Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.

Sex differences in hospitalized adult patients with cellulitis: A prospective, multicenter study.

OBJECTIVES: Sex differences in adult cellulitis, a frequent cause of hospitalization, have not been analyzed. These differences were investigated in a large cellulitis series. METHODS: This was a prospective observational study of 606 Spanish hospitalized cellulitis patients. Different comorbidities, clinical, diagnostic, and treatment data were compared between the sexes. Multiple logistic regression modeling was performed to determine the variables independently associated with sex. RESULTS: Overall 606 adult cellulitis patients were enrolled; 314 (51.8%) were male and 292 (48.2%) were female. Females were older (mean age 68.8 vs 58.9 years, p < 0.0001), less likely to have prior wounds (p = 0.02), and more likely to have venous insufficiency (p = 0.0002) and edema/lymphedema (p = 0.0003) than males. The location of the infection differed between the sexes (p = 0.02). Males were more likely to have positive pus cultures (p = 0.0008), the causing agent identified (p = 0.04), and higher rates of Staphylococcus aureus infection (p = 0.04) and received longer antibiotic treatment (p = 0.03). Factors independently associated with female sex in the multivariate analysis were older age (p < 0.0001), prior cellulitis (p = 0.01), presence of edema/lymphedema as the predisposing factor (p = 0.004), negative versus positive pus culture (p = 0.0002), and location of cellulitis other than in the lower extremities (p = 0.035). CONCLUSIONS: Differences between male and female patients with cellulitis were age, recurrence, presence of edema/lymphedema, positivity of pus culture, and topography of the infection.

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients.

Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.

Selection criteria of solid organ donors in relation to infectious diseases: A Spanish consensus.

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.

Executive summary of the Consensus Statement of the Transplant Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the National Transplant Organization (ONT) on the Selection Criteria of Donors of Solid Organs in relation to Infectious Diseases.

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.

Cellulitis in adult patients: A large, multicenter, observational, prospective study of 606 episodes and analysis of the factors related to the response to treatment.

BACKGROUND: Cellulitis is a frequent cause of hospital admission of adult patients. Increasing prevalence of multiresistant microorganisms, comorbidities, predisposing factors and medical and surgical therapies might affect cellulitis response and recurrence rate. METHODS: Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, diagnostic, treatment (surgical and antibiotic) data were analyzed according to the cellulitis response. Good response implied cure. Poor response implied failure to cure or initial cure but relapse within 30 days of hospital discharge. RESULTS: Mean age was 63.3 years and 51.8% were men. Poor responses were significantly associated with age, previous episodes of cellulitis, prior wounds and skin lesions, venous insufficiency, lymphedema, immunosuppression and lower limbs involvement. No differences in ESR or CRP blood levels, leukocyte counts, pus or blood cultures positivity or microbiological or imaging aspects were observed in those with good or poor responses. Regarding antimicrobials, no differences in previous exposition before hospital admission, treatment with single or more than one antibiotic, antibiotic switch, days on antimicrobials or surgical treatment were observed regarding good or poor cellulitis response. Prior episodes of cellulitis (P = 0.0001), venous insufficiency (P = 0.004), immunosuppression (P = 0.03), and development of sepsis (P = 0.05) were associated with poor treatment responses, and non-surgical trauma (P = 0.015) with good responses, in the multivariate analysis. CONCLUSIONS: Prior episodes of cellulitis, non-surgical trauma, venous insufficiency, sepsis and immunosuppression were independently associated with treatment response to cellulitis, but not the causative microorganism, the number of antimicrobials administered or its duration.

Is Visceral Leishmaniasis Different in Immunocompromised Patients Without Human Immunodeficiency Virus? A Comparative, Multicenter Retrospective Cohort Analysis.

Although visceral leishmaniasis (VL) can affect immunocompromised patients, data from the human immunodeficiency virus (HIV) infection context are limited, and the characteristics of VL in other immunosuppression scenarios are not well defined. A retrospective review of all cases of VL in immunocompromised patients from January 1997 to December 2014 in two Spanish hospitals on the Mediterranean coast was performed. We included 18 transplant recipients (kidney: 7, liver: 4, lung: 3, heart: 2, and blood marrow: 2), 12 patients with other causes of immunosuppression (myasthenia gravis: 3 and rheumatoid arthritis: 2), and 73 VL HIV-positive patients. Fever was more common in transplant patients (94.4%) and patients with other types of immunosuppression (100%) than in HIV-positive individuals (73.3%). Hepatomegaly was less common in transplant recipients (27.8%) and patients with other types of immunosuppression (41.7%) compared with HIV-positive patients (69.9%) (P = 0.01; P = 0.001, respectively). Patients with other types of immunosuppression had a median leukocyte count of 1.5 × 109/L, significantly lower than HIV-positive patients (2.5 × 109/L) (P = 0.04). Serology was more commonly positive in nontransplant immunosuppressed individuals (75%) and transplant recipients (78.6%) than in HIV-patients (13.8%) (P < 0.001). Antimonial therapy was rarely used in transplant recipients (1.9%) and never in patients with other immunosuppressive conditions, whereas 34.2% of HIV-positive patients received it (P = 0.05 and P = 0.01, respectively). Mortality was 16.7% in both transplant recipients and patients with other immunosuppressive conditions and 15.1% in HIV-positive patients. The features of VL may be different in immunosuppressed patients, with more fever and less hepatomegaly and leukopenia than in HIV-infected patients.

Human immunodeficiency virus-infected liver transplant recipients with incidental hepatocellular carcinoma: A prospective multicenter nationwide cohort study.

There is a lack of data on incidental hepatocellular carcinoma (iHCC) in the setting of liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients. This study aims to describe the frequency, histopathological characteristics, and outcomes of HIV+ LT recipients with iHCC from a Spanish multicenter cohort in comparison with a matched cohort of LT patients without HIV infection. A total of 15 (6%) out of 271 patients with HIV infection who received LT in Spain from 2002 to 2012 and 38 (5%) out of the 811 HIV- counterparts presented iHCC in liver explants (P = 0.58). Patients with iHCC constitute the present study population. All patients also had hepatitis C virus (HCV)-related cirrhosis. There were no significant differences in histopathological features of iHCC between the 2 groups. Most patients showed a small number and size of tumoral nodules, and few patients had satellite nodules, microvascular invasion, or poorly differentiated tumors. After a median follow-up of 49 months, no patient developed hepatocellular carcinoma (HCC) recurrence after LT. HIV+ LT recipients tended to have lower survival than their HIV- counterparts at 1 (73% versus 92%), 3 (67% versus 84%), and 5 years (50% versus 80%; P = 0.06). There was also a trend to a higher frequency of HCV recurrence as a cause of death in the former (33% versus 10%; P = 0.097). In conclusion, among LT recipients for HCV-related cirrhosis, the incidence and histopathological features of iHCC in HIV+ and HIV- patients were similar. However, post-LT survival was lower in HIV+ patients probably because of a more aggressive HCV recurrence. Liver Transplantation 23 645-651 2017 AASLD.

Human immunodeficiency virus infection does not worsen prognosis of liver transplantation for hepatocellular carcinoma.

UNLABELLED: The impact of human immunodeficiency virus (HIV) infection on patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) is uncertain. This study aimed to assess the outcome of a prospective Spanish nationwide cohort of HIV-infected patients undergoing LT for HCC (2002-2014). These patients were matched (age, gender, year of LT, center, and hepatitis C virus (HCV) or hepatitis B virus infection) with non-HIV-infected controls (1:3 ratio). Patients with incidental HCC were excluded. Seventy-four HIV-infected patients and 222 non-HIV-infected patients were included. All patients had cirrhosis, mostly due to HCV infection (92%). HIV-infected patients were younger (47 versus 51 years) and had undetectable HCV RNA at LT (19% versus 9%) more frequently than non-HIV-infected patients. No significant differences were detected between HIV-infected and non-HIV-infected recipients in the radiological characteristics of HCC at enlisting or in the histopathological findings for HCC in the explanted liver. Survival at 1, 3, and 5 years for HIV-infected versus non-HIV-infected patients was 88% versus 90%, 78% versus 78%, and 67% versus 73% (P = 0.779), respectively. HCV infection (hazard ratio = 7.90, 95% confidence interval 1.07-56.82) and maximum nodule diameter >3 cm in the explanted liver (hazard ratio = 1.72, 95% confidence interval 1.02-2.89) were independently associated with mortality in the whole series. HCC recurred in 12 HIV-infected patients (16%) and 32 non-HIV-infected patients (14%), with a probability of 4% versus 5% at 1 year, 18% versus 12% at 3 years, and 20% versus 19% at 5 years (P = 0.904). Microscopic vascular invasion (hazard ratio = 3.40, 95% confidence interval 1.34-8.64) was the only factor independently associated with HCC recurrence. 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.

[Boosted protease inhibitor monotherapy in HIV-infected patients: results of a study in a real life setting]. / Monoterapia con inhibidores de la proteasa potenciados en pacientes infectados por el VIH: resultados de un estudio en la "vida real".

BACKGROUND: Boosted protease inhibitor monotherapy may offer antiviral efficacy while reducing drug interactions, costs and toxicity. The aim of this study was to assess the efficacy of darunavir/ritonavir (DRV/r) and lopinavir/ritonavir (LPV/r) monotherapy in a real life setting. METHODS: A retrospective analysis of all HIV infected patients, who had initiated DRV/r or LPV/r monotherapy, was performed. Patients whose HIV viral load had remained undetectable for at least two consecutive follow-up visits and who had no neurocognitive disorder or hepatitis B co-infection, were included. RESULTS: Sixty patients were included. The median (IQR) time to follow-up was 66 (33-118) weeks. The proportions (CI95%) of patients with virological failure were 6.3% (1.7- 20.2) and 25.0% (12.7-43.4), respectively, in the DRV/r and LPV/r groups (p= 0.0424). The proportions (CI95%) of patients with therapeutic success were 90.6% (80.5-100) in the DRV/r group and 60.7% (42.6-78.8) in the LPV/r group (p=0.0063). No protease inhibitor mutations were detected. During the follow-up, 6 patients with dyslipidemia normalized their lipid values. The median monthly cost was 410 (IQR 242-416) euros per person lower for the monotherapy than for the combined antiretroviral therapy. CONCLUSIONS: Boosted protease inhibitor monotherapy was effective in a real life setting. This study showed differences in favour of DRV/r as compared with LPV/r in terms of therapeutic success; however prospective studies are needed to confirm these results. Finally, although this study was not specifically designed to detect benefits in terms of costs and lipid profile, it shows evidence of a positive impact of monotherapy in these fields.

Tuberculosis prophylaxis with levofloxacin in liver transplant patients is associated with a high incidence of tenosynovitis: safety analysis of a multicenter randomized trial.

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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.

[Cerebral phaeohyphomycosis: description of a case and review of the literature]. / Feohifomicosis cerebral: descripción de un caso y revisión de la literatura.

Cerebral phaeohyphomycosis is a rare invasive fungal infection with very few cases referenced in the literature. There is no standardized treatment, and it is associated with poor outcomes. Cladophialophora bantiana, a fungus with special tropism for the central nervous system, is one of the causal agents of phaeohyphomycosis. The case presented here deals with a brain abscess by C. bantiana in an adult with Crohn's disease had beed being treated with immunosuppressive drugs. Despite the correct etiological diagnosis, surgical and pharmacological treatments, the patient died 32 days after surgery. A description of the case is followed by a review of all cerebral C. bantiana phaeohyphomycosis cases published in the last 10 years. Regardless of the use of advanced new imaging techniques in the diagnosis and treatment with new antifungal agents, cerebral phaeohyphomycosis by C. bantiana continues to have very poor prognosis. While new more successful therapeutic treatments appear, a combined surgical and pharmacological approach seems to be more appropriate for this severe mycosis.

Haemophagocytic syndrome in a liver transplant patient during treatment with Telaprevir.

Haemophagocytic syndrome (HS) is a rare disease that is often fatal despite treatment. HS is characterized by fevers, lymphadenopathy, hepatosplenomegaly, cytopenias and hyperferritinaemia due to deregulated activation and proliferation of macrophages, leading to uncontrolled phagocytosis of platelets, erythrocytes, lymphocytes, and their hematopoietic precursors throughout the reticuloendothelial system. Mycobacterium tuberculosis-associated HS is a rare and underdiagnosed association with only 39 cases reported. We describe a case of HS associated with disseminated Mycobacterium tuberculosis in the setting of post-liver transplantation anti-hepatitis C therapy with pegylated interferon (pegIFN), ribavirin (RBV) and telaprevir (TVR). Despite the delay in the etiologic diagnosis, the patient was treated properly with corticosteroids, cyclosporine and tuberculostatic agents. It is unknown whether telaprevir, a drug that only recently has been started off-label in liver transplant recipients, may have contributed to the development of the HS. Unfortunately, as in many reported cases of HS, the outcome was unfavourable resulting in the death of the patient.

Outcome of Clostridium difficile-associated disease in solid organ transplant recipients: a prospective and multicentre cohort study.

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.

Infections in solid organ transplantation in special situations: HIV-infection and immigration.

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.

Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort study.

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.

Universal prophylaxis with fluconazole for the prevention of early invasive fungal infection in low-risk liver transplant recipients.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Selective intestinal decontamination with fluoroquinolones for the prevention of early bacterial infections after liver transplantation.

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.

Kidney transplants in HIV-positive recipients under HAART. A comprehensive review and meta-analysis of 12 series.

BACKGROUND: Kidney transplantation is being introduced gradually for the treatment of end-stage renal disease in patients who are human immunodeficiency virus (HIV) positive. Our aim was to review the outcomes of kidney transplantation in HIV-positive recipients who were being treated with highly active antiretroviral therapy (HAART). METHODS: Eligible papers were English language manuscripts, published between July 2003 and April 2009 and available through Medline, that described three or more recipients of kidney transplants who were HIV positive and undergoing HAART. The regimens for induction and maintenance therapy, organ rejection, patient survival, CD4 counts, HIV progression, infectious complications and deaths were recorded. The survival at 1 year, organ rejection and infectious complications were evaluated using a random effects model with 95% confidence intervals (CI). RESULTS: Twelve case series met the defined criteria. Induction therapy consisted most commonly of the administration of anti-CD25 monoclonal antibodies, and triple immunosuppressive therapy was used most commonly for maintenance. Among the 254 patients, 1-year survival was 0.93 (95% CI, 0.90-0.96), organ rejection was diagnosed in 0.36 (95% CI, 0.25-0.49) and infectious complications occurred in 0.29 (95% CI, 0.17-0.43). The CD4 counts decreased after transplantation but recovered later. Acquired immune deficiency syndrome (AIDS)-defining infections occurred in three patients. CONCLUSIONS: Kidney transplantation appears to be safe in patients undergoing HAART. However, larger series of patients are needed to determine the best protocols for the induction and maintenance of immunosuppression.