Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy.

BACKGROUND & AIMS: There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. METHODS: Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. RESULTS: Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. CONCLUSIONS: VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. LAY SUMMARY: The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).

Aneurisma micótico por Salmonella enteritidis: descripción de un caso / Mycotic aneurysm caused by Salmonella enteritidis: a case report

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[Evaluation of methods for studying susceptibility to oxacillin and penicillin in 60 Staphylococcus lugdunensis isolates]. / Evaluación de métodos para el estudio de la sensibilidad a oxacilina y penicilina en 60 aislamientos de Staphylococcus lugdunensis.

INTRODUCTION: Staphylococcus lugdunensis is a coagulase-negative staphylococcus associated with a variety of clinical infections. In this paper we present the results of a comparative study using 4 methods to determine antimicrobial susceptibility to oxacillin and penicillin in 60 S. lugdunensis isolates. MATERIAL AND METHODS: We studied 60 S. lugdunensis isolates obtained from clinical specimens sent to our laboratory over an 8-year period. All isolates were free coagulase-negative and DNase-negative, and biochemically identified by API ID 32 STAPH (bioMérieux). Presence of mecA and ss-lactamase production were studied in all cases. Antimicrobial susceptibility was determined by the Vitek 2 System (bioMérieux) and broth microdilution (Wider) (Soria Melguizo) for penicillin and oxacillin, and the E-test (AB Biodisk) and cefoxitin disk diffusion test (BD BBLTM) for oxacillin. RESULTS: All isolates lacked the mecA gene and were susceptible to oxacillin by broth microdilution, E-test, and cefoxitin disk diffusion test. Only two isolates were oxacillin-resistant by the Vitek 2 System. Twenty-four isolates (40%) were ss-lactamase-positive, 4 after induction. Susceptibility testing to penicillin determined that 48 isolates showed concordance between the results obtained by broth microdilution and Vitek 2, but 12 isolates (20%), showed divergent results. CONCLUSIONS: We detected no resistance to oxacillin in S. lugdunensis. All the methods evaluated were adequate for determining oxacillin resistance. The Vitek 2 System is useful for detecting penicillin resistance, but the ss-lactamase test should be applied to isolates with a MIC=0.25microg/ml to avoid the interpretation of false resistance to this antibiotic.

Evaluación de métodos para el estudio de la sensibilidad a oxacilina y penicilina en 60 aislamientos de Staphylococcus lugdunensis / Evaluation of methods for studying susceptibility to oxacillin and penicillin in 60 Staphylococcus lugdunensis isolates

Introducción: Staphylococcus lugdunensis es un estafilococo coagulasa negativo relacionado con diversos tipos de infección. En este trabajo se presentan los resultados de un estudio comparativo mediante cuatro métodos para determinar la sensibilidad a oxacilina y penicilina. Material y métodos: se estudiaron 60 aislamientos de S. lugdunensis procedentes de muestras clínicas enviadas a nuestro laboratorio durante 8 años. Todos los aislados fueron coagulasa y DNasa negativos. La identificación se realizó bioquímicamente mediante API ID 32 STAPH (bioMérieux). En todos los casos se analizó la presencia de betalactamasa y la detección del gen mecA. La susceptibilidad antimicrobiana se determinó mediante: Vitek 2 System (bioMérieux) y microdilución en caldo (Wider) (Soria Melguizo) para oxacilina y penicilina; E-test (AB Biodisk) y método de difusión con disco de cefoxitina (BD BBLTM), para ensayar la sensibilidad a oxacilina. Resultados: todos los aislamientos fueron mecA negativos y sensibles a oxacilina en microdilución en caldo, E-test y en el método de difusión con cefoxitina, mientras que en Vitek 2 solamente dos aislamientos fueron resistentes a oxacilina; 24 (40%) fueron betalactamasa positivos, 4 tras inducción. Los resultados de susceptibilidad a penicilina mostraron que 48 aislamientos presentaban concordancia entre los obtenidos por microdilución en caldo y Vitek 2, pero 12 (20%) mostraron resultados discrepantes Conclusiones: en nuestro estudio no hemos hallado ningún aislamiento de S. lugdunensis resistente a oxacilina; los métodos de microdilución en caldo (Wider), E-test de oxacilina y difusión con disco de cefoxitina son adecuados para el estudio de sensibilidad a este antibiótico. El empleo del sistema Vitek 2 es útil para el estudio de la sensibilidad a penicilina si se aplica la prueba de betalactamasa a los aislamientos con concentración mínima inhibitoria (CMI) de 0,25μg/ml para evitar la interpretación de una falsa resistencia a dicho antibiótico (AU)

Introduction: Staphylococcus lugdunensis is a coagulase-negative staphylococcus associated with a variety of clinical infections. In this paper we present the results of a comparative study using 4 methods to determine antimicrobial susceptibility to oxacillin and penicillin in 60 S. lugdunensis isolates. Material and methods: We studied 60 S. lugdunensis isolates obtained from clinical specimens sent to our laboratory over an 8-year period. All isolates were free coagulase-negative and DNase-negative, and biochemically identified by API ID 32 STAPH (bioMérieux). Presence of mecA and ß-lactamase production were studied in all cases. Antimicrobial susceptibility was determined by the Vitek 2 System (bioMérieux) and broth microdilution (Wider) (Soria Melguizo) for penicillin and oxacillin, and the E-test (AB Biodisk) and cefoxitin disk diffusion test (BD BBLTM) for oxacillin. Results: All isolates lacked the mecA gene and were susceptible to oxacillin by broth microdilution, E-test, and cefoxitin disk diffusion test. Only two isolates were oxacillin-resistant by the Vitek 2 System. Twenty-four isolates (40%) were ß-lactamase-positive, 4 after induction. Susceptibility testing to penicillin determined that 48 isolates showed concordance between the results obtained by broth microdilution and Vitek 2, but 12 isolates (20%), showed divergent results. Conclusions: We detected no resistance to oxacillin in S. lugdunensis. All the methods evaluated were adequate for determining oxacillin resistance. The Vitek 2 System is useful for detecting penicillin resistance, but the ß-lactamase test should be applied to isolates with a MIC=0.25μg/ml to avoid the interpretation of false resistance to this antibiotic (AU)

[Microbiological diagnosis of upper respiratory tract infections]. / Diagnóstico microbiológico de las infecciones del tracto respiratorio superior.

Upper respiratory tract (URT) infections are common and account for more medical visits than any other type of infectious disease. Diagnostic procedures for the following syndromes are included in this report: Streptococcal and nonstreptococcal pharyngitis, laryngeal syndromes, otitis, sinusitis, and others caused by unusual and/or uncommon bacteria or fungi, including Lemierre's disease, Vincent's angina, pharyngeal and peritonsillar abscesses, diphtheria, candidiasis, and zygomycoses. Detailed information is provided on specimen collection and processing, selection of laboratory tests, interpretation of findings, reporting results, additional procedures for uncommon infections, and the use of new techniques. All the information included in this article is contained in the Standard Operating Procedures for Clinical Microbiology (http://www.seimc.org/protocolos/microbiologia/).

Diagnóstico microbiológico de las infecciones del tracto respiratorio superior / Microbiological diagnosis of upper respiratory tract infections

Las infecciones del tracto respiratorio superior se hallan entre las más frecuentes, y generan más consultas médicas que cualquier otro tipo de enfermedad infecciosa. Se incluyen los procedimientos de diagnóstico de los siguientes síndromes: faringitis estreptocócica y no estreptocócica, síndromes laríngeos, otitis, sinusitis y otras infecciones causadas por hongos y bacterias raros y/o poco frecuentes: síndrome de Lemierre, angina de Vincent, abscesos faríngeos y periamigdalares, difteria, candidiasis y zigomicosis. Se incluye información detallada sobre la recogida y procesamiento de las muestras, elección de pruebas de laboratorio, criterios de interpretación, información de (..) (AU)

Upper respiratory tract (URT) infections are common and account for more medical visits than any other type of infectious disease. Diagnostic procedures for the following syndromes are included in this report: Streptococcal and nonstreptococcal pharyngitis, laryngeal syndromes, otitis, sinusitis, and others caused by unusual and/or uncommon bacteria or fungi, including Lemierre's disease, Vincent's angina, pharyngeal and peritonsillar abscesses, diphtheria, candidiasis, and zygomycoses. Detailed information is provided on specimen collection and processing, selection of laboratory (AU)