Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with ...fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 91.6%) were produced by gram‐negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended‐spectrum β‐lactamase‐producing Enterobacteriaceae 14% or carbapenem‐resistant GNB 3.5%). A median daily dose of 1.5 g of fosfomycin (interquartile range IQR: 1.5‐2) was administered for a median of 7 days (IQR: 3‐10). Clinical cure (remission of UTI‐attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow‐up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98‐112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.
Fosfomycin can be considered a first choice alternative for the treatment of cystitis in kidney transplant recipients, particularly in view of recent safety concerns with fluoroquinolones.
Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early ...after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range IQR: 1.1 - 10.5). Most episodes (96.4% 132/137) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum β-lactamase-producing
20.4% and carbapenem-resistant GNB 2.9%). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval 95%CI: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio OR: 2.42; 95%CI: 1.11 - 5.29;
-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35;
-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.
Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies.
...Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax®).
Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly.
We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration.
There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment.
Invasive aspergillosis (IA) is associated with a high mortality rate in kidney-transplant recipients. Azole-resistance is increasing in Aspergillus fumigatus. We report a clinical case of a ...kidney-transplant recipient with cerebellar and pulmonary aspergillosis caused by azole-resistant Aspergillus parafelis (molecular identification through β-tubulin sequence). The patient experienced an effective resolution after three surgical procedures and associated antifungal therapy. This case highlights that azole-resistant aspergillosis should be considered in every patient with IA as long as susceptibility testing results are not known. Therefore, in selected patients with IA and central nervous system involvement, empirical combination antifungal therapy could be considered.
Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased ...risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG).
To study the incidence of CMV disease and its determinants.
Patients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence.
Forty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012).
The incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it.
Background. The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and ...1-y mortality of these patients. Methods. Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. Results. In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40–62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval 1.1-9.77; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 4–42 versus 11 3–21 d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 95% CI, 0.41-4.43, P = 0.618) did not differ between survivors and those who died. Conclusions. NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.
Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors.
Retrospective, multinational, 1:2 ...matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections.
Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years interquartile range {IQR} 40-62). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio aOR 1.04; 95 confidence interval CI, 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection.
Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.
Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased ...risk of infectious processes, such as cytomegalovirus disease (CMV); therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG).
To study the incidence of CMV disease and its determinants.
Patients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last ten years, who were determined the viral load of CMV, analyzing the determinants of its occurrence.
44 biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30,8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3,0, 95% CI: 1,0–8,9, p=0,012), and plasma albumin (for each g/L OR: 0,8, 95% CI: 0,6 to 1,0, p=0,012).
The incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it.
La afectación renal por glomerulonefritis necrosante pauci-inmune (GNPI) asociada a vasculitis de pequeño vaso requiere tratamiento inmunodepresor, cuyos efectos secundarios incluyen un mayor riesgo de procesos infecciosos, como la enfermedad por citomegalovirus (CMV), aunque no hay recomendaciones sobre su manejo en las guías de práctica clínica (GPC).
Estudiar la incidencia de enfermedad por CMV y sus determinantes.
Pacientes con diagnóstico histológico de GNPI en los últimos diez años, determinando la carga viral de CMV y analizando los determinantes de su concurrencia.
Se realizaron 44 biopsias durante el periodo de estudio. Del total, 11 pacientes (25%), desarrollaron enfermedad por CMV; todos habían recibido tratamiento inmunodepresor. Cuatro (30,8%), fallecieron durante el ingreso. Los factores determinantes de la enfermedad fueron la edad (por cada 10 años OR: 3,0, IC 95%: 1,0 a 8,9, p=0,012) y la albúmina (por cada g/L OR: 0,8, IC 95%: 0,6 a 1,0, p=0,012).
La incidencia de enfermedad por CMV en pacientes inmunodeprimidos por GNPI es alta, con alta mortalidad. Sería necesario incluir estrategias en las GPC para prevenir su desarrollo.
We describe the epidemiological pattern and genetic characteristics of 242 acute dengue infections imported to Europe by returning travellers from 2012 to 2014. The overall geographical pattern of ...imported dengue (South-east Asia > Americas > western Pacific region > Africa) remained stable compared with 1999 to 2010. We isolated the majority of dengue virus genotypes and epidemic lineages causing outbreaks and epidemics in Asia, America and Africa during the study period. Travellers acted as sentinels for four unusual dengue outbreaks (Madeira, 2012-13; Luanda, 2013; Dar es Salaam, 2014; Tokyo, 2014). We were able to characterise dengue viruses imported from regions where currently no virological surveillance data are available. Up to 36% of travellers infected with dengue while travelling returned during the acute phase of the infection (up to 7 days after symptom onset) or became symptomatic after returning to Europe, and 58% of the patients with acute dengue infection were viraemic when seeking medical care. Epidemiological and virological data from dengue-infected international travellers can add an important layer to global surveillance efforts. A considerable number of dengue-infected travellers are viraemic after arrival back home, which poses a risk for dengue introduction and autochthonous transmission in European regions where suitable mosquito vectors are prevalent.
PDF
