Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG). METHODS: We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis. FINDINGS: Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference -29·6, 95% CI -50·5 to -8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up. INTERPRETATION: The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis. FUNDING: European Research Council and Fondo de Investigaciones Sanitarias.

New paradigms on antibiotic recommendations for community-acquired infections in Spain / Nuevos paradigmas en las recomendaciones antibióticas en las infecciones comunitarias en España

Over the last years, the susceptibility activity of the most common microorganisms causing community-acquired infections has significantly changed in Spain. Based on the susceptibility rates of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, and Klebsiella pneumoniae collected from outpatients aged 15 or older with symptoms of respiratory or urinary tract infections in several Microbiology Departments in Catalonia in 2021, penicillin V should be first choice for most respiratory tract infections, amoxicillin and clavulanate for chronic obstructive pulmonary disease exacerbations and a single dose of fosfomycin or a short-course nitrofurantoin should remain first-line treatments for uncomplicated urinary tract infections. Updated information on antimicrobial resistance for general practitioners is crucial for achieving appropriate empirical management of the most common infections by promoting more rational antibiotic use.(AU)

En los últimos años han cambiado significativamente los porcentajes de sensibilidad de los microorganismos más comunes que causan infecciones adquiridas en la comunidad en España. A partir de los porcentajes de sensibilidad de Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli y Klebsiella pneumoniae, recogidas de aislados de pacientes ambulatorios de 15 años o más, con síntomas de infecciones respiratorias o urinarias en servicios de microbiología de Cataluña en 2021, fenoximetilpenicilina debería ser la primera opción en la mayoría de los infecciones respiratorias, amoxicilina y ácido clavulánico en las exacerbaciones de la enfermedad pulmonar obstructiva crónica y la monodosis de fosfomicina o la pauta corta de nitrofurantoína como tratamiento de primera línea en las infecciones urinarias no complicadas. Es importante que los médicos de familia dispongan de información actualizada sobre la resistencia a los antimicrobianos para lograr un manejo empírico adecuado de las infecciones más frecuentes al promover un uso más racional de los antibióticos.(AU)

Improved management of cystitis in primary care following the implementation of a simple multifaceted intervention / Mejora en el manejo de las cistitis en atención primaria después de la implementación de una intervención multimodal simple

Objective: We assessed the impact of the implementation of a simple multifaceted intervention aimed at improving management of cystitis in primary care. Design: Quality control before and after study. Site: Primary care centres in Barcelona city provided by the Catalonian Institute of Health. Participants: The multifaceted intervention consisted of (1) creation of a group with a leader in each of the primary care centres, out of hours services, sexual and reproductive centres, and home visit service, (2) session on management of cystitis in each centre, (3) result feedback for professionals, and (4) provision of infographics for professionals and patients with urinary tract infections. Interventions started in November 2020 and ended in the summer of 2021. Main measurements: Variation in the prescription of first-line antibiotics, usage of antibiotics, and request for urine cultures before and after this intervention. Results: Training sessions took place in 93% of the centres. The use of first-line therapies cystitis increased by 6.4% after the intervention (95% confidence interval [CI], 5.7–7.1%). The use of nitrofurantoin in recurrent cystitis increased, mainly in out of hours service (8.7%; 95% CI, 5.2–12.2%). Urine cultures were more frequently requested after the intervention for recurrent cystitis in both primary care centres and out of hours services, with a 7.2% increase [95% CI, 5.9–8.5%), but also for uncomplicated urinary tract infections (3.1%; 95% CI, 1.8–4.4%). Conclusions: A low-intensity multifaceted intervention on management of cystitis, with strong institutional support, resulted in a better choice of antibiotic in antibiotic prescribing, but the intervention had less impact on the adequacy of urine cultures.(AU)

Objetivo: Evaluamos el impacto de una intervención multimodal en la mejora del manejo de las cistitis en atención primaria. Diseño: Estudio de calidad antes-después. Emplazamiento: Centros de atención primaria de la ciudad de Barcelona proporcionados por el Institut Català de la Salut. Participantes: La intervención multimodal consistió en: (1) creación de un grupo de trabajo con líderes en cada uno de los equipos de atención primaria, servicios de urgencias, centros de atención sexual y reproductiva y servicio de atención domiciliaria, (2) sesión formativa sobre el manejo de las infecciones del tracto urinario en cada centro, (3) retorno de resultados a profesionales, y (4) difusión de infografías a profesionales y pacientes. Las intervenciones comenzaron en noviembre de 2020 y finalizaron en verano de 2021. Mediciones principales: Variación en la prescripción de antibióticos de primera línea, uso de antibióticos y solicitud de urocultivos antes y después de esta intervención. Resultados: Las sesiones de formación se realizaron en el 93% de los centros. La selección de fármacos de primera línea en cistitis aumentó en un 6,4% después de la intervención (intervalo de confianza [IC] 95%: 5,7-7,1%). El uso de nitrofurantoína en cistitis recurrente aumentó, principalmente en servicios de urgencias (8,7%; IC 95%: 5,2-12,2%). Las solicitudes de urocultivos aumentaron después de la intervención en equipos de atención primaria y servicios de urgencias en cistitis recurrentes (7,2%; IC 95%: 5,9-8,5%), pero también en cistitis simples (3,1%; IC 95%: 1,8-4,4%). Conclusiones: Una intervención multimodal de baja intensidad sobre el manejo de las cistitis junto con el apoyo institucional explícito mejoró claramente la selección de antibióticos, pero tuvo menos impacto en la adecuación de los urocultivos.(AU)