Genotypic and phenotypic characterisation of a nosocomial outbreak of Candida auris in Spain during 5 years.

OBJECTIVES: The investigation of Candida auris outbreaks is needed to provide insights into its population structure and transmission dynamics. We genotypically and phenotypically characterised a C. auris nosocomial outbreak occurred in Consorcio Hospital General Universitario de Valencia (CHGUV), Spain. METHODS: Data and isolates were collected from CHGUV from September 2017 (first case) until September 2021. Thirty-five isolates, including one from an environmental source, were randomly selected for whole genome sequencing (WGS), and the genomes were analysed along with a database with 335 publicly available genomes, assigning them to one of the five major clades. In order to identify polymorphisms associated with drug resistance, we used the fully susceptible GCA_003014415.1 strain as reference sequence. Known mutations in genes ERG11 and FKS1 conferring resistance to fluconazole and echinocandins, respectively, were investigated. Isolates were classified into aggregating or non-aggregating. RESULTS: All isolates belonged to clade III and were from an outbreak with a single origin. They clustered close to three publicly available genomes from a hospital from where the first patient was transferred, being the probable origin. The mutation VF125AL in the ERG11 gene, conferring resistance to fluconazole, was present in all the isolates and one isolate also carried the mutation S639Y in the FKS1 gene. All the isolates had a non-aggregating phenotype (potentially more virulent). CONCLUSIONS: Isolates are genotypically related and phenotypically identical but one with resistance to echinocandins, which seems to indicate that they all belong to an outbreak originated from a single isolate, remaining largely invariable over the years. This result stresses the importance of implementing infection control practices as soon as the first case is detected or when a patient is transferred from a setting with known cases.

Candida auris from colonisation to candidemia: A four-year study.

BACKGROUND: Candida auris has become a worrisome multi-drug resistant healthcare-associated pathogen due to its capacity to colonise patients and surfaces and to cause outbreaks of invasive infections in critically ill patients. OBJECTIVES: This study evaluated the outbreak in our setting in a 4-year period, reporting the risk factors for developing candidemia in previously colonised patients, the therapeutic measures for candidemia and the outcome of candidemia and colonisation cases among all C. auris isolates and their susceptibility to antifungals. METHODS: Data were retrospectively collected from patients admitted to Consorcio Hospital General Universitario de Valencia (Spain) from September 2017 to September 2021. A retrospective case-control study was designed to identify risk factors for developing C. auris candidemia in previously colonised patients. RESULTS: C. auris affected 550 patients, of which 210 (38.2%) had some clinical sample positive. Isolates were uniformly resistant to fluconazole, 20 isolates were resistant to echinocandins (2.8%) and four isolates were resistant to ampfotericin B (0.6%). There were 86 candidemia cases. APACHE II, digestive disease and catheter isolate were proven to be independent risk factors for developing candidemia in previously colonised patients. Thirty-day mortality rate for C. auris candidemia cases was 32.6%, while for colonisation cases was 33.7%. CONCLUSIONS: Candidemia was one of the most frequent and severe infections caused by C. auris. The risk factors identified in this study should help to detect patients who are at more risk of developing candidemia, as long as an adequate surveillance of C. auris colonisation is performed.

Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays.

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.

[Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2014]. / Análisis de resultados del Programa de Control de Calidad Externo de carga viral del VIH-1, del VHC y del VHB. Año 2014.

Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarizes the results obtained from the 2014 SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of 5 standards were sent. One standard consisted in seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (30.8% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 95.8% of laboratories reporting results within the limits (Δ < 0.5 log10 copies/mL). The HBV and HCV program consisted of 2 standards with different viral load contents. Most of the participants, 83.7% in the case of HCV and 87.9% in the HBV, obtained all the results within the accepted range (mean ± 1.96 standard deviations log10 IU/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up.

[Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2012]. / Análisis de resultados del Programa de Control de Calidad Externo de carga viral del VIH-1, del VHC y del VHB. Año 2012.

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2012 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (22.3% on average) obtained values out of the accepted range (mean±0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (Δ < 0.5 log10 copias/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 84% in the case of HCV and 88% in the HBV, obtained all the results within the accepted range (mean±1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up.

[Analysis of the results of the HIV-1, HCV and HBV viral load of the SEIMC External Quality Control Program. Year 2011]. / Análisis de resultados del Programa de Control de Calidad Externo de carga viral del VIH-1, del VHC y del VHB. Año 2011.

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers in the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarizes the results of the 2011 SEIMC External Quality Control Program for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients in the range of 2-5 log10 copies/mL; to determine repeatability, two of these standards were identical. A significant proportion of the laboratories (52.1% on average) obtained values outside the accepted range (mean ± 0,25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 94.9% of laboratories reporting results within the accepted range (Δ<0,5 log10 copies/ mL). The HBV and HCV program consisted of two standards with different viral load contents. In most of the participating laboratories (90% in the case of HCV and 86% in that of HBV), all the results were within the accepted range (mean ± 1.96 SD log10UI/mL). Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to the marked interlaboratory variability found, use of the same method and the same laboratory for patient follow-up is advisable.

[Analysis of the results of the SEIMC External Quality Control Program, 2007]. / Análisis de resultados del Programa Externo de Control de Calidad SEIMC. Año 2007.

The External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) includes controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology and molecular microbiology. This article presents the most important conclusions and lessons drawn from the 2007 controls. As a whole, the results obtained in 2007 confirm the excellent skill and good technical standards found in previous years. However, erroneous results can be obtained in any laboratory and in clinically relevant determinations. A few deviations were observed in some controls, calling for critical reflection. Once again, the results of this program highlighted the need to complement internal with external controls, such as those offered by the SEIMC program.

[Analysis of the results of the SEIMC External Quality Control Program for HIV-1 and HCV viral loads, 2007]. / Análisis de resultados del Programa Externo de Control de Calidad SEIMC de carga viral del VIH-1 y del VHC. Año 2007.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) viral load determinations are among the most important tasks performed in the molecular microbiology laboratory, due to their importance in patient follow-up. Quality control tools are crucial in these laboratories to ensure the accuracy of the results. This article presents the analysis of the results obtained in 2007 from the SEIMC External Quality Control Program for HIV-1 and HCV viral loads. METHODS AND RESULTS: In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in a range of 2-5 log(10) copies/mL; to analyze repeatability, two of these standards were identical. The specificity was good for all the methods used by the participants, and only two out of 75 results were considered to be false positive results. A substantial proportion of the laboratories (20% on average) obtained values outside the accepted range (mean +/-0.2 log(10) copies/mL), depending on the standard and on the method used for quantification. A few errors were due to the transcription of the analytical result. Repeatability was also acceptable but approximately 15% of laboratories failed this evaluation. The HCV program consisted of two standards with different viral load contents. Most of the participants (94.6%) obtained results within the accepted range (mean +/-1.96 SD log(10) UI/mL), and interlaboratory variability was <0.5 log units for both standards and all techniques. CONCLUSIONS: Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to wide interlaboratory variability, the use of the same method and the same laboratory for patient follow-up is advisable.