Detection and treatment of Candida auris in an outbreak situation: risk factors for developing colonization and candidemia by this new species in critically ill patients.

BACKGROUND: Candida auris is an emerging, multidrug-resistant yeast causing hospital outbreaks. This study describes the first 24 months of the ongoing C. auris outbreak in our hospital and analyzes predisposing factors to C. auris candidemia/colonization. RESEARCH DESIGN AND METHODS: A 12-month prospective, case-controlled study was performed including a total of 228 patients (114 colonized/candidemia and 114 controls). Data from the first 79 candidemia episodes and 738 environmental samples were also analyzed. Definitive C. auris identification was performed by ITS sequencing. Antifungal susceptibility was carried out by EUCAST methodology. RESULTS: Polytrauma (32%), cardiovascular disease (25%), and cancer (17%) were the most common underlying condition in colonized/candidemia patients. Indwelling CVC (odds ratio {OR}, 13.48), parenteral nutrition (OR, 3.49), and mechanical ventilation (OR, 2.43) remained significant predictors of C. auris colonization/candidemia. C. auris was most often isolated on sphygmomanometer cuffs (25%) patient tables (10.2%), keyboards (10.2%), and infusion pumps (8.2%). All isolates were fully resistant to fluconazole (MICs >64 mg/L) and had significantly reduced susceptibility to voriconazole (GM, 1.8 mg/L). CONCLUSIONS: Predictor conditions to C. auris colonization/candidemia are similar to other Candida species. C. auris colonizes multiple patient's environment surfaces. All isolates are resistant to fluconazole and had significant reduced susceptibility to voriconazole.

Influence of antibiotic pressure on multi-drug resistant Klebsiella pneumoniae colonisation in critically ill patients.

Background: The aim of this study is to evaluate the risk factors for colonisation by multidrug resistant (MDR) K. pneumoniae in a critical care unit and the relationship between colonisation and the antibiotic pressure exerted by the antimicrobial treatments received by patients. Methods: A prospective observational was designed. Patients admitted for more than 48 h to an intensive care unit were included. Samples for surveillance cultures were obtained from all the patients upon admission and once a week. The association between risk factors and colonisation by MDR K. pneumoniae was determined by logistic regression. A Cox regression model was used to evaluate the effect of the use of antimicrobials on the colonisation rate. An ARMIA model was used to investigate the association between the incidence of colonisation by MDR strains and the global consumption of antimicrobials in the unit. Results: One thousand seven hundred twenty-five patients were included, from which 308 (17.9%) were positive for MDR K. pneumoniae. In the multivariate analysis, hospitalisation for longer than 7 days together with respiratory infection and administration of any antibiotic was associated with increased MR K. pneumoniae colonisation. Patients who received antibiotics for more than 48 h were colonised earlier than patients who did not receive antibiotic treatment [HR: 2.16 (95%CI:1.55-3.03)]. The ARIMA model found a significant association between the monthly colonisation rate for MR K. pneumoniae and the consumption of cephalosporins and carbapenems in the previous month. Conclusion: Individual antibiotic administration and the global antibiotic pressure of cephalosporins and carbapenems are associated to an increased colonisation by MDR K. pneumoniae strains.

Vancomycin and daptomycin minimum inhibitory concentrations as a predictor of outcome of methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: The aim of this study was to determine the persistence of the adverse prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting with low vancomycin use. METHODS: A retrospective study focusing on episodes of bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was designed. The main outcome measures were 30-day mortality and treatment failure. Multivariate logistic regression analysis was used to identify variables associated with patient mortality and treatment outcome. RESULTS: In total, 79 MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0µg/mL in 53 episodes (67.1%). The presence of high vancomycin MIC was not associated with a higher mortality rate or treatment success. A daptomycin MIC≥0.5µg/mL was present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained and was associated with 30-day mortality in the multivariate analysis (odds ratio=4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used were associated with a lower risk of treatment failure or mortality. CONCLUSIONS: The pernicious effect of high vancomycin MIC disappears in the absence of a predominant use of this antibiotic. However, a high daptomycin MIC in MRSA bacteraemia is associated with higher mortality in patients with bacteraemia, irrespective of antimicrobial treatment choice.

Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in critically ill patients.

OBJECTIVES: This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients. METHODS: An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (Cmax) and minimum (Cmin) plasma concentration samples were taken during the first 48-96h after the beginning of treatment. The impact of Cmax/MIC ratio and area under the concentration-time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model. RESULTS: A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65. Clinical response at the end of treatment was significantly greater in patients with Cmax/MIC >6 [OR=5.48 (95% CI 1.28-11.40)], Cmax/MIC >8 [OR=6.01 (2.41-12.2)] and Cmax/MIC >10 [OR=8.02 (2.21-14.2)]. Cmax/MIC >10 was associated with a non-significant increase in microbiological eradication [OR=2.84 (0.76-10.61)]. Achieving Cmax/MIC >6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC curve 0.77 (0.66-0.87)]. CONCLUSIONS: The Cmax/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains.

Impact of an antimicrobial stewardship program on critical haematological patients.

OBJECTIVE: Antimicrobial Stewardship Programs (ASPs) have appeared as very useful tools in order to improve the use of antimicrobial agents. The objective of this study is to assess the impact of an ASP on haematological patients hospitalized in an Intensive Care Unit (ICU). METHODS: A quasi-experimental pre-post intervention study, which included haematological patients admitted to an ICU and assessed by the ASP program during 3 years. The impact of the program on patient evolution was assessed by comparison between the previous period and the intervention period in terms of mortality, mean stay, number of re-hospitalizations, and duration of mechanical ventilation for intubated patients. RESULTS: The ASP team assessed 324 antimicrobial agents in 169 patients; they recommended 121 modifications, including 55 treatment discontinuations. Compared with the pre-intervention period, there were no significant differences in the variables assessed. No variation was observed in colonization by multi-resistant bacteria. CONCLUSIONS: The implementation of an APS on critical haematological patients will lead to a relevant number of treatment modifications, without any impact on the clinical evolution of patients.

Introducción: Los programas de optimización de antimicrobianos (PROA) han surgido como herramientas de gran utilidad para mejorar el uso de estos. El objetivo del presente estudio es evaluar el impacto de un PROA sobre pacientes hematológicos ingresados en una unidad de pacientes críticos.Material y métodos: Estudio cuasi-experimental pre-post intervención. Se incluyeron pacientes hematológicos ingresados en una unidad de críticos evaluados por el equipo PROA durante 3 años. El impacto del programa sobre la evolución de los pacientes se evaluó mediante la comparación entre el periodo previo y de intervención de la mortalidad, estancia media, número de reingresos y duración de ventilación mecánica en los pacientes intubados.Resultados: 324 antimicrobianos de 169 pacientes fueron evaluaron por el equipo PROA, recomendando un total de 121 modificaciones, incluyendo 55 suspensiones de tratamiento. Comparados con el periodo pre-intervención, no se observaron diferencias significativas en las variables consideradas. No se observó variación en la colonización por bacterias multirresistentes.Conclusiones: La implantación de un PROA sobre el paciente crítico hematológico conduce a un número relevante de modificaciones en el tratamiento, sin afectar la evolución clínica de los pacientes.

Cost-effectiveness analysis of implementing an antimicrobial stewardship program in critical care units.

AIMS: To evaluate the cost-effectiveness of antimicrobial stewardship (AS) program implementation focused on critical care units based on assumptions for the Spanish setting. MATERIALS AND METHODS: A decision model comparing costs and outcomes of sepsis, community-acquired pneumonia, and nosocomial infections (including catheter-related bacteremia, urinary tract infection, and ventilator-associated pneumonia) in critical care units with or without an AS was designed. Model variables and costs, along with their distributions, were obtained from the literature. The study was performed from the Spanish National Health System (NHS) perspective, including only direct costs. The Incremental Cost-Effectiveness Ratio (ICER) was analysed regarding the ability of the program to reduce multi-drug resistant bacteria. Uncertainty in ICERs was evaluated with probabilistic sensitivity analyses. RESULTS: In the short-term, implementing an AS reduces the consumption of antimicrobials with a net benefit of €71,738. In the long-term, the maintenance of the program involves an additional cost to the system of €107,569. Cost per avoided resistance was €7,342, and cost-per-life-years gained (LYG) was €9,788. Results from the probabilistic sensitivity analysis showed that there was a more than 90% likelihood that an AS would be cost-effective at a level of €8,000 per LYG. LIMITATIONS: Wide variability of economic results obtained from the implementation of this type of AS program and short information on their impact on patient evolution and any resistance avoided. CONCLUSIONS: Implementing an AS focusing on critical care patients is a long-term cost-effective tool. Implementation costs are amortized by reducing antimicrobial consumption to prevent infection by multidrug-resistant pathogens.

[Native valve Aspergillus fumigatus endocarditis with blood culture positive and negative for galactomannan antigen. Case report and literature review]. / Endocarditis por Aspergillus fumigatus en válvula nativa con hemocultivo positivo y galactomanano negativo. Descripción de un caso y revisión de la literatura.

Native valve endocarditis caused by Aspergillus spp. is an uncommon disease with a high mortality rate. Generally, Aspergillus is isolated from affected valve in post-mortem or biopsy specimens. However, its isolation from blood cultures is exceedingly rare. We report a case of fungal endocarditis in a native mitral valve with the isolation of Aspergillus fumigatus both in valve vegetation and in blood culture bottles. The patient underwent valve replacement and antifungal treatment with voriconazole and caspofungin, but he died on post-operative day 45 with disseminated aspergillosis confirmed by necropsy. Paradoxically, galactomannan antigen detection in serum was negative. This is the third case of Aspergillus endocarditis with positive blood culture reported in the literature.

Endocarditis por Aspergillus fumigatus en válvula nativa con hemocultivo positivo y galactomanano negativo. Descripción de un caso y revisión de la literatura / Native valve Aspergillus fumigatus endocarditis with blood culture positive and negative for galactomannan antigen. Case report and literature review

La endocarditis infecciosa causada por Aspergillus es infrecuente y sepresenta en pacientes con cirugía cardiaca previa o en inmunodeficientes.Por lo general, el aislamiento del moho se realiza post-mortem, si bien elcultivo de la válvula o, en muy pocos casos, el hemocultivo permiten suaislamiento. Describimos un caso de endocarditis infecciosa por Aspergillusfumigatus sobre válvula nativa mitral, con aislamiento de Aspergillus en lavegetación valvular y en el hemocultivo. A pesar del recambio valvular y derecibir una terapia combinada con voriconazol y caspofungina, el pacientefalleció con aspergilosis diseminada confirmada en la necropsia. El presentesería el tercer caso descrito de endocarditis infecciosa por Aspergillus conhemocultivo positivo. Paradójicamente, la determinación del antígeno degalactomanano fue negativa(AU)

Native valve endocarditis caused by Aspergillus spp. is an uncommon diseasewith a high mortality rate. Generally, Aspergillus is isolated from affected valvein post-mortem or biopsy specimens. However, its isolation from bloodcultures is exceedingly rare. We report a case of fungal endocarditis in anative mitral valve with the isolation of Aspergillus fumigatus both in valvevegetation and in blood culture bottles. The patient underwent valvereplacement and antifungal treatment with voriconazole and caspofungin, buthe died on post-operative day 45 with disseminated aspergillosis confirmed bynecropsy. Paradoxically, galactomannan antigen detection in serum wasnegative. This is the third case of Aspergillus endocarditis with positive bloodculture reported in the literature(AU)

[Epidemiology of candidemia in Spain - Multicenter study] / Estudio multicéntrico sobre la epidemiología de las candidemias en España.

The results of the epidemiological study on candidemias with the highest number of cases carried out in Spain is presented. This study is included in the Epidemiological Survey of Candidemia in Europe supported by the ECMM in which another five countries take part. In the Spanish study, 19 hospitals participated, 290 candidemia episodes were analysed (80 in children under 15 years and 210 in adults), 293 strains of yeasts being isolated. Both in children and in adults, the risks factors more frequently observed were the intravenous catheter and previous antibiotic therapy. In adults, the most habitual underlying disease was the solid tumor and, in children, hematological diseases. Candida albicans was the most prevalent species isolated in adults (46.1%) and Candida parapsilosis in children (50%). As part of the therapy, the intravenous line was removed and antifungal treatment was prescribed to 74% and 92.5% of children, respectively and to 43.8% and 73.8% of adults. The antifungal agent of election in adults was fluconazole (54.8%) and liposomal amphotericin B (58.1%) in children. The global mortality of the study was 38.9%, which for ages was major in adults (41.4%) than in children (38.7%). The geographical distribution of the isolated species was homogeneous, C. albicans being the predominant species, with the exception of Galicia and Extremadura where C. parapsilosis was the most frequent.