Showing papers by "Mario Fernández-Ruiz published in 2019"

Executive summary of clinical practice guideline for the management of invasive diseases caused by Aspergillus: 2018 Update by the GEMICOMED-SEIMC/REIPI.

Abstract: Aspergillus infection is a significant cause of morbi-mortality in an at-risk population. The Study Group of Fungal Infections (GEMICOMED) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has reviewed announcements made in invasive aspergillosis management. We have organized our recommendations in such a way as to provide a guide in resolving different clinical situations concerning the entire spectrum of invasive diseases caused by Aspergillus in various populations. Diagnostic approach, treatment and preventions strategies are outlined. It is not our aim that these guidelines supplant clinical judgment with respect to specific patients; however, it is our objective to perform a comprehensive summary of quality of care evidence for invasive aspergillosis management in different settings.

Usefulness of guideline recommendations for prognosis in patients with candidemia

Abstract: We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.

Going beyond serology for stratifying the risk of CMV infection in transplant recipients.

Abstract: Knowledge of donor and recipient (D/R) cytomegalovirus (CMV) serostatus is critical for risk stratification of CMV infection and disease in transplant recipients, particularly in the solid organ transplantation (SOT) setting. Despite its broad availability and the success of it use, the risk stratification based on the D/R serostatus is not free of limitations since there are a nondepreciable number of patients that are not accurately categorized by this approach. In fact, up to 20% of seropositive SOT recipients, classically considered at intermediate risk, develop episodes of CMV infection and disease after transplantation. Here, we provide an overview of additional donor and recipient factors that may have utility in identifying patients at risk for post-transplant CMV infection. Specifically, we summarize our current understanding regarding the potential use of use CMV-specific T-cell-mediated immunity, neutralizing antibodies and host genetics that may influence the risk of CMV infection and disease. We provide an overview of the benefits and limitations associated with using these immunological factors in risk stratification and propose specific variables that could be analyzed at the pretransplant evaluation to improve the identification of patients with increased individual susceptibility.

Toxin B PCR Amplification Cycle Threshold Adds Little to Clinical Variables for Predicting Outcomes in Clostridium difficile Infection: a Retrospective Cohort Study.

Abstract: The objective of the present study was to evaluate the value of the PCR cycle threshold (CT) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of Clostridium difficile infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert C. difficile PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA (“EIA-including model”) or the optimal PCR CT cutoff value (“PCR-including model”) into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR CT was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; P = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; P = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the “PCR-including model” was similar to that for the “EIA-including model” (0.785 versus 0.775, respectively). The optimal PCR CT value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the “PCR-including model” was again similar to that of the “EIA-including model” (0.804 versus 0.801). Despite the inverse correlation between PCR CT and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA.

Candidemia in solid organ transplant recipients in Spain: Epidemiological trends and determinants of outcome.

Abstract: Background Despite being considered a high-risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized. Methods We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010-2011) and the CANDI-Bundle Study (2016-2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all-cause 7-day mortality and/or persistent candidemia for ≥72 hours) and 30-day mortality were investigated by univariate analysis. Results We included 55 episodes of post-transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non-susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30-day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03-0.85; P-value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03-0.76; P-value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02-0.89; P-value = .041) were protective for 30-day mortality. Conclusions High rates of non-albicans species and fluconazole non-susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia.

A short course of antibiotic treatment is safe after catheter withdrawal in catheter-related bloodstream infections due to coagulase-negative staphylococci.

Abstract: CoNS is the main cause of catheter-related bloodstream infections (CRBSI). Current guidelines recommend catheter withdrawal followed by antibiotics for at least 5 days. We aimed to assess the efficacy and safety of a shorter course of antibiotherapy in patients with CoNS CRBSI. All proven cases of CoNS CRBSI at our institution (Jan 12/Dec 17) were retrospectively analysed. Comparison of clinical characteristics and outcomes between patients receiving a short (SC ≤ 3 days) versus long antibiotic course (LC > 3 days) was performed. Cox regression models predicting the risk for complications (including propensity score [PS] for treatment assignment as covariate) were designed to adjust baseline differences among both treatment groups. A total of 79 cases were included. Most patients (75.9%) showed clinical response at day 7 after catheter removal. Complications occurred in 3.8% (three cases of septic thrombophlebitis) with no cases of endocarditis. Microbiological relapse (MR) occurred in 13 patients (16.5%). SC and LC were administered to 25 (31.6%) and 54 (68.4%) patients, respectively, with no significant differences in MR-free survival between SC and LC groups (87.8 vs 86.3%; P = 0.6). In PS-adjusted Cox regression analyses, a tunnelled catheter as the source of CRBSI was the only independent risk factor for MR (hazard ratio, 5.71; 95% confidence interval, 1.6–21) whereas the duration of therapy had no apparent impact. Shortening antibiotic therapy to ≤ 3 days is not associated with a poorer outcome or a greater risk of MR in patients with CoNS CRBI with catheter withdrawal.

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation.

Abstract: Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.

Recomendaciones GEMICOMED/GEIRAS-SEIMC para el manejo de las infecciones y colonizaciones por Candida auris

Abstract: Candida auris is a new species of Candida that causes nosocomial outbreaks in several countries around the world, including Spain. C.auris is resistant to fluconazole and multi- and pan-resistant strains have been described. It is highly transmissible and can survive long term in the hospital environment, causing long-lasting outbreaks that are difficult to detect in early stages, and making it difficult to control and eradicate. It is currently an emerging threat to global health. This document provides a set of guidelines, developed by a multidisciplinary team, to limit the impact and facilitate the control of C.auris infection based on the experiences gathered in the Spanish and English outbreaks. The implementation of early and strict surveillance and control measures is essential to prevent the spread of the outbreak, which can spread over time, posing a significant risk to complex, critical and immunocompromised surgical patients. Immediate notification of C.auris isolation to clinical and infection control teams, as well as to health authorities and institutions, is essential to implement infection control measures at all levels in a timely manner, to prevent internal and inter-centre transmission, and to ensure a proper surveillance and prevention to patients who are already colonized and can develop an infection.

Low 25-hydroxyvitamin D Levels and the Risk of Late CMV Infection After Kidney Transplantation: Role for CMV-specific Mediated Immunity.

Abstract: This work was supported by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III (Proyecto Integrado de Excelencia [PIE] 13/00045) and the Fundación Mutua Madrileña de Investigación Médica (FMM Grant 2014/0092). M.F.-R. is the recipient of a “Miguel Servet” research contract (CP 18/00073) from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III.

Risk Assessment of Infections in SOT Recipients

Abstract: The susceptibility to infection among solid organ transplant (SOT) recipients is modulated by a number of pre- and post-transplant variables that must be taken into account in the risk assessment process. Causative agents of post-transplant infection may be endogenous (reactivation of a chronic or latent infection), derived from the donor or the preservation fluid or acquired from an exogenous source (through environmental, vector, or human-to-human exposure). Overall, the latter group represents the most usual mechanism of infection among SOT recipients. Due to their frequent requirement for prolonged hospitalization, invasive diagnostic and therapeutic procedures, and broad-spectrum antibiotic therapy, healthcare-associated exposure is of particular concern. The present chapter will discuss how to evaluate the individual risk of infection in an individual SOT candidate or recipient. We will cover variables such as the timing from transplant, donor and surgical factors, the impact of antimicrobial prophylaxis and antirejection therapy, and the net state of immunosuppression. The changing nature of most of these variables should motivate a dynamic risk assessment throughout the entire post-transplant period. In addition, the different strategies currently available for post-transplant immune monitoring (either non-specific or specifically focused on a given pathogen, such as cytomegalovirus) will be reviewed.