Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)

REIPI/INCREMENT-SOT Group.[Background] Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.[Methods] We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively.[Results] Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes.[Conclusions] Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).This work was supported by: (1) Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [RD16/0016/0001, RD16/0016/0002, REIPI RD16/0016/0008; RD16/0016/00010], co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligent Growth 2014-2020; (2) European Society of Clinical Microbiology and Infectious diseases Study Group for Infections in Compromised Hosts (ESGICH, grant to J.M.A.); (3) Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT, grant to L.M.M.); (4) Research project PI16/01631 integrated into the Plan Estatal de I+D+I 2013-2016 and co-financed by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación and the Fondo Europeo de Desarrollo Regional (FEDER); (5) M.F.R. holds a research contract “Miguel Servet” (CP 18/00073) from ISCIII, Ministerio de Ciencia, Innovación y Universidades. The work was also supported by the following European Society of Clinical Microbiology and Infectious diseases (ESCMID) study groups: Infections in Compromised Hosts (ESGICH), Bloodstream Infections and Sepsis (ESGBIS) and Antimicrobial Resistance Surveillance (ESGARS).Peer reviewe

Efecto de la Pentoxifilina en hepatitis colestásica aguda: reporte de dos casos

Introduction. Cholestatic hepatitis is a rare entity characterized by a bile flow obstruction,and it has a multi-factorial etiology. It can be acute or chronic and occasionally triggers fibrosis, cirrhosis and severe hepatitis. The current pharmacological management is based on corticosteroids and azathioprine or other drugs, such as, methotrexate, cyclosporine, budesonide, ursodeoxycholic acid, mefenamic acid, and pentoxifylline (PTX). We report two patients with autoimmune cholestatic hepatitis treated with pentoxifylline. Clinical cases. Two cases with diagnosis of cholestatic hepatitis confirmed by ultrasound and serological and histological studies. In both cases, corticosteroids were used as a pharmacological treatment without a favorable response. The therapy was replaced by pentoxifylline plus symptomatic treatment at base of ursodeoxycholic acid, vitamin E and cholestyramine. Both patients showed a remarkable improvement after two weeks of treatment. One of the patients showed a total bilirubin of 22.30 mg/dL with a decreased of direct bilirubin from 22.23 mg/dL to 2.10 mg/ dL; meanwhile, the second patient showed a total bilirubin of 63.7 mg/dL with a decreased of direct bilirubin levels from 60.2 mg/dL to 2.33 mg/ dL. In both patients the levels of transaminases decreased and an improvement of their clinical conditions were observed. Discussion. Our results showed that there was a favorable response in two patients treated with pentoxifylline. This drug has anti-inflammatory, anti-oxidant and anti-fibrotic effects as well as inhibitors effects of the transcription factor NF- κβ, so that it could be considered as an alternative treatment in patients with cholestatic hepatitis after validating its actual effectiveness.Introducción. La hepatitis colestásica es una entidad poco frecuente que se caracteriza por obstrucción del flujo biliar y presentar etiología multifactorial; puede ser aguda o crónica y, ocasionalmente, desencadena fibrosis, cirrosis y hepatitis grave. El manejo farmacológico habitual es a base de corticoides y azatioprina, así como otros medicamentos como el metotrexate, la ciclosporina, la budesonida, el ácido ursodesoxicólico, el ácido micofenólico y la pentoxifilina (PTX); dentro de los medicamentos citados, utilizamos pentoxifilina en dos pacientes con hepatitis colestásica autoinmune. Casos clínicos. Se reportan dos casos con diagnóstico de hepatitis colestásica, corroborada a través de estudios ecosonográfico, serológicos e histológicos. Se utilizaron corticoides para el tratamiento farmacológico en ambos casos; sin embargo, al no obtener resultados favorables, la terapia fue sustituida por pentoxifilina, más tratamiento sintomático a base de ácido ursodesoxicólico, vitamina E y colestiramina. Ambos pacientes mostraron una mejoría después de dos semanas de tratamiento; una paciente con bilirrubina total (BT) de 22.30 mg/dL disminuyó bilirrubina directa (BD) de 22.23 mg/dL a 2.10 mg/dL; en el segundo caso con BT de 63.7 mg/ dL disminuyó sus cifras de BD de 60.2 mg/dL a 2.33 mg/dL; además, redujo transaminasemia y las condiciones de ambas pacientes presentaron mejoría. Discusión. Nuestros resultados mostraron que hubo respuesta favorable en los dos pacientes tratados con pentoxifilina; considerando que este fármaco ha demostrado efectos antiinflamatorios, antioxidantes, antifibróticos e inhibidores del factor de transcripción NF-κβ, podría ser utilizado como un tratamiento alternativo en los pacientes con hepatitis colestásica, aclarando que se necesitan más estudios clínicos para validar su real eficacia

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective