and laboratory results were controlled for, the predictors of C. auris colonization or infection included the use of reusable skin-surface axillary temperature probes (multivariable odds ratio, 6.80; 95% confidence interval [CI], 2.96 to 15.63; P<0.001) and systemic fluconazole exposure (multivariable odds ratio, 10.34; 95% CI, 1.64 to 65.18; P=0.01). C. auris was rarely detected in the general environment. However, it was detected in isolates from reusable equipment, including multiple axillary skin-surface temperature probes. Despite a bundle of infection-control interventions, the incidence of new cases was reduced only after removal of the temperature probes. All outbreak sequences formed a single genetic cluster within the C. auris South African clade. The sequenced isolates from reusable equipment were genetically related to isolates from the patients. CONCLUSIONS: The transmission of C. auris in this hospital outbreak was found to be linked to reusable axillary temperature probes, indicating that this emerging pathogen can persist in the environment and be transmitted in health care settings. (Funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University and others.).
Subject(s)
Candida , Candidiasis/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Equipment Contamination , Equipment Reuse , Infection Control/methods , Intensive Care Units , Thermometers/microbiology , Adult , Candida/genetics , Candida/isolation & purification , Candidiasis/mortality , Candidiasis/transmission , Case-Control Studies , Cross Infection/mortality , Cross Infection/transmission , Female , Hospital Departments , Humans , Incidence , Male , Microbial Sensitivity Tests , Middle Aged , Multivariate Analysis , Neurology , Phylogeny , Risk Factors , United Kingdom/epidemiologyABSTRACT
BACKGROUND: The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes. METHODS: All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed. RESULTS: Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not. CONCLUSIONS: The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.
Subject(s)
Antifungal Agents/therapeutic use , Candida/drug effects , Candida/isolation & purification , Cross Infection/epidemiology , Cross Infection/microbiology , Sepsis/epidemiology , Sepsis/microbiology , Adult , Aged , Candidiasis/epidemiology , Candidiasis/microbiology , Candidiasis/mortality , China/epidemiology , Cross Infection/drug therapy , Cross Infection/mortality , Female , Humans , Incidence , Inpatients , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Risk Factors , Sepsis/drug therapy , Sepsis/mortality , Tertiary Care Centers , Treatment OutcomeABSTRACT
BACKGROUND: Candida is the common conditionally pathogenic fungus that infected human and animal clinically. C. tropicalis had been isolated from the skin and hair of healthy pigs, but with no report of fatal infection in gastrointestinal diseases. CASE PRESENTATION: In a pig farm in Henan Province of China, about 20 % of pregnant and postpartum sows suffered from severe gastrointestinal diseases, with a mortality rate higher than 60 % in the diseased animals. The sows had gastrointestinal symptoms such as blood in stool and vomiting. Necropsy revealed obvious gastric ulcers, gastrointestinal perforation, and intestinal hemorrhage in the gastrointestinal tract, but no lesions in other organs. The microbial species in gastric samples collected from gastric ulcer of the diseased sows then was initially identified as Candida by using routine systems of microscopic examination, culture characteristics on the medium Sabouraud dextrose agar medium. The fungus was further identified as C. tropicalis by species-specific PCR and sequencing. This study revealed an infection of C. tropicalis in sows through gastrointestinal mucosa could cause fatal digestive system disease and septicemia. CONCLUSIONS: For the first time, a strain of C. tropicalis was isolated and identified from the gastric tissue of sows with severe gastrointestinal diseases. PCR and sequencing of ITS-rDNA combined with morphology and histopathological assay were reliable for the identification of Candida clinically.
Subject(s)
Candida tropicalis/isolation & purification , Candidiasis/veterinary , Gastrointestinal Diseases/veterinary , Swine Diseases/microbiology , Animal Feed/adverse effects , Animals , Candida tropicalis/classification , Candida tropicalis/genetics , Candidiasis/mortality , Candidiasis/pathology , China/epidemiology , DNA, Ribosomal , Female , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/mortality , Gastrointestinal Diseases/pathology , Polymerase Chain Reaction/veterinary , Swine , Swine Diseases/mortalityABSTRACT
BACKGROUND: Treatment of Candida albicans bloodstream infection with fluconazole is associated with significant mortality despite in vitro susceptibility to the drug. OBJECTIVES: We sought to determine whether tolerance to fluconazole is predictive of treatment failure. METHODS: We reviewed patients with monomicrobial C albicans bloodstream infection who received primary monotherapy with fluconazole. Tolerance to fluconazole, defined as the fraction of growth above the MIC, was quantified using the disc diffusion assay and digital image analyses. Survival analyses were performed with host and treatment factors as predictive variables. RESULTS: Among 44 patients included in the study, all-cause mortality was 29.5% at 30 days and 43.1% at 12 weeks. Forty-one isolates (93%) were susceptible to fluconazole (MIC50, 0.5 mg/L). Fluconazole tolerance was strongly associated with death for patients treated with fluconazole within 24 h of candidemia onset (33.3% vs 0%; p = .007), but not among patients whose treatment was started later. MIC did not correlate with survival, regardless of treatment delay. A Cox regression model including time to treatment, tolerance to fluconazole, fluconazole exposure and Pitt bacteraemia score provided good prediction of treatment outcome (area under the receiver-operator curve, 0.82). CONCLUSIONS: In patients with C albicans bloodstream infection, tolerance testing was predictive of fluconazole efficacy if the drug was started early. Further study is required to validate the utility of this metric to guide treatment choices.
Subject(s)
Antifungal Agents/therapeutic use , Candidemia/drug therapy , Candidiasis/drug therapy , Fluconazole/therapeutic use , Adult , Aged , Aged, 80 and over , Candida albicans , Candidiasis/mortality , Cohort Studies , Drug Resistance, Fungal , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Survival Analysis , Treatment Failure , Treatment OutcomeABSTRACT
This study detailed the responses of Galleria mellonella larvae to disseminated infection caused by co-infection with Candida albicans and Staphylococcus aureus. Doses of C. albicans (1×105 larva-1) and S. aureus (1×104 larva-1) were non-lethal in mono-infection but when combined significantly (P<0.05) reduced larval survival at 24, 48 and 72 h relative to larvae receiving S. aureus (2×104 larva-1) alone. Co-infected larvae displayed a significantly higher density of S. aureus larva-1 compared to larvae infected solely with S. aureus. Co-infection resulted in dissemination throughout the host and the appearance of large nodules. Co-infection of larvae with C. albicans and S. aureus (2×104 larva-1) resulted in an increase in the density of circulating haemocytes compared to that in larvae infected with only S. aureus. Proteomic analysis of co-infected larval haemolymph revealed increased abundance of proteins associated with immune responses to bacterial and fungal infection such as cecropin-A (+45.4-fold), recognition proteins [e.g. peptidoglycan-recognition protein LB (+14-fold)] and proteins associated with nodule formation [e.g. Hdd11 (+33.3-fold)]. A range of proteins were also decreased in abundance following co-infection, including apolipophorin (-62.4-fold), alpha-esterase 45 (-7.7-fold) and serine proteinase (-6.2-fold). Co-infection of larvae resulted in enhanced proliferation of S. aureus compared to mono-infection and an immune response showing many similarities to the innate immune response of mammals to infection. The utility of G. mellonella larvae for studying polymicrobial infection is highlighted.
Subject(s)
Candida albicans/physiology , Coinfection/immunology , Moths/microbiology , Staphylococcus aureus/pathogenicity , Animals , Antimicrobial Cationic Peptides/metabolism , Bacterial Load , Candidiasis/immunology , Candidiasis/microbiology , Candidiasis/mortality , Coinfection/microbiology , Coinfection/mortality , Disease Models, Animal , Hemocytes/metabolism , Hemolymph/cytology , Hemolymph/metabolism , Insect Proteins/metabolism , Larva/microbiology , Proteomics , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortality , Staphylococcus aureus/growth & development , Survival RateABSTRACT
BACKGROUND: Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris. METHODS: We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0. RESULTS: It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%). CONCLUSIONS: Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management.
Subject(s)
Candida/drug effects , Candidiasis/epidemiology , Candidiasis/mortality , Amphotericin B/therapeutic use , Anidulafungin/therapeutic use , Antifungal Agents/therapeutic use , Candida/classification , Candida/genetics , Candidiasis/drug therapy , Candidiasis/microbiology , Caspofungin/therapeutic use , Drug Resistance, Multiple, Fungal/drug effects , Fluconazole/therapeutic use , Humans , Micafungin/therapeutic use , PrevalenceABSTRACT
PURPOSE: The purpose of this study was to explore the clinical features, risk factors, and outcomes of mixed Candida albicans/bacterial bloodstream infections (mixed-CA/B-BSIs) compared with monomicrobial Candida albicans bloodstream infection (mono-CA-BSI) in adult patients in China. METHODS: All hospitalized adults with Candida albicans bloodstream infection (CA-BSI) were recruited for this retrospective observational study from January 1, 2013, to December 31, 2018. RESULTS: Of the 117 patients with CA-BSI, 24 patients (20.5%) had mixed-CA/B-BSIs. The most common copathogens were coagulase-negative Staphylococcus (CNS) (24.0%), followed by Klebsiella pneumoniae (20.0%) and Staphylococcus aureus (16.0%). In the multivariable analysis, a prior ICU stay > 2 days (adjusted odds ratio [OR], 7.445; 95% confidence interval [CI], 1.152-48.132) was an independent risk factor for mixed-CA/B-BSIs. Compared with patients with mono-CA-BSI, patients with mixed-CA/B-BSIs had a prolonged length of mechanical ventilation [17.5 (4.5, 34.8) vs. 3.0 (0.0, 24.5), p = 0.019] and prolonged length of ICU stay [22.0 (14.3, 42.2) vs. 8.0 (0.0, 31.5), p = 0.010]; however, mortality was not significantly different. CONCLUSIONS: There was a high rate of mixed-CA/B-BSIs cases among CA-BSI cases, and CNS was the predominant coexisting species. A prior ICU stay > 2 days was an independent risk factor for mixed -CA/B-BSIs. Although there was no difference in mortality, the outcomes of patients with mixed -CA/B-BSIs, including prolonged length of mechanical ventilation and prolonged length of ICU stay, were worse than those with mono-CA-BSI; this deserves further attention from clinicians.
Subject(s)
Bacteremia/complications , Candida albicans/isolation & purification , Candidiasis/complications , Klebsiella Infections/complications , Klebsiella pneumoniae/isolation & purification , Staphylococcal Infections/complications , Staphylococcus aureus/isolation & purification , Aged , Bacteremia/microbiology , Bacteremia/mortality , Candidiasis/microbiology , Candidiasis/mortality , China/epidemiology , Cross Infection/microbiology , Female , Humans , Kaplan-Meier Estimate , Klebsiella Infections/microbiology , Klebsiella Infections/mortality , Male , Middle Aged , Respiration, Artificial/adverse effects , Retrospective Studies , Risk Factors , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortalityABSTRACT
BACKGROUND: Secondary infection is an important factor affecting mortality and quality of life in patients with severe acute pancreatitis. The characteristics of secondary infection, which are well known to clinicians, need to be re-examined in detail, and their understanding among clinicians needs to be updated accordingly. AIM: This study aims to investigate the characteristics and drug resistance of pathogens causing severe acute pancreatitis (SAP) secondary infection, to objectively present infection situation, and to provide reference for improved clinical management. METHODS: A retrospective analysis was performed on 55 consecutive patients with SAP who developed secondary infection with an accurate evidence of bacterial/fungal culture from 2016 to 2018. The statistics included the spectrum and distribution of pathogens, the drug resistance of main pathogens, and associations between multiple infectious parameters and mortality. RESULTS: A total of 181 strains of pathogens were isolated from (peri)pancreas; bloodstream; and respiratory, urinary, and biliary systems in 55 patients. The strains included 98 g-negative bacteria, 58 g-positive bacteria, and 25 fungi. Bloodstream infection (36.5%) was the most frequent infectious complication, followed by (peri)pancreatic infection (32.0%). Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Stenotrophomonas maltophilia were predominant among gram-negative bacteria. Gram-positive bacterial infections were mainly caused by Enterococcus faecium and Staphylococcus spp. Fungal infections were predominantly caused by Candida spp. The drug resistance of pathogens causing SAP secondary infection was generally higher than the surveillance level. Patients in the death group were older (55 ± 13 years vs. 46 ± 14 years; p = 0.039) and had longer intensive care unit (ICU) stay (14 vs. 8; p = 0.026) than those in the survival group. A. baumannii infection (68.4% vs. 33%; p = 0.013), number of pathogens ≥ 4 (10 vs. 6; p = 0.005), pancreatic infection (14 vs. 15, p = 0.024), and urinary infection (8 vs. 5; p = 0.019) were significantly associated with mortality. CONCLUSION: Gram-negative bacteria are the main pathogens causing SAP secondary infection, in which nosocomial infections play a major role. The drug resistance profile of gram-negative bacteria is seriously threatening, and the commonly used antibiotics in SAP are gradually losing their effectiveness. Much attention should be paid to the rational use of antibiotics, and strategies should be established for infection prevention in SAP.
Subject(s)
Candidiasis/microbiology , Cross Infection/microbiology , Drug Resistance, Microbial , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/microbiology , Pancreatitis/therapy , Acinetobacter baumannii , Adult , Aged , Bacteremia/complications , Bacteremia/drug therapy , Bacteremia/microbiology , Bacteremia/mortality , Biliary Tract Diseases/complications , Biliary Tract Diseases/drug therapy , Biliary Tract Diseases/microbiology , Biliary Tract Diseases/mortality , Candida , Candidemia/complications , Candidemia/drug therapy , Candidemia/microbiology , Candidemia/mortality , Candidiasis/complications , Candidiasis/drug therapy , Candidiasis/mortality , Cause of Death , Coinfection/complications , Coinfection/drug therapy , Coinfection/microbiology , Coinfection/mortality , Cross Infection/complications , Cross Infection/drug therapy , Cross Infection/mortality , Enterococcus faecium , Escherichia coli , Female , Gram-Negative Bacterial Infections/complications , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/mortality , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/mortality , Hospital Mortality , Hospitals, Teaching , Hospitals, University , Humans , Intensive Care Units , Intraabdominal Infections/complications , Intraabdominal Infections/drug therapy , Intraabdominal Infections/microbiology , Intraabdominal Infections/mortality , Klebsiella pneumoniae , Length of Stay , Male , Middle Aged , Pancreatitis/complicationsABSTRACT
BACKGROUND: Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in surgical intensive care patients. The purpose of this study was to investigate the impact of appropriate source control and antifungal therapy on the outcomes of critically ill surgical patients with IAC. METHODS: This was a retrospective single-center cohort study. Adult surgical patients who were admitted to the intensive care unit and diagnosed with IAC from January 1, 2003, to December 31, 2016, were enrolled. The patients' data including risk factors of IAC, infection-related information, antifungal treatment and 30-day outcomes were collected. The primary endpoint was 30-day mortality. A COX proportional hazards model was used to analyze the association between appropriate treatment and 30-day survival. RESULTS: A total of 82 patients were included in the analysis. Of these, 45 (54.9%) were complicated with septic shock at IAC diagnosis. Types of IAC included peritonitis (61.0%), intra-abdominal abscesses (23.2%) and biliary tract infections (15.9%). Of the included patients, 53 (64.6%) received appropriate source control and 44 (53.7%) appropriate antifungal therapy. Compared with patients with neither of these treatments, appropriate source control (HR 0.08, 95% CI 0.02-0.30; P < 0.001), appropriate antifungal therapy (HR 0.14, 95% CI 0.04-0.55; P = 0.005), and a combination of these treatments (HR 0.02, 95% CI 0.00-0.08; P < 0.001) were associated with reduced risk of death within 30 days after IAC diagnosis. CONCLUSION: For critically ill surgical patients with IAC, both appropriate source control and appropriate antifungal therapy were associated with reduced risk of 30-day mortality, and the protective effects of the two appropriate treatments were additive.
Subject(s)
Abdominal Abscess/therapy , Antifungal Agents/therapeutic use , Candidiasis/therapy , Critical Care/methods , Peritonitis/therapy , Surgical Wound Infection/therapy , Abdominal Abscess/etiology , Abdominal Abscess/mortality , Adult , Aged , Aged, 80 and over , Candidiasis/etiology , Candidiasis/mortality , Combined Modality Therapy , Critical Illness , Female , Follow-Up Studies , Humans , Intensive Care Units , Male , Middle Aged , Peritonitis/etiology , Peritonitis/mortality , Proportional Hazards Models , Retrospective Studies , Risk Factors , Surgical Wound Infection/mortality , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Candida auris is a difficult-to-diagnose multidrug-resistant yeast that can cause invasive infections with high mortality. Since emerging in 2009, this pathogen has been associated with numerous outbreaks around the world. Whole genome sequencing (WGS) is instrumental for understanding the emergence and local transmission of this pathogen. OBJECTIVES: To describe the clinical, molecular characteristics of Candida auris infection and clinical outcome in our centre. PATIENTS AND METHODS: Patients with positive cultures for Candida auris were identified in a microbiology database. Clinical characteristics and antifungal susceptibility were obtained. Isolates were sent to the US CDC for whole genome sequencing. RESULTS: Seven unique patients with eight different isolates were identified. Seven isolates were sent to the US CDC for whole genome sequencing. None of the patients had bloodstream infection. Thirty-day mortality was higher in infected patients compared with those who were colonised. Seven of the eight isolates were resistant to both fluconazole, and five were resistant to amphotericin B. WGS analysis demonstrated that the seven isolates belonged to the South Asian clade but formed two distinct subclades suggesting two independent introductions and ongoing transmission within the facility. CONCLUSIONS: Candida auris is associated with a high mortality rate in infected patients. Strict infection control measures and surveillance for asymptomatic cases are warranted to halt ongoing transmission.
Subject(s)
Candida/genetics , Candidiasis/microbiology , Candidiasis/transmission , Adult , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Asymptomatic Infections , Candida/pathogenicity , Candidiasis/mortality , Disease Outbreaks , Drug Resistance, Multiple, Fungal , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Polymorphism, Single Nucleotide , Saudi Arabia , Treatment Outcome , Whole Genome SequencingABSTRACT
Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, amphotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre-emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination.
Subject(s)
Antifungal Agents/therapeutic use , Candida/isolation & purification , Candidiasis/diagnosis , Candidiasis/drug therapy , Candidiasis/prevention & control , Age Factors , Australia , Candida/drug effects , Candida/genetics , Candidiasis/mortality , Cross Infection/prevention & control , DNA, Fungal/genetics , Disease Transmission, Infectious/prevention & control , Drug Resistance, Fungal , Fluconazole/therapeutic use , Humans , Infection Control/methods , Microbial Sensitivity Tests , New Zealand , Societies, MedicalABSTRACT
Candida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality. C. auris strains often demonstrate high fluconazole and amphotericin B MIC values, and some strains are resistant to all three major antifungal classes. We evaluated the susceptibility of 16 C. auris clinical strains, isolated from a wide geographical area, to 10 antifungal agents, including APX001A, a novel agent that inhibits the fungal protein Gwt1 (glycosylphosphatidylinositol-anchored wall transfer protein 1). APX001A demonstrated significantly lower MIC50 and MIC90 values (0.004 and 0.031 µg/ml, respectively) than all other agents tested. The efficacy of the prodrug APX001 was evaluated in an immunocompromised murine model of disseminated C. auris infection. Significant efficacy (80 to 100% survival) was observed in all three APX001 treatment groups versus 50% survival for the anidulafungin treatment group. In addition, APX001 showed a significant log reduction in CFU counts in kidney, lung, and brain tissue (1.03 to 1.83) versus the vehicle control. Anidulafungin also showed a significant log reduction in CFU in the kidneys and lungs (1.5 and 1.62, respectively) but did not impact brain CFU. These data support further clinical evaluation of this new antifungal agent.
Subject(s)
Aminopyridines/pharmacology , Antifungal Agents/pharmacology , Candida/drug effects , Candidiasis/drug therapy , Candidiasis/immunology , Immunocompromised Host , Isoxazoles/pharmacology , Prodrugs/pharmacology , Aminopyridines/metabolism , Amphotericin B/pharmacology , Anidulafungin/pharmacology , Animals , Antifungal Agents/metabolism , Brain/drug effects , Brain/microbiology , Candida/growth & development , Candidiasis/microbiology , Candidiasis/mortality , Dose-Response Relationship, Drug , Echinocandins/pharmacology , Female , Fluconazole/pharmacology , Isoxazoles/metabolism , Kidney/drug effects , Kidney/microbiology , Lung/drug effects , Lung/microbiology , Mice , Microbial Sensitivity Tests , Prodrugs/metabolism , Survival AnalysisABSTRACT
Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.
Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Candida/isolation & purification , Candidiasis/diagnosis , Adult , Aged , Antifungal Agents/therapeutic use , Candida/pathogenicity , Candidiasis/epidemiology , Candidiasis/mortality , Drug Resistance, Multiple, Fungal , Female , Humans , Intensive Care Units , Male , Microbial Sensitivity Tests , Middle Aged , Panama/epidemiology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Young AdultABSTRACT
A French single-centre retrospective study between 2010 and 2014 was undertaken to assess candiduria's incidence in kidney transplant recipients (KTR), and the use and impact of antifungal treatment on outcome. Candiduria was defined as a urine culture with ≥103 cfu/mL of Candida species. Candiduria clearance, severe complications and death rates were estimated by Kaplan-Meier methods and the effect of treatment by Cox models. 52/1223 (4.3%) KTR had ≥1 episode of candiduria, 42 (81%) were females, 18 (35%) had diabetes, with an incidence of 2.3/100 person-year of follow-up. Candiduria was asymptomatic in 51 (98%) patients. Candida glabrata was the most frequent pathogen identified. Overall fungal clearance rate was 89%. Antifungal therapy was initiated in only 14 episodes (12%), according to guidelines. Three patients (6%) developed severe complications in the first 2 weeks after transplantation, and 8 (15%) died. Antifungal treatment had no impact on candiduria clearance (HR, 0.6; 95% CI, 0.3-1.1; P = .10), on recurrence rate (HR, 0.5; 95% CI, 0.1-2.3; P = .41) and on the risk of severe complications or death (HR, 1.1; 95% CI, 0.3-4.8; P = .89). Candiduria is rare and usually asymptomatic among KTR. Candiduria management in the immediate post-transplant period deserves careful attention.
Subject(s)
Antifungal Agents/therapeutic use , Candida/drug effects , Candidiasis/drug therapy , Transplant Recipients , Urinary Tract Infections/drug therapy , Adult , Aged , Antifungal Agents/adverse effects , Candida/classification , Candida/isolation & purification , Candidiasis/complications , Candidiasis/mortality , Candidiasis/urine , Female , Humans , Incidence , Kidney Transplantation/adverse effects , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Treatment Outcome , Urinary Tract Infections/microbiology , Urinary Tract Infections/mortalityABSTRACT
Candida albicans is a commensal microorganism in the oral cavity and gastrointestinal and urogenital tracts of most individuals that acts as an opportunistic pathogen when the host immune response is reduced. Here, we established different immunocompetent murine models to analyze the antibody responses to the C. albicans proteome during commensalism, commensalism followed by infection, and infection (C, C+I, and I models, respectively). Serum anti-C. albicans IgG antibody levels were higher in colonized mice than in infected mice. The antibody responses during gut commensalism (up to 55 days of colonization) mainly focused on C. albicans proteins involved in stress response and metabolism and differed in both models of commensalism. Different serum IgG antibody-reactivity profiles were also found over time among the three murine models. C. albicans gut colonization protected mice from an intravenous lethal fungal challenge, emphasizing the benefits of fungal gut colonization. This work highlights the importance of fungal gut colonization for future immune prophylactic therapies.
Subject(s)
Antibodies, Fungal/blood , Candida albicans/immunology , Candidiasis/immunology , Fungal Proteins/immunology , Host-Pathogen Interactions , Immunoglobulin G/blood , Animals , Candida albicans/growth & development , Candidiasis/microbiology , Candidiasis/mortality , Female , Fungal Proteins/genetics , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/microbiology , Mice , Mice, Inbred C57BL , Survival Analysis , Symbiosis/immunologyABSTRACT
Drugs that act more promiscuously provide fewer routes for the emergence of resistant mutants. This benefit, however, often comes at the cost of serious off-target and dose-limiting toxicities. The classic example is the antifungal amphotericin B (AmB), which has evaded resistance for more than half a century. We report markedly less toxic amphotericins that nevertheless evade resistance. They are scalably accessed in just three steps from the natural product, and they bind their target (the fungal sterol ergosterol) with far greater selectivity than AmB. Hence, they are less toxic and far more effective in a mouse model of systemic candidiasis. To our surprise, exhaustive efforts to select for mutants resistant to these more selective compounds revealed that they are just as impervious to resistance as AmB. Thus, highly selective cytocidal action and the evasion of resistance are not mutually exclusive, suggesting practical routes to the discovery of less toxic, resistance-evasive therapies.
Subject(s)
Amphotericin B/chemical synthesis , Antifungal Agents/chemical synthesis , Candida/drug effects , Candidiasis/drug therapy , Drug Resistance, Fungal/drug effects , Urea/chemistry , Amphotericin B/analogs & derivatives , Amphotericin B/pharmacology , Animals , Antifungal Agents/pharmacology , Binding Sites , Candida/chemistry , Candida/growth & development , Candida/pathogenicity , Candidiasis/microbiology , Candidiasis/mortality , Cell Line , Cell Survival/drug effects , Epithelial Cells/cytology , Epithelial Cells/drug effects , Ergosterol/chemistry , Ergosterol/metabolism , Humans , Mice , Microbial Viability/drug effects , Structure-Activity Relationship , Survival AnalysisABSTRACT
Early empiric therapy and adequate resuscitation have been identified as main predictors of outcome in patients with candidemia or bacteremia. Moreover, source control is a major determinant in infectious sites when feasible, as a main technique to reduce microbiological burden. A retrospective, multicenter, cohort study was performed at surgical wards and intensive care units (ICU) of three University Hospitals in Spain between 2010 and 2014, with the aim of improving understanding of the interaction between source control, early antifungal therapy, and use of vasoactives in patients with intra-abdominal candidiasis (IAC). Source control was defined as all physical actions taken to control a focus of infection and reduce the favorable conditions that promote microorganism growth or that maintain the impairment of host defenses. Two hundred and fifty-eight patients with IAC were identified. Sixty-one patients were at ICU for diagnosis. Mortality was higher in the ICU group compared to what was documented for the non-ICU group (35 % vs 19.5 %, p = 0011). Adequate source control within 48 h of diagnosis was achieved in 60 % of the cohort. In multivariate analysis, inadequate source control was identified as the only common risk factor for 30-day mortality in both groups (ICU group OR: 13.78 (95% CI: 2.60-72.9, p = 0.002) and non-ICU group OR: 6.53 (95% CI: 2.56-16.61, p = <0.001). The population receiving both adequate source control and adequate antifungal treatment was the one associated with a higher survival rate, in both the ICU and surgical groups. Source control remains a key element in IAC, inside and outside the intensive care unit. Early antifungal treatment among ICU patients was associated with lower mortality.
Subject(s)
Candidiasis/mortality , Candidiasis/therapy , Intraabdominal Infections/mortality , Intraabdominal Infections/therapy , Patient Care Bundles/methods , Adult , Aged , Animals , Critical Care , Female , Hospitals, University , Humans , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Survival AnalysisABSTRACT
Candida species are commonly detected isolates from abdominal foci. The question remains as to who would benefit from early empiric treatment in cases of Candida peritonitis. This study collected real-life data on critically ill patients with Candida peritonitis to estimate the relevance of the chosen treatment strategy on the outcome of these patients. One hundred and thirty-seven surgical intensive care unit (ICU) patients with intra-abdominal invasive Candidiasis were included in the study. Fifty-six patients did not get any antifungal agent. Twenty-nine patients were empirically treated, and 52 patients were specifically treated. In the group without, with empiric and with specific antifungal treatment, the 30-day mortality rate was 33.9, 48.3 and 44.2 respectively. Candida albicans was the most frequently found species. Seven patients in the specific treatment group and one patient in the empiric treatment group emerged with candidaemia. Age, leucocyte count, APACHE II Score and acute liver failure were independent predictors of 30-day mortality in patients with Candida peritonitis. Not all patients with Candida peritonitis received antifungal treatment in real clinical practice. Patients with higher morbidity more often got antifungals. Early empirical therapy has not been associated with a better 30-day mortality.
Subject(s)
Candida/isolation & purification , Candidiasis/drug therapy , Candidiasis/mortality , Peritonitis/drug therapy , Peritonitis/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Candida/classification , Critical Illness , Female , Humans , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
To describe the epidemiology of invasive Candida infection in a tertiary care paediatric hospital. Prospective single-centre survey on all Candida strains isolated from normally sterile fluids and urines in the period 2005-2015 . A total of 299 ICI were documented in 262 patients. Urinary tract infection represented the most frequent diagnosis (62%), followed by fungaemia (34%) and peritonitis (4%). Fungaemia was most frequent in children with cancer (59%) or in low birth weight neonates (61%), while urinary tract infections were more frequent in patients with urinary tract malformation. C.albicans was the most frequently isolated species (60%) compared with C. non-albicans, but differences were present according to the site of isolation and underlying conditions. Overall 90-day mortality was 7%, 13% in fungaemias, 8% in peritonitis and 2% in urinary tract infections. The rates of invasive Candida infection increased during the study period. Invasive Candida infection is diagnosed with increasing frequency in children. Site of isolation and aetiology are frequently related with the presence of underlying, favouring conditions. Mortality was not negligible, especially in the presence of more invasive infections and specific underlying conditions.