Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: 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; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review / Infección del sistema nervioso central por Streptococcus bovis en adultos: reporte de 4 casos y revisión de la literatura

Objectives: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. Methods: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. Results: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). Conclusions: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.(AU)

Introducción: Streptococcus bovis, una causa bien conocida de endocarditis asociada a cáncer colorrectal, es también una causa poco frecuente de infecciones del sistema nervioso central (SNC), incluyendo meningitis, abscesos cerebrales o empiema subdural. El objetivo de este estudio es describir las características clínicas, los antecedentes médicos y la asociación con la enfermedad intestinal en las infecciones por S. bovis en el SNC. Métodos: Describimos 4 infecciones por S. bovis en el SNC en nuestra Unidad y, a continuación, presentamos una revisión bibliográfica de los artículos publicados entre 1975-2021 en PubMed/MEDLINE. Resultados: Se encontraron 52 estudios con 65 casos; 5 se excluyeron por datos incompletos. En total se analizaron 64 casos incluyendo nuestros 4: 55 con meningitis y 9 con infecciones focales intracraneales. Ambas infecciones se asociaron con frecuencia a condiciones subyacentes (70,3%) como la inmunosupresión (32,8%) o el cáncer (10,9%). En 23 casos se identificó un biotipo, siendo el más frecuente el biotipo ii (69,6%), y dentro de ellos, S. pasteurianus. En el 60,9% de los casos se detectaron enfermedades intestinales, siendo las más frecuentes las neoplasias (41,0%) y la infestación por Strongyloides (30,8%). La mortalidad global fue del 17,1%, con una tasa mayor en la infección focal (44,4 frente a 12,7%; p=0,001). Conclusiones: Las infecciones del SNC debidas a S. bovis son poco frecuentes y la forma clínica más común es la meningitis. En comparación con las infecciones focales, la meningitis tiene un curso más agudo, está menos asociada a la endocarditis y tiene una menor mortalidad. La inmunosupresión y la enfermedad intestinal fueron frecuentes en ambas infecciones.(AU)

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review.

OBJECTIVES: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.

Microascus gracilis y otomicosis

Microascus spp, teleomorfo de Scopulariopsis, es un hongo saprofito encontrado normalmente en suelo, alimentos, vegetales e incluso en ambientes interiores. Considerado un contaminante ambiental, se caracteriza por la resistencia intrínseca a los antifúngicos disponibles. Existen escasas referencias de infecciones por Microascus gracilis, asociándose como causa de eumicetoma o enfermedad diseminada en pacientes sometidos a trasplante pulmonar. Presentamos un caso de otomicosis por M. gracilis con el fin de considerar la búsqueda de hongos en los cultivos óticos y poner de relevancia el poder patógeno y colonizador de este agente.

Microascus spp, a teleomorph of Scopulariopsis, is a saprophytic fungus normally found in soil, food, vegetables, and even indoors. Considered an environmental pollutant, it is characterized by its intrinsic resistance to available antifungals. There are few references to infections by Microascus gracilis, associating it as a cause of eumycetoma or disseminated disease in lung transplant recipients. We present a case of otomycosis caused by M. gracilis, to consider the search for fungi in ear cultures and highlight the pathogenic and colonizing power of this agent.

Microscopía vs. biología molecular en el diagnóstico de infecciones protozoarias intestinales, ¿es el momento del cambio? / Microscopy vs. molecular biology in the diagnosis of intestinal protozoal infections, is it time for a change?

Introducción: El examen microscópico de las parasitosis intestinales, a partir de las heces concentradas del paciente, presenta una menor sensibilidad si se compara con las técnicas de diagnóstico molecular. Por ello, el objetivo del presente estudio ha sido comparar ambas técnicas, así como evaluar si existe correlación entre el examen microscópico y los ciclos umbrales (Ct) obtenidos para Blastocystis hominis. Material y métodos: Estudio retrospectivo de las muestras recibidas en el laboratorio de Microbiología durante septiembre de 2021. Se realizó la prueba de concentración MiniParasep SF® para la visualización microscópica y posteriormente se realizó la PCR con el panel Seegene AllplexTM Parasite Assay. Resultados: Un 27% (n=74) de las muestras fueron positivas por diagnóstico molecular, con un total de 87 parásitosdetectados. El 53% (n=39) fueron mujeres con una edad media de 47 ± 24 años. En el 76% (n=56) de los casos el servicio de procedencia fue Atención Primaria. El parásito hallado con más frecuencia fue B. hominis, 85% (n=64), seguido de Dientamoeba fragilis 20% (n=15) y Giardia lamblia 11% (n=8). En 13 casos se detectaron co-infección por dos parásitos (en 6 casos B. hominis + D. fragilis, y en 7 casos B. hominis + G. lamblia). En el diagnóstico microscópico se obtuvo un 9,5% (n=26) de positividad. El parásito hallado con más frecuencia fue B. hominis,84% (n=23), seguido de G. lamblia se visualizó en tres casos por microscopía. D. fragilis no se visualizó en ningún caso. En una muestra se observó coinfección de B. hominis + G. lamblia. Conclusiones: Las técnicas para el diagnóstico molecular de las parasitosis intestinales son rápidas, fiables y más sensibles que las técnicas microscópicas, mejorando el diagnóstico microbiológico y la calidad asistencial. (AU)

Introduction: Microscopic examination of the intestinal parasites, from the patient’s concentrated feces, has a lower sensitivity when compared to molecular diagnostic techniques. Therefore, the objective of this study has been to compare both techniques, as well as to evaluate whether there is a correlation between the microscopic examination and the threshold cycles (Ct) obtained for Blastocystis hominis. Material and methods: Retrospective study of the samples received in the Microbiology laboratory during September 2021. The MiniParasep SF® concentration test was performed for microscopic visualization and then PCR was performed with the Seegene AllplexTM Parasite Assay panel. Results: A 27% (n=74) of the samples were positive by molecular diagnosis, with a total of 87 parasites detected. 53% (n=39) were women with a mean age of 47 ± 24 years. In 76% (n=56) of the cases the service of origin was Primary Care. The most frequently found parasite was B. hominis, 85% (n=64), followed by Dientamoeba fragilis 20% (n=15) and Giardia lamblia 11% (n=8). Co-infection by two parasites was detected in 13 cases (B. hominis + D. fragilis in 6 cases, and B. hominis + G. lamblia in 7 cases). In the microscopic diagnosis, 9.5% (n=26) positivity was obtained. The most frequently found parasite was B. hominis, 84% (n=23), followed by G. lamblia, which was seen in three cases by microscopy. D. fragilis was not seen in any case. Coinfection of B. hominis + G. lamblia was observed in one sample. Conclusions: Techniques for molecular diagnosis of intestinal parasites are fast, reliable and more sensitive than microscopic techniques, improving microbiological diagnosis and quality of care. (AU)