[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Targeted prophylaxis has proven to be an efficient strategy in liver transplant recipients (LTR). OBJECTIVE: To compare the effectiveness and safety of caspofungin with that of fluconazole in high-risk LTR (HR-LTR). METHODS: Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR-LTR in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. RESULTS: During the study period (2005-2012), we analyzed 195 HR-LTR from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole Of a total of 17 global IFI (8.7%), breakthrough IFI accounted for 11 (5.6%) and invasive aspergillosis (IA) for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFI. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFI (2.1% vs 9.2%, p: 0.04). In patients requiring dialysis (n: 62), caspofungin significantly reduced the frequency of breakthrough IFI (p: 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction: 0.06; 95%CI: 0.001-0.11; p: 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. CONCLUSIONS: Caspofungin and fluconazole have similar efficacy for the prevention of global IFI in HR-LTR in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFI and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR-LTR, although bilirubin levels may be increased. This article is protected by copyright. All rights reserved.
No preview · Article · Dec 2015 · Liver Transplantation
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the usefulness of the secretion of interferon-γ (IFNγ) by cytomegalovirus (CMV)-specific CD8+ T cells to determine the risk of CMV reactivation in critically ill non-immunosuppressed patients.
Two-center prospective cohort study including critically ill non-immunosuppressed CMV-seropositive patients admitted between December 2012 and March 2013. The incidence of CMV reactivation by polymerase chain reaction (real-time PCR) in plasma was investigated. IFNγ secretion by CMV-specific CD8+ T lymphocytes was determined at the time of admission to the intensive care unit (ICU) by means of the QuantiFERON(®)-CMV (QF-CMV) test. Cox regression analyses were performed to investigate CMV reactivation risk factors.
Fifty-three patients were included, of whom 13 (24.5 %) presented CMV reactivation. Twenty-six patients (49.1 %) were QF-CMV "reactive" (QF-CMVR). Of the 26 QF-CMVR patients, 11.5 % (3/26) had CMV reactivation, whereas 37 % (10/27) of QF-CMV "non reactive" patients (QF-CMVNR) presented reactivation (p = 0.03). By Cox regression, the presence of QF-CMVR at ICU admission (HR 0.09, 95 % CI 0.02-0.44; p = 0.003) was associated with a decreased risk of CMV reactivation. The sensitivity, specificity, positive predictive value, and negative predictive value of QF-CMV were 77, 57, 37, and 88 %, respectively. Eleven of the 53 patients (20.7 %) died during the follow-up period. Mortality was more frequent in patients with CMV reactivation (6/13, 46.1 vs. 5/40, 12.5 %; p = 0.015).
In critically ill non-immunosuppressed patients, the presence of functional CMV-specific CD8+ T lymphocyte response at intensive care unit admission provides protection against CMV reactivation.
No preview · Article · Nov 2015 · Intensive Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Conclusions:
HIV infection had no impact on recurrence of HCC or survival after LT. Our results support the indication of LT in HIV-infected patients with HCC. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background:
The influence of cytomegalovirus (CMV) on recurrent hepatitis C virus (HCV) in liver grafts is controversial. Our aim was to investigate the association between CMV infection and disease and severe HCV recurrence (composite variable of presence of stage 3 to 4 fibrosis, need for retransplantation or death due to liver disease) in the first year after transplantation.
An observational, prospective, multicenter study was performed. The CMV replication was monitored by determining CMV viral load weekly during hospitalization after transplantation, twice monthly in the first 3 months after discharge, and at each follow-up visit until month 12. Liver fibrosis was assessed histologically by liver biopsy or transient elastometry. Pretransplant, intraoperative, and posttransplant variables were recorded. Multiple logistic regression was performed to study the impact of CMV on severe HCV recurrence.
Ninety-eight patients were included. The CMV infection was detected in 48 patients (49%) in the first year posttransplant, of which 11 patients (22.9%) had CMV disease. Twenty-three patients (23.5%) had severe HCV recurrence. Of these, 17 (73.9%) developed stage 3 to 4 fibrosis, 4 (17.4%) died, and 2 (8.7%) underwent retransplantation. Only 7 of 12 (58.3%) seronegative recipients of a seropositive donor (positive donor/negative recipient [D+/R-]) received universal prophylaxis, and 10 of 12 (83.3%) D+/R- patients developed CMV replication. In the multivariate analysis, the presence of CMV D+/R- serodiscordance (odds ratio, 6.87; 95% confidence interval, 1.89-24.99; P = 0.003), and detection of a higher peak HCV viral load (odds ratio, 3.85; 95% confidence interval, 1.49-9.94; P = 0.005) were associated with severe HCV recurrence.
Our results support an association between CMV D+/R- serodiscordance and severe HCV recurrence in patients undergoing liver transplantation for HCV liver disease.
[Show abstract][Hide abstract] ABSTRACT: Objective:
A prospective analysis of the distribution of NK subsets and natural cytotoxicity receptors (NKp30/NKp46) in HIV patients with long-term HAART use and sustained virological and immunological response.
The main inclusion criteria were: at least 3 years' receipt of HAART; current CD4+ count ≥ 500 cells/mm3; undetectable viral load for at least 24 months; no hepatotropic virus co-infection. Percentages of CD56dim, CD56bright NK cells and CD56neg CD16+ cells were obtained. Expression of the NCRs, NKp30 and NKp46 was analysed in CD56+ cells. Thirty-nine infected patients and sixteen healthy donors were included in the study.
The percentages of total CD56+ and CD56dim NK cells were significantly lower in HIV-infected patients than in healthy donors (70.4 vs. 50.3 and 80.9 vs. 66.1 respectively). The percentage of total CD56+ NK cells expressing NCR receptors was lower in HIV patients than in healthy donors (NKp30: 25.20 vs. 58.63; NKp46: 24.8 vs. 50.59). This was also observed for CD56dim and CD56bright NK cells. Length of time with undetectable HIV viral load was identified as an independent factor associated with higher expression of NKp30 and NKp46.
Despite the prolonged and effective use of HAART, HIV-infected patients do not fully reconstitute the distribution of NK cells. Length of time with an undetectable viral load was related to greater recovery of NKp30/NKp46 receptors.
[Show abstract][Hide abstract] ABSTRACT: Background:
It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver transplant recipients. This study was designed to investigate the efficacy and safety of levofloxacin.
An open-label, prospective, multicenter, randomized study was conducted to compare the efficacy and safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and isoniazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was measured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication were recorded.
CONSORT guidelines were followed in order to present the results. The safety committee suspended the study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levofloxacin arm). The reason for suspension was an unexpected incidence of severe tenosynovitis in the levofloxacin arm (18.2%). Although the clinical course was favorable in all cases, tenosynovitis persisted for 7 weeks in some patients. No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31) and 54.5% of patients randomized to levofloxacin (18/33, P = .094) completed prophylaxis. No patient developed tuberculosis during the study follow-up (median 270 days).
Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.
Full-text · Article · Feb 2015 · Clinical Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND & AIM
The seroprevalence of the hepatitis E virus (HEV) and its chronicity rate in the HIV-infected population has not been well established. As a result, the magnitude of this emerging disease in this population cannot be established.
Prospective study that included HIV-infected patients followed up between September 2012 and May 2013. All included patients were tested for anti-HEV IgG/IgM. In patients with confirmed anti-HEV IgG/IgM positivity, RT-PCR was performed. In patients where HEV RNA was amplified, a second RT-PCR assay was performed 6 months later to identify transient or chronic HEV infections.
Eight hundred and ninety-four HIV-infected patients were enrolled in the study. Of these patients, 399 (44.6%) were monoinfected with HIV; 462 (51.6%) were co-infected with HIV/HCV; 12 (1.3%) were co-infected with HIV/HBV; and 21 (2.3%) were co-infected with HIV/HCV/HBV. In 88 patients, anti-HEV IgG/IgM was detected (seroprevalence: 9.8% [95% CI: 8.02%-11.9%]). In five patients (0.5%; 95% CI: 0.2%-1.2%), HEV RNA was detected; 5.7% (95% CI: 2.1%-12.1%) of the patients were anti-HEV IgG/IgM positive. None of these patients showed detectable HEV RNA six months later.
HEV infection is frequent in HIV-infected patients but developing a chronic HEV infection may be considered an uncommon liver disease in this population.
No preview · Article · Nov 2014 · Journal of Infection
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Antimicrobial therapy for sepsis caused by carbapenem- and colistin-resistant Klebsiella pneumoniae is not well established. We hypothesized that the early use of gentamicin in cases due to susceptible organisms would decrease the crude mortality rate of this infection.
This retrospective cohort study examined 50 cases of sepsis caused by carbapenem-resistant K. pneumoniae occurring between June 2012 and February 2013 during an outbreak of K. pneumoniae ST512 producing KPC-3, SHV-11 and TEM-1. Survival curves categorized by the use of gentamicin were constructed using the Kaplan-Meier method and compared using the log-rank test. Eight multivariate models using Cox regression were designed to study the risk factors for mortality and test the hypothesis.
The 30 day crude mortality rate was 38%. The use of targeted gentamicin was associated with reduced mortality (20.7% versus 61.9%, P = 0.02). In all multivariate regression models, the use of gentamicin was independently associated with lower mortality until Day 30 (HR 0.17-0.29, P = 0.03-0.002 depending on the model) after controlling for other potential confounding variables such as age, optimal treatment, renal function, severity of infection, underlying disease, use of tigecycline and previous hospitalization.
Gentamicin reduced the mortality from sepsis caused by this K. pneumoniae ST512 clone producing KPC-3, SHV-11 and TEM-1.
No preview · Article · Oct 2014 · Journal of Antimicrobial Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Despite administration of annual influenza vaccination, influenza-associated complications in transplant recipients continue to be an important cause of hospitalization and death. Although influenza vaccination has been proven to be the most effective measure to reduce influenza infection after transplantation, transplant recipients are still vulnerable to influenza infections, with lower serological responses to vaccination compared to the general population. In order to assess the efficacy and safety of an alternative immunization scheme for solid organ transplant recipients, the TRANSGRIPE1-2 Study Group aimed to test a booster dose administration 5 weeks after the standard vaccination. The primary objective of this trial was to compare short-term and long-term neutralizing antibody immunogenicity of a booster dose of influenza vaccination to the standard single-dose immunization scheme. Secondary objectives included the evaluation of the efficacy and/or safety, cellular immune response, incidence of influenza infection, graft rejection, retransplant and mortality rates.
This phase III, randomized, controlled, open-label clinical trial was conducted between October 2012 and December 2013 in 12 Spanish public referral hospitals. Solid organ transplant recipients (liver, kidney, heart or lung), older than 16 years of age more than 30 days after transplantation were eligible to participate. Patients (N = 514) were stratified 1:1 by center, type of organ and time after transplantation and who either received the standard single dose (n = 257) or were treated according to a novel influenza vaccination schedule comprising the administration of a booster dose 5 weeks after standard vaccination (n = 254). Seroconversion rates were measured as a determinant of protection against influenza (main outcome). Efficacy and safety outcomes were followed until 1 year after influenza vaccination with assessment of short-term (0, 5, 10 and 15 weeks) and long-term (12 months) results. Intention-to-treat, per-protocol and safety analyses will be performed.
This trial will increase knowledge about the safety and efficacy of a booster dose of influenza vaccine in solid organ transplant recipients. At the time the manuscript was submitted for publication, trial recruitment was closed with a total of 499 participants included during a 2-month period (within the seasonal influenza vaccination campaign).
ClinicalTrials.gov Identifier: NCT01761435 (registered 13 December 2012).
EudraCT Identifier: 2011-003243-21 (registered 4 July 2011).
[Show abstract][Hide abstract] ABSTRACT: Background
Optimizing HCV genotype 1 therapy in terms of response prediction and tailoring treatment is undoubtedly the cornerstone of treating HIV co-infected patients in clinical practice. Accordingly, our aim was to analyze the predictive value of HCV viral decline for sustained virological response (SVR), measured at a time point as early as week 2 of therapy with pegylated interferon alpha-2a plus ribavirin (Peg-IFN/RBV).
Previously untreated HIV/HCV genotype 1 co-infected patients were included in this study. The HCV RNA titer was measured at week 2 after starting treatment with Peg-IFN/RBV. The likelihood of reaching SVR when HCV RNA viral titers declined at week 2 was evaluated relative to predictive baseline factors.
A total of 192 HIV/HCV genotype-1 co-infected patients were enrolled in the study and began therapy. One hundred and sixty-three patients completed a full course of Peg-IFN/RBV treatment for 2 weeks and 59 of these (36.2%) reached SVR. An HCV RNA viral load decline of ≥1.5 log IU/mL at week 2 had the maximum positive predictive value for SVR (83.3%; 95% CI: 68.5%–92.9%) and was identified as the strongest independent predictive factor for reaching SVR across all baseline predictive factors.
HCV viral decline at week 2 had a high predictive value for identifying patients with a high and low likelihood of reaching SVR using dual therapy, regardless of strong predictive baseline factors. This finding may be useful for developing a predictive tool to help tailor HCV genotype 1 therapy in HIV co-infected patients.
[Show abstract][Hide abstract] ABSTRACT: We determined the characteristics of posttransplant tuberculosis and the impact of rifampin-based antituberculosis regimens on outcomes in the current era. Patients comprised 64 transplant recipients with tuberculosis, divided into 2 consecutive cohorts: an earlier cohort (cases occurring from 2003 to 2007) and a later cohort (cases from 2008 to 2011). Patients from the later versus earlier era had tuberculosis develop later after transplant (odds ratio, 1.01; 95% CI, 1.00-1.02; P= .05), were more likely to be liver transplant recipients (odds ratio, 4.52; 95% CI, 1.32-15.53; P= .02), and were more likely to receive tacrolimus-based immunosuppression (odds ratio, 3.24; 95% CI, 1.14-9.19; P= .03). Mortality rate was 10% in the later cohort and 21% in the earlier cohort (P= .20). Rifampin-based treatment was less likely to be used in patients with prior rejection (P= .04). However, neither rejection rate (P= .71) nor mortality (P= .93) after tuberculosis differed between recipients who received rifampin and recipients who did not. Thus, notable changes have occurred in the epidemiological characteristics of tuberculosis in transplant recipients. Overall mortality rate has improved, with about 90% of the patients now surviving after tuberculosis.
No preview · Article · Mar 2014 · Progress in transplantation (Aliso Viejo, Calif.)
[Show abstract][Hide abstract] ABSTRACT: It is not known whether the probability of achieving sustained virological response (SVR) can be determined on the basis of the magnitude of HCV viral decline over the first 4 weeks of Peg-IFN/RBV treatment of HIV/HCV co-infected patients who fail to achieve a rapid virological response (RVR).
HIV patients co-infected with HCV genotype 1 naïve to Peg-IFN/RBV treatment were included. HCV viral decline from baseline to week 4 was graded. The positive predictive value (PPV) for SVR was evaluated according to the magnitude of HCV viral decline at week 4.
One hundred and fifty patients were included. Thirty-four (22.6%) patients achieved RVR, 33 of these (PPV [CI 95%]; 97.05% [86.34-99.85]) achieved SVR. In those patients who did not achieve RVR, the probability to achieving SVR was graded according to the magnitude of viral decline at week 4 (>2 log10 [55.5%], >2.5 log10 [73.3%] and >3 log10 [75%]). The combination of undetectable and magnitude of decline (>2.5 log10) had a PPV for SVR of 89.8% (CI 95%; 0.794-0.964).
The combination of undetectable HCV viral load andmagnitude of decline at week 4 has a high PPV for SVR and identified ahigher number of potential Peg-IFN/RBV responders.
Full-text · Article · Nov 2013 · The Journal of infection