[Show abstract][Hide abstract] ABSTRACT: Background
Invasive candidiasis (IC) is a frequent and life-threatening infection in critically ill patients. The aim of this study was to evaluate the epidemiology of IC and the antifungal susceptibility of etiological agents in patients admitted to our surgical intensive care unit (SICU) in Spain.
We designed a prospective, observational, single center, population-based study in a SICU. We included all consecutive adult patients (≥18 years old) who had documented IC, either on admission or during their stay, between January 2012 and December 2013.
There were a total of 22 episodes of IC in the 1149 patients admitted during the 24-month study. The overall IC incidence was 19.1 cases per 1000 admissions. Thirteen cases of IC (59.1 %) were intra-abdominal candidiasis (IAC) and 9 (40.9 %) were candidemias. All cases of IAC were patients with secondary peritonitis and severe sepsis or septic shock. The overall crude mortality rate was 13.6 %; while, it was 33 % in patients with candidemia. All patients with IAC survived, including one patient with concomitant candidemia. The most common species causing IC was Candida albicans (13; 59.1 %) followed by Candida parapsilosis (5; 22.7 %), and Candida glabrata (2; 9.1 %). There was also one case each (4.5 %) of Candida krusei and Candida tropicalis. Thus, the ratio of non-C. albicans (9) to C. albicans (13) was 1:1.4. There was resistance to fluconazole and itraconazole in 13.6 % of cases. Resistance to other antifungals was uncommon.
Candida parapsilosis was the second most common species after C. albicans, indicating the high prevalence of non-C. albicans species in the SICU. Resistance to azoles, particularly fluconazole, should be considered when starting an empirical treatment. Although IAC is a very frequent form of IC in critically ill surgical patients, prompt antifungal therapy and adequate source control appears to lead to a good outcome. However, our results are closely related to our ICU and any generalization must be taken with caution. Therefore, further investigations are needed.
BMC Research Notes 09/2015; 8(1). DOI:10.1186/s13104-015-1458-4
[Show abstract][Hide abstract] ABSTRACT: A bidirectional interaction between active cytomegalovirus (CMV) infection and acute graft versus host disease (aGvHD) is pathogenetically feasible given the pro-inflammatory nature of CMV and the immunosuppressive effect directly attributable to aGvHD . Contradictory data have been published on this issue [2-5]. The use of methods for CMV surveillance displaying different sensitivities (pp65 antigenemia assay-AG- vs. real-time PCR assays) may account in part for these discrepancies . In this single-center retrospective study we reexamined this potential association using highly sensitive real-time PCR assays (limit of detection: approximately 20 copies/ml-[6-8]) (CMV PCR Kit and the New CMV RealTime PCR assay; Abbott Molecular, Des Plaines, IL) in plasma specimens. We included 92 non-consecutive patients undergoing Allo-SCT (January 2010-August 2014) for hematological malignancy. This article is protected by copyright. All rights reserved.
Transplant International 09/2015; DOI:10.1111/tri.12689 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolomics analysis of biofluids is being increasingly recognized as a useful tool for the diagnosis and management of a number of infectious diseases. Here we showed that plasma metabolomics profiling by untargeted 1H nuclear magnetic resonance may allow the anticipation of the occurrence of CMV DNAemia in allogeneic stem cell transplant (Allo-SCT). For this purpose, key discriminatory metabolites were total glutathione, taurine, methylamine, trimethylamine N-oxide and lactate, all of which were upregulated in patients eventually developing CMV DNAemia. The overall classification accuracy (predictability) of the projection to latent structure discriminant analysis (PLS-DA) model in cross-validation technical replicates was 73%. Increased levels of alanine, lactate and total fatty acids, and a shift in the fatty acid profile towards unsaturated species were observed in patients with detectable CMV DNA in plasma. The classification accuracy of this PLS-DA model in cross-validation technical replicates was 81%. Plasma metabolomics profiling may prove useful for identifying patients at highest risk for CMV DNAemia thus allowing early inception of antiviral therapy.
Journal of General Virology 09/2015; DOI:10.1099/jgv.0.000275 · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease.
A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis.
A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93% respectively).
The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: The role cytomegalovirus (CMV)-specific polyfunctional CD8+ T cells and that of antibodies neutralizing virus epithelial infection (AbNEI) in the control of CMV DNAemia was investigated in 39 CMV-seropositive allogeneic stem cell transplant recipients (Allo-SCT) with (n=24) or without (n=15) CMV DNAemia. AbNEI levels were prospectively monitored by means of a neutralization assay employing retinal epithelial cells (ARPE-19) and the recombinant CMV strain BADrUL131-Y4. Quantification of CMV-specific polyfunctional CD8+ T cells (expressing 2 or 3 of the following markers: IFN-γ, TNF-α, CD107a) in whole blood was performed by flow cytometry for intracellular cytokine staining. We found no differences in the dynamic pattern of AbNEI in patients with or without subsequent CMV DNAemia. Baseline and peak AbNEI titers were not predictive of the dynamics of CMV replication within episodes. No correlation was found between CMV DNA loads and AbNEI levels during episodes of CMV DNAemia (rho=0.09; 95% C.I. -0.52-0.64; P=0.78). The detection of pp65/IE-1 CMV-specific polyfunctional CD8+ T cells was associated with low level viral replication within subsequent episodes of CMV DNAemia. Interestingly, the presence of AbNEI titers (inverse) >4.7 log2 was predictive of the occurrence of CMV DNAemia (sensitivity, 83%; Specificity, 80%). Our findings should add insights to the role of humoral and cellular immunity in the control of CMV infection in the Allo-SCT setting.
Journal of General Virology 05/2015; 96(9). DOI:10.1099/vir.0.000203 · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The functional profile of cytomegalovirus (CMV)-specific CD8(+) T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized.
We enumerated pp65 and immediate early (IE)-1-specific CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT.
Fifty out of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did (P = 0.04). Qualitatively, no major differences in the functional signature of CMV-specific CD8(+) T cells were noted between patients who had or did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T cells at day +30 >0.30 cell/μL had a lower risk of CMV DNAemia (positive predictive value 76%, and negative predictive value 43%).
The presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was associated with lower levels of CMV replication, and higher frequency of self-resolved episodes. The data reported further clarify the role of polyfunctional CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease (PS-adjusted HR [aHR]: 0.10; 95% confidence interval [CI]: 0.01-0.79) and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Transplant International 04/2015; 28(9). DOI:10.1111/tri.12586 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A significant progress has been made in deciphering critical aspects of the biology and immunology of CMV infection in the allogeneic stem cell transplantation setting. Genetic traits predisposing to active CMV infection and CMV end-organ disease have begun to be delineated. Reliable molecular assays for CMV DNA load quantitation in body fluids have been developed. Elucidation of immune mechanisms affording control of CMV infection will help to improve the management of active CMV infection. Finally, the advent of new CMV-specific antivirals and promising vaccine prototypes as well as the development of fine procedures for large-scale ex vivo generation of functional CMV-specific T cells for adoptive T cell transfer therapies will certainly minimize the negative impact of CMV on survival in these patients.
[Show abstract][Hide abstract] ABSTRACT: It is uncertain whether monitoring plasma ganciclovir (GCV) levels is useful in predicting cytomegalovirus (CMV) DNAemia clearance
in preemptively treated allogeneic stem cell transplant recipients. In this observational study, including 13 episodes of
CMV DNAemia treated with intravenous (i.v.) GCV or oral valganciclovir, we showed that monitoring trough plasma GCV levels
does not reliably predict response to therapy. Rather, immunological monitoring (pp65 and immediate-early [IE]-1-specific
gamma interferon [IFN-γ]-producing CD8+ T cells) appeared to perform better for this purpose.