-
Oscar Len,
Dolores Rodríguez-Pardo,
Joan Gavaldà,
José María Aguado, Marino Blanes,
Nuria Borrell,
Germán Bou,
Jordi Carratalà,
José Miguel Cisneros,
Jesús Fortún,
Mercé Gurguí,
Miguel Montejo,
Carlos Cervera,
Patricia Muñoz,
Angel Asensio,
Julián Torre-Cisneros,
Albert Pahissa
[show abstract]
[hide abstract]
ABSTRACT: Clostridium difficile-associated disease (CDAD) is the most common cause of nosocomial diarrhea. Information about CDAD in solid organ transplant (SOT) recipients is scarce. To determine its epidemiology and risk factors, we conducted a cohort study in which 4472 SOT patients were prospectively included in the RESITRA/REIPI (Spanish Research Network for the Study of Infection in Transplantation) database between July 2003 and July 2006. Forty-two episodes of CDAD were diagnosed in 36 patients. The overall incidence was 0.94%. Median onset of infection was 31.5 days (range 6-741); in half the cases, onset occurred during the first month after transplantation. In 26% of cases, there was no previous antibiotic use. Independent risk factors for CDAD using Cox regression analysis were previous use of first- and second-generation cephalosporins (HR 3.68; 95%CI 1.8-7.52; P < 0.001), ganciclovir prophylactic use (HR 3.09; 95%CI 1.44-6.62; P = 0.004) and corticosteroid use before transplantation (HR 2.95; 95%CI 1.1-7.9; P = 0.031). There were no deaths related to CDAD. In summary, the incidence of CDAD in SOT was low, most cases were diagnosed soon after transplantation and the prognosis was good.
Transplant International 10/2012; · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: With the advent of highly active antiretroviral therapy in 1996, patients infected with HIV are now living longer and are dying from illnesses other than acquired immunodeficiency syndrome (AIDS). Liver disease due to chronic hepatitis C is now a leading cause of mortality among HIV-infected patients in the developed world. The prevalence of end-stage kidney or heart disease is also increasing among HIV-infected patients. For these patients, solid organ transplantation (SOT) is the only therapeutic option and HIV infection alone is not a contraindication. Accumulated experience in North America and Europe in the last few years indicates that 3- to 5-year survival in liver recipients coinfected with HIV and HCV is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected liver recipients and kidney recipients was similar to that of HIV-negative patients. Infections in the post-transplant period in HIV-infected recipients are similar to those seen in HIV-negative patients, although the incidence of some of them (e.g. tuberculosis and fungal infections) is higher. In the USA and Europe the number of immigrants from areas with endemic geographically-restricted infections has increased significantly in recent years. These changes in the population profile have led to an increase in the percentage of foreign-born transplant candidates and donors. Organ transplant recipients may develop endemic diseases in four ways: Transmission through the graft; de novo infection; reactivation of dormant infection; and reinfection/reactivation in a healthy graft. In foreign-born recipients, there is the possibility of endemic infections manifesting in the post-transplant period as a consequence of immunosuppression. These issues are modifying the criteria for donor selection and have also expanded pre-transplant screening for infectious diseases in both donors and transplant recipients. Some infectious diseases such as Chagas disease, endemic fungal infections, tuberculosis (which could be multidrug- or extensively drug-resistant according the origin of the recipient), leishmaniasis and other viral and parasitic diseases should always be considered in the differential diagnosis of post-transplant infections in foreign-born recipients.
Enfermedades Infecciosas y Microbiología Clínica 03/2012; 30 Suppl 2:76-85. · 1.49 Impact Factor
-
Asunción Moreno,
Carlos Cervera,
Jesús Fortún, Marino Blanes,
Estibalitz Montejo,
Manuel Abradelo,
Oscar Len,
Antonio Rafecas,
Pilar Martín-Davila,
Julián Torre-Cisneros,
Magdalena Salcedo,
Elisa Cordero,
Ricardo Lozano,
Iñaki Pérez,
Antonio Rimola,
José M Miró
[show abstract]
[hide abstract]
ABSTRACT: Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.
Liver Transplantation 09/2011; 18(1):70-81. · 3.39 Impact Factor
-
Rafael San-Juan,
Jose M. Aguado,
Carlos Lumbreras,
Jesus Fortun,
Oscar Len,
Patricia Munoz,
Miguel Montejo,
Asunción Moreno,
Elisa Cordero, Marino Blanes,
Antonio Ramos,
Julian Torre-Cisneros,
Francisco López-Medrano,
Jordi Carratala,
Enrique Moreno
[show abstract]
[hide abstract]
ABSTRACT: The role of selective intestinal decontamination with fluoroquinolones (FQ-SID) in the prevention of early bacterial infections (EBIs) in liver transplant recipients (LTRs) is unknown. We used the online database of the Spanish Network of Infection in Transplantation/Spanish Network for Research in Infectious Diseases, which prospectively analyzed 1010 LTRs from 12 Spanish hospitals from September 2003 to February 2005. We compared the incidence and etiology of EBIs (30 days after transplantation) in 415 LTRs from 4 centers that used FQ-SID (>7 days) and in 595 LTRs from 8 hospitals that did not use FQ-SID. A multivariate logistic regression analysis (including an adjustment for the transplant center factor) was performed to evaluate the potential protective factor of FQ-SID in the development of EBIs. We reported 266 EBI episodes in 252 LTRs (incidence = 24.9%). There were no differences in the incidence of EBIs between patients in the FQ-SID group and patients not in the FQ-SID group [109/415 (26.3%) versus 143/595 (24%), P = 0.9]. Although LTRs who received FQ-SID had a lower incidence of infections due to enteric bacteria (2.7% versus 6.5%, P = 0.007) and a higher incidence of infections due to nonfermenting gram-negative bacilli (6.6% versus 2.6%, P = 0.004), these findings could not be confirmed after an adjustment by the center factor in the multivariate models. We found no significant differences in the incidence of enterococcal infections (3.4% with FQ-SID versus 3.9% without FQ-SID, P = 0.5). Multivariate analysis did not confirm any protective effect of FQ-SID against the development of EBIs by enteric bacteria. In conclusion, FQ-SID does not reduce the incidence of EBIs in LTRs and could be withheld from this group of patients. Liver Transpl 17:896–904, 2011. © 2011 AASLD.
Liver Transplantation 07/2011; 17(8):896 - 904. · 3.39 Impact Factor
-
Rafael San-Juan,
Jose M Aguado,
Carlos Lumbreras,
Jesus Fortun,
Oscar Len,
Patricia Muñoz,
Miguel Montejo,
Asuncion Moreno,
Elisa Cordero, Marino Blanes,
Antonio Ramos,
Julian de la Torre-Cisneros,
Francisco Lopez-Medrano,
Jordi Carratala,
Enrique Moreno
[show abstract]
[hide abstract]
ABSTRACT: Although antifungal prophylaxis in high-risk liver transplant recipients (LTR) seems to be clearly justified, the efficacy of universal prophylaxis (UP) including low-risk patients is controversial.
From the study cohort RESITRA-REIPI, which prospectively analyzed 1010 LTR (September 2003 to February 2005) in 12 Spanish hospitals, we compared the incidence of early invasive fungal infection (IFI, first 90 days) between centers performing or not UP with fluconazole (for a minimum of 7 days) in low-risk LTR (none of the following: posttransplant renal failure, urgent transplant/retransplant, or choledochojejunostomy).
Three of 12 centers used UP. A total of 799 LTR were considered as low-risk patients (206 included in the UP group and 593 did not). We reported a total of 11 episodes of early IFI (six due to Candida albicans, one due to C. guillermondii, and three due to Aspergillus fumigatus) in 10 patients (incidence: 1.2%), with two cases of death attributable to IFI (18%) in both patients with invasive aspergillosis. There were no differences in the incidence of IFI between the patients receiving or not UP (4/206:1.9% vs. 6/593:1%, respectively; P=0.36).
IFI is infrequent in LTR not fulfilling major high-risk factors criteria, and prophylaxis with fluconazole in this low-risk group does not seem to be justified.
Transplantation 06/2011; 92(3):346-50. · 4.00 Impact Factor
-
Núria Fernàndez-Sabé,
Carlos Cervera,
Francisco López-Medrano,
Miguel Llano,
Elena Sáez,
Oscar Len,
Jesús Fortún, Marino Blanes,
Rosa Laporta,
Julián Torre-Cisneros,
Joan Gavaldà,
Patricia Muñoz,
M Carmen Fariñas,
José María Aguado,
Asunción Moreno,
Jordi Carratalà
[show abstract]
[hide abstract]
ABSTRACT: Solid-organ transplant (SOT) recipients are classically considered to be at increased risk for listeriosis. However, risk factors for this infection have not been assessed.
We carried out a multicenter, matched case-control study (1:2 ratio) from January 1995 through December 2007. Control subjects were matched for center, transplant type, and timing. Conditional logistic regression was performed to identify independent risk factors. Clinical features and outcomes for all case patients were reviewed.
Thirty patients (0.12%) with cases of listeriosis were identified among 25,997 SOT recipients at 15 Spanish transplant centers. In a comparison of case patients with 60 matched control subjects, the following independent risk factors for listeriosis were identified: diabetes mellitus (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.6-19.6; ), P = .007 history of cytomegalovirus infection or disease within the preceding 6 months (OR, 35.9; 95% CI, 2.1-620; P = .014), receipt of high-dose prednisone within the preceding 6 months (OR, 6.2; 95% CI, 1.8-21.1; P = .003), and trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (OR, 0.07; 95% CI, 0.006-0.76; P = .029). Twenty-six patients (86.7%) had bacteremia, and 7 had shock at presentation. Other manifestations included meningoencephalitis (10 cases), spontaneous peritonitis (2), pleural empyema (1), brain abscesses (1), and liver abscesses (1). The 30-day mortality rate was 26.7% (8 of 30 patients died).
Listeriosis in SOT recipients is uncommon but causes high mortality. Diabetes mellitus, cytomegalovirus infection or disease, and receipt of high-dose steroids are independent risk factors for this infection, whereas TMP-SMZ prophylaxis is a protective factor.
Clinical Infectious Diseases 10/2009; 49(8):1153-9. · 9.15 Impact Factor
-
Julián Torre-Cisneros,
Antonio Doblas,
José María Aguado,
Rafael San Juan, Marino Blanes,
Miguel Montejo,
Carlos Cervera,
Oscar Len,
Jordi Carratala,
José Miguel Cisneros,
Germán Bou,
Patricia Muñoz,
Antonio Ramos,
Merce Gurgui,
Nuria Borrell,
Jesus Fortún,
Asunción Moreno,
Joan Gavalda
[show abstract]
[hide abstract]
ABSTRACT: It is necessary to clarify the incidence of and risk factors for tuberculosis (TB) among solid-organ transplant (SOT) recipients as well as changes in the chronology, clinical presentation, and prognosis of the disease.
A total of 4388 SOT recipients were monitored prospectively at 16 transplant centers included in the Spanish Network for Research in Infectious Diseases (REIPI). TB episodes were studied, and the incidence rate was calculated. Certain variables were analyzed, by Cox regression analysis, as potential risk factors for TB.
Among the 4388 SOT recipients, 21 cases of TB were reported (0.48%). The median duration of follow-up was 360 days (range, 0-720 days). The global incidence of TB was 512 cases per 10(5) patients per year (95% confidence interval [CI], 317-783), which was higher than that in the general population in Spain (18.9 cases per 10(5) inhabitants per year; relative risk [RR], 26.6). The highest incidence (2072 cases per 10(5) patients per year; 95% CI, 565-5306) was observed among lung transplant recipients (RR, 73.3). Of the TB cases, 95% occurred within the first year after transplant, and 76% were pulmonary forms. Crude mortality was 19.0%, and attributable mortality was 9.5%. Multivariate analysis identified recipient age (RR, 1.05; 95% CI, 1.0-1.1) and receipt of a lung transplant (RR, 5.6; 95%, 1.9-16.9) as independent risk factors.
TB incidence is increased among SOT recipients. The risk factors identified were age and receipt of a lung transplant. TB-attributable mortality (9.5%) is still high.
Clinical Infectious Diseases 06/2009; 48(12):1657-65. · 9.15 Impact Factor
-
Jesus Fortún,
Pilar Martín-Dávila,
Miguel Montejo,
Patricia Muñoz,
José M Cisneros,
Antonio Ramos,
Cesar Aragón, Marino Blanes,
Rafael San Juan,
Joan Gavaldá,
Pedro Llinares
[show abstract]
[hide abstract]
ABSTRACT: The aim of this prospective, multicenter, noncomparative, open-label trial was to evaluate the prophylactic use of caspofungin in adult liver transplant recipients at high risk of developing invasive fungal infections (IFI).
Patients received caspofungin for at least 21 days. A successful treatment outcome was defined as the absence of breakthrough IFI during the first 100 days after the onset of caspofungin.
According to study design, 71 patients were included. In the modified intention-to-treat analysis, successful treatment outcome was obtained in 88.7%. Two patients developed IFI: a Mucor and a Candida albicans surgical wound infections, respectively. Six more patients discontinued caspofungin because of drug-related altered liver function. No clinical side effects were related to caspofungin. Altered analytical data compatible with grade IV toxicity, irrespective of caspofungin attribution, were observed in 27.7% of patients at the end of caspofungin prophylaxis and in 15.4% of patients in safety visit (14 days after ending caspofungin administration) (P=0.13). Eight patients died, six during caspofungin administration and two during follow-up period, but none were attributed to IFI or caspofungin toxicity.
These results show that caspofungin could be considered an efficacious and well-tolerated drug as antifungal prophylaxis in high-risk liver transplant recipients.
Transplantation 03/2009; 87(3):424-35. · 4.00 Impact Factor
-
Rafael San Juan,
José Maria Aguado,
Carlos Lumbreras,
Jesus Fortun,
Patricia Muñoz,
Joan Gavalda,
Francisco Lopez-Medrano,
Miguel Montejo,
German Bou, Marino Blanes,
Antonio Ramos,
Asuncion Moreno,
Julian Torre-Cisneros,
Jorge Carratalá
[show abstract]
[hide abstract]
ABSTRACT: Current advances in transplantation practices may influence the development of cytomegalovirus (CMV) disease after renal transplantation.
From September 2003 through February 2005, 1470 renal transplant recipients (55 of whom were kidney-pancreas transplant recipients) were prospectively studied in the 16 transplant centers affiliated with the Spanish Network of Infection in Transplantation, with use of an ad hoc-designed online database. Univariate and multivariate analyses with logistic regression were performed to detect risk factors for CMV disease.
A total of 105 episodes of CMV disease (37 with visceral involvement) developed in 99 (6.7%) of 1470 patients. Attributable mortality appeared in 1 (1.0%) of 105 cases. Multivariate analysis showed that, apart from CMV serological mismatch, presence of rejection episodes, and the use of antilymphocitic drugs, a simultaneous pancreas transplantation (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-9), use of cyclosporine (OR, 1.7; 95% CI, 1.18-2.9), a donor >60 years of age (OR, 2.3; 95% CI, 1.5-3.7), and chronic graft malfunction (OR, 1.8; 95% CI, 1.14-2.9) were independently associated with CMV disease, whereas use of sirolimus had a protective effect (OR, 0.27; 95% CI, 0.1-0.78).
Additional risk factors related to current transplantation practices influence the epidemiology of CMV after renal transplantation and should be taken into account in the design of prophylactic strategies in this population of kidney or kidney-pancreas recipients.
Clinical Infectious Diseases 11/2008; 47(7):875-82. · 9.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Surgical site infections are common bacterial infections in orthotopic liver transplantation. The purpose of this study was to determine the incidence, timing, location, and risk factors, specifically antibiotic prophylaxis, for surgical site infections. A prospective study was performed that included a population of 1222 consecutive patients (73.0% males) who underwent liver transplantation in Spanish hospitals belonging to the Red de Estudio de la Infección en el Trasplante research network. One hundred seven patients developed surgical site infections. The predominant infection sites were incisional wound (53 episodes) and peritonitis (40 episodes). The timing of the organ/space surgical site infections was slightly delayed in comparison with incisional surgical site infections. Enterococcus spp., Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii were the predominant pathogens. Choledochojejunal or hepaticojejunal reconstruction (odds ratio, 4.2; 95% confidence interval, 1.6-10.7), previous liver or kidney transplant (odds ratio, 2.6; 95% confidence interval, 1.1-6.3), and more than 4 red blood cell units transfused (odds ratio, 2.0; 95% confidence interval, 1.1-3.4) were independently associated with the development of surgical site infections. Biliary reconstruction by choledochojejunostomy or hepaticojejunostomy increases the risk of surgical site infections.
Liver Transplantation 07/2008; 14(6):799-805. · 3.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recognizing a foreign element is an inherent characteristic of living beings and guarantees their survival. Evading this defense mechanism is one of the most difficult requirements for transplant success, but it leads to a series of consequences, mainly related to infection. T lymphocytes are the cornerstone of the allogenic response. These cells recognize intracellular and extracellular antigens over HLA molecules in host cells. As a consequence, lymphocytic expansion occurring on several levels is produced, and a humoral or cellular response is the final result. The immunosuppression regimens used in transplantation include induction, maintenance and rescue therapy. Induction therapy serves primarily to decrease the proportion of T-cell precursors and to lower the efficacy of antigen presentation. With respect to maintenance therapy, cyclosporine and tacrolimus inhibit cytokine transcription, azathioprine, and mycophenolate mofetil inhibit nucleotide synthesis, and sirolimus and everolimus inhibit transduction of growth factor signals. As a consequence of immunosuppression, opportunistic microorganisms may appear with endogenic reactivation of latent infection or from an exogenous origin. Prevention of these infections by proper knowledge of the risk factors, rapid diagnosis, and adequate management are fundamental to guarantee the survival of the patient.
Enfermedades Infecciosas y Microbiología Clínica 03/2007; 25(2):143-54. · 1.49 Impact Factor
-
Jose M. Aguado,
Jose A. Herrero,
Joan Gavaldá,
Julian Torre-Cisneros, Marino Blanes,
Gabriel Rufí,
Asunción Moreno,
Mercé Gurguí,
Marcelino Hayek,
Carlos Lumbreras,
the Spanish Transplantation Infection Study Group
[show abstract]
[hide abstract]
ABSTRACT: Background. Tuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients.
Methods. We evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation.
Results. The overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate.
Conclusions. M tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.
Transplantation 05/1997; 63(9):1278-1286. · 4.00 Impact Factor
-
Enfermedades infecciosas y microbiología clínica, ISSN 0213-005X, Vol. 25, Nº. 2, 2007, pags. 143-154.
