The effect of an antimicrobial stewardship programme in two intensive care units of a teaching hospital: an interrupted time series analysis.

OBJECTIVES: To evaluate the effect of an antimicrobial stewardship programme in two intensive care units (ICUs) of a teaching hospital. METHODS: Between January 2017 and June 2018 we conducted a prospective, interventional, interrupted time-series study, based on Prospective Audit and Feedback in two ICUs of an acute-care teaching hospital. The primary outcomes were the difference in the antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug-resistant (MDR) organisms. The secondary outcomes included the hospital mortality rate, the mean length of stay and the antibiotic expense. RESULTS: During the study, 231 audits were performed, evaluating 693 antibiotic prescriptions. The programme led to a global reduction in antibiotic consumption, with a change in level (CL) of -324.8 defined daily doses (DDD)/100 patient-days (PD), p 0.04, and particularly in the use of fluoroquinolone: (CL: -63.48 DDD/100 PD, p < 0.001). A non-significant reduction was obtained for the consumption of carbapenems (CL: -34.7 DDD/100 PD, p 0.25) and third- and fourth-generation cephalosporins (CL: -27.3 DDD/100 PD, p 0.102). Furthermore, we registered a significant decrease in all BSI (CL: -5.8 events/100 PD, p 0.026) and in BSI due to MDR Gram-negative organisms (CL: -2.96 events/100 PD, p 0.043). No difference was observed in the hospital mortality and length of stay. CONCLUSIONS: Our study demonstrated that implementation of an antimicrobial stewardship programme in two ICUs of a teaching hospital induced a significant reduction in antibiotic consumption and in the incidence of BSI due to MDR Gram-negative organisms, without any impact on the mortality rate.

Complex trauma, PTSD and complex PTSD in African refugees.

Background: The introduction of the diagnosis of complex posttraumatic stress disorder (CPTSD) by ICD-11 is a turning point in the field of traumatic stress studies. It's therefore important to examine the validity of CPTSD in refugee groups exposed to complex trauma (CT) defined as a repeated, prolonged, interpersonal traumatic event. Objective: The objective of this study was to compare DSM-5 and ICD-11 post-traumatic stress disorder diagnoses and to evaluate the discriminant validity of ICD-11 PTSD and CPTSD constructs in a sample of treatment-seeking refugees living in Italy. Method: The study sample included 120 treatment-seeking African refugees living in Italy. All participants were survivors of at least one CT. PTSD and CPTSD diagnoses were assessed according to both DSM-5 and ICD-11 criteria. Results: Findings revealed that 79% of the participants met the DSM-5 criteria for PTSD, 38% for ICD-11 PTSD and 30% for ICD-11 CPTSD. Generally, ICD-11 CPTSD items evidenced strong sensitivity and negative predictive power, low specificity and positive predictive power. Latent class analysis results identified two distinct groups: (1) a PTSD class, (2) a CPTSD class. None of the demographic and trauma-related variables analysed was significantly associated with diagnostic group. On the other hand, the months spent in Italy were significantly associated with PCL-5 score. Conclusions: Findings extend the current evidence base to support the discriminant validity of PTSD and CPTSD amongst refugees exposed to torture and other gross violations of human rights. The results suggest also that, in the post-traumatic phase, the time spent in a 'safe place' condition contributes to improve the severity of post-traumatic symptomatology, but neither this variable nor other socio-demographic factors seem to contribute to the emergence of complex PTSD. Further investigations are needed to clarify which specific vulnerability factors influence the development of PTSD or CPTSD in refugees exposed to complex trauma.

Antecedentes: La introducción del diagnóstico del trastorno de estrés postraumático complejo (TEPT-C) por la CIE-11 es un punto de inflexión en el campo de los estudios del estrés traumático. Por lo tanto, es importante examinar la validez del TEPT-C en los grupos de refugiados expuestos a un trauma complejo (TC) definido como un evento traumático interpersonal prolongado y repetido.Objetivo: El objetivo de este estudio fue comparar los diagnósticos de trastorno de estrés postraumático del DSM-5 y la CIE-11 y evaluar la validez discriminante de los constructos del TEPT y TEPT-C de la CIE-11 en una muestra de refugiados en busca de tratamiento que viven en Italia.Método: La muestra del estudio incluyó a 120 refugiados africanos que buscan tratamiento y que viven en Italia. Todos los participantes fueron sobrevivientes de al menos un TC. Los diagnósticos de TEPT y TEPT-C se evaluaron de acuerdo con los criterios del DSM-5 y de la CIE-11.Resultados: Los hallazgos muestran que el 79% de los participantes cumplieron con los criterios del DSM-5 para el TEPT, el 38% para el TEPT de la CIE-11 y el 30% para el TEPT-C de la CIE-11. En general, los ítems de TEPT-C de la CIE-11 evidenciaron una fuerte sensibilidad y poder predictivo negativo, baja especificidad y poder predictivo positivo. Los resultados del análisis de clase latente identificaron dos grupos distintos: (1) grupo de TEPT, (2) grupo de TEPT-C. Ninguna de las variables demográficas y relacionadas con el trauma analizadas se asoció significativamente con el grupo de diagnóstico. Por otro lado, los meses pasados en Italia se asociaron significativamente con la puntuación de PCL-5.Conclusiones: Los hallazgos amplían la base de evidencia actual para apoyar la validez discriminante del TEPT y el TEPT-C entre los refugiados expuestos a tortura y otras violaciones graves de los derechos humanos. Los resultados sugieren también que, en la fase postraumática, el tiempo pasado en una condición de "lugar seguro" contribuye a mejorar la gravedad de la sintomatología postraumática, pero ni esta variable ni otros factores sociodemográficos parecen contribuir a la aparición del TEPT-C. Se necesitan más investigaciones para aclarar qué factores de vulnerabilidad específicos influyen en el desarrollo de TEPT o TEPT-C en los refugiados expuestos a trauma complejo.

Flexible enzymatic activation of artificial polyketide extender units by Streptomyces cinnamonensis into the monensin biosynthetic pathway.

Streptomyces cinnamonensis A495 is a variant of the monensin producer which instead of the native polyether antibiotic gives rise to antibiotic and anti-tumour shunt-product premonensin. Through the supplementation of the fermentation medium with suitable precursors, premonensin can be derivatized via the incorporation of new-to-nature extender units into the biosynthetic machinery. Polyketide extender units require activation, typically in form of coenzyme A-thioesters. These are membrane impermeable and thus in the past an artificial mimic was employed. Here, we show the use and preliminary characterization of a highly substrate promiscuous new enzyme for the endogenous thioester formation in a Streptomyces strain. These intracellularly activated alternative extender units are significantly better incorporated into premonensin than the synthetically activated counterparts. SIGNIFICANCE AND IMPACT OF THE STUDY: Polyketide natural products are of enormous relevance in medicine. The hit-rate in finding active compounds for the potential treatment of various diseases among this substance family of microbial origin is high. However, most polyketides require derivatization to render them suitable for the application. Of relevance in this field is the incorporation of artificial substances into the biogenesis of polyketides, hampered by both the microbial metabolism and the complexity of the enzymes involved. This manuscript describes the straightforward and selective biosynthetic incorporation of synthetic substances into a reduced polyketide and showcases a promising new enzyme to aid this purpose.