Extra-anatomic aortic bypass for the treatment of a mycotic pseudoaneurysm after liver transplantation for hilar cholangiocarcinoma

Liver transplantation (LT) after neoadjuvant chemoradiotherapy in patients with unresectable hilar cholangiocarcinoma (HC) is an accepted treatment strategy [1]. Neoadjuvant therapy is associated with an increased risk of arterial and portal complications after LT [1,2]. In most cases, radiation therapy makes the use of the native hepatic artery inadvisable, and an aortic anastomosis is needed, either with or without a graft [2]. The development of a mycotic pseudoaneurysm after LT is a rare complication that is associated with a high incidence of graft failure and mortality. Radiotherapy, local infections and the use of grafts are known risk factors for the development of a mycotic pseudoaneurysm, which is always challenging to manage [3]

The etiology, incidence, and impact of preservation fluid contamination during liver transplantation

The role of contaminated preservation fluid in the development of infection after liver transplantation has not been fully elucidated. To assess the incidence and etiology of contaminated preservation fluid and determine its impact on the subsequent development of infection after liver transplantation, we prospectively studied 50 consecutive liver transplants, and cultured the following samples in each instance: preservation fluid (immediately before and at the end of the back-table procedure, and just before implantation), blood, and bile from the donor, and ascitic fluid from the recipient. When any culture was positive, blood cultures were obtained and targeted antimicrobial therapy was started. We found that the incidence of contaminated preservation fluid was 92% (46 of 50 cases of liver transplantation per year), but only 28% (14/50) were contaminated by recognized pathogens. Blood and bile cultures from the donor were positive in 28% and 6% respectively, whereas ascitic fluid was positive in 22%. The most frequently isolated microorganisms were coagulase-negative staphylococci. In nine cases, the microorganisms isolated from the preservation fluid concurred with those grown from the donor blood cultures, and in one case, the isolate matched with the one obtained from bile culture. No liver transplant recipient developed an infection due to the transmission of an organism isolated from the preservation fluid. Our findings indicate that contamination of the preservation fluid is frequent in liver transplantation, and it is mainly caused by saprophytic skin flora. Transmission of infection is low, particularly among those recipients given targeted antimicrobial treatment for organisms isolated in the preservation fluid

Risk Factors and Outcomes of Acute Graft Pyelonephritis with Bacteremia Due to Multidrug-Resistant Gram-Negative Bacilli among Kidney Transplant Recipients

Acute graft pyelonephritis (AGP) is the leading cause of bloodstream infection in kidney transplant (KT) recipients. The prevalence of urinary tract infections caused by multidrug-resistant (MDR) Gram-negative bacilli is increasing. This 14-year prospective observational study sought to determine the clinical characteristics, risk factors, and outcomes of AGP with bacteremia due to MDR Gram-negative bacilli. Overall, 278 episodes of AGP with bacteremia due to MDR Gram-negative and non-MDR Gram-negative bacilli were identified and compared in 214 KT recipients; MDR Gram-negative bacilli were the cause in 28.4%. Overall 30-day mortality was low (1.1%). Risk factors independently associated with AGP due to MDR Gram-negative bacilli were male sex (OR 3.08; 95%CI 1.60-5.93), previous episode of bacteremic AGP (OR 2.11, 95%CI 1.09-4.09), prior antibiotic therapy in the preceding month (OR 2.47, 95%CI 1.33-4.57), and nosocomial acquisition (OR 2.03, 95%CI 1.14-3.62). Forty-three percent of MDR Gram-negative episodes received inappropriate empirical antibiotic therapy. The risk factors identified in this study may help physicians when selecting empirical antibiotic treatment for AGP. Previous antibiotic use was the main modifiable factor. Its presence highlights the importance of avoiding unnecessary antibiotics in order to bring down the high rates of MDR Gram-negative bacilli infections in this population

Neurological toxicity due to antimonial treatment for refractory visceral leishmaniasis

Introduction: Although pentavalent antimonials are no longer considered the first-line therapy for visceral leishmaniasis in the developed world, they are still used in certain geographical areas and in refractory cases. These drugs have a great number of adverse effects; however, neurological toxicity has been rarely reported. Case report: We present a 56-year-old woman who required long-term treatment with antimonial drugs due to refractory visceral leishmaniasis and presented clinically with tremor of extremities, myoclonus, gait disturbances and epileptic seizures. The EEG showed increased beta rhythms and generalized epileptogenic activity. She had a slow but favorable response after the withdrawal of antimonials and the initiation of anticonvulsant therapy. Conclusion: Severe but reversible neurological toxicity is a rare adverse effect of prolonged antimonial treatment. More EEG record data are needed to support the suspicion of a possible increase of beta rhythms in this situation. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V

Antibiotic treatment versus no treatment for asymptomatic bacteriuria in kidney transplant recipients: a multicenter randomized trial

Background: whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. Methods: in this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. Results: we enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40-4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50-8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P = .030), amoxicillin-clavulanic (P < .001) resistance, and extended-spectrum β-lactamase production (P = .044) were more common in KT recipients receiving antibiotic treatment for AB. Conclusions: antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed

Efficacy and safety of a booster dose of influenza vaccination in solid organ transplant recipients, TRANSGRIPE 1-2: study protocol for a multicenter, randomized, controlled clinical trial

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01761435 (registered 13 December 2012). EudraCT Identifier: 2011-003243-21 (registered 4 July 2011)

Risk factors, clinical features, and outcomes of listeriosis in solid-organ transplant recipients: a matched case-control study

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

doi.org/10.1371/journal. pone.0250796

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant periodThis study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016); co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014-2020. EC and JSC received grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARSCoV-2 y la enfermedad COVID-19 (COV20/ 00370; COV20/00580). JSC is a researcher belonging to the program “Nicola´s Monardes”(C0059–2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain. SS-A is supported by a grant from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-Co

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

Introduction: Healthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes. Methods: ITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality. Results: Four hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure. Conclusion: The rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure. © 2021, The Author(s)