Programa de optimización de antibioterapia en infección urinaria por cepas multirresistentes en el servicio de urgencias / Antimicrobial stewardship program in urinary tract infections due to multi resistant strains in the emergency department

Introducción. Las infecciones urinarias (ITU) son un mo tivo frecuente de asistencia a los servicios de urgencias hospi talarias (SU), siendo cada vez más frecuente el aislamiento de cepas multirresistentes. El presente trabajo pretende evaluar el impacto de un programa multidisciplinar de optimización de antibioterapia en pacientes con ITU causada por bacterias mul tirresistentes atendidas desde el SU. Material y métodos. Estudio descriptivo de la puesta en marcha de un programa en el que participaron los servicios de urgencias, microbiología y farmacia. El tratamiento antibiótico de los pacientes que consultaron urgencias con urinocultivos positivos para bacterias multirresistentes fue revisado al alta por el equipo multidisciplinar. En aquellos pacientes con tra tamiento inapropiado se contactó con los médicos y/o farma céuticos del siguiente nivel asistencial o con los propios pa cientes en el caso de alta a domicilio. Se evaluó el impacto del programa sobre las nuevas consultas a urgencias a 30 días en comparación con los resultados obtenidos de la práctica habi tual en tres meses previos a la intervención. Resultados. Durante el año de implantación se revisaron 2.474 urinocultivos de pacientes con ITU, 537 (21,7%) causa das por bacterias multirresistentes. El tratamiento empírico al alta de urgencias fue inapropiado en 287 (53,4%) pacientes, realizando modificaciones del tratamiento en 232 de ellos. 73 pacientes (19,3%) reconsultaron el SU a los 30 días del alta, siendo este porcentaje inferior a los resultados obtenidos en los tres meses previos a la intervención (27,9%; p=0,031), sin encontrar diferencias significativas en el porcentaje de nuevas visitas asociadas a infecciones urinarias. Conclusión (AU)

Introduction. Urinary tract infections (UTI) are a fre quent reason for attendance at emergency department (ED). The present study evaluates the impact of a multidisciplinary program for the optimization of antibiotic therapy in patients with UTI caused by multi-drug resistant bacteria treated from the hospital ED. Material and methods. Descriptive study of the imple mentation of a program in which emergency, microbiology and pharmacy departments participated. Antibiotic treatment of the patients who consulted the ED with positive urine cul tures caused by multidrug-resistant bacteria was reviewed up on discharge. In those patients with inappropriate treatment, doctors and/or pharmacists of the next level of healthcare or patients in the case of home discharge were contacted. The impact of the program was evaluated based on new visits to the ED at 30 days after discharge, compared with the results obtained from the usual practice three months prior the in tervention. Results. During the first year, 2,474 urine cultures of pa tients with UTI were reviewed, 533 (21.7%) were caused by multidrug-resistant bacteria. Empirical treatment was inap propriate in 287 (53.4%), making treatment modifications in 243 of them. 73 (19.3%) patients returned to the ED 30 days after discharge, being lower than the results obtained in the three months prior intervention (27.9%; p=0.031), without significant differences in new visits associated with UTI. Conclusion. The implementation of a multidisciplinary program focused on multidrug resistant UTI at discharge form ED correct antibiotic therapy in a large number of patients, be ing a potentially tool to reduce the number of new ED visits (AU)

PREDICTION OF MULTIDRUG-RESISTANT BACTERIA IN URINARY TRACT INFECTIONS IN THE EMERGENCY DEPARTMENT.

BACKGROUND: Urinary tract infections (UTI) due to multidrug-resistant bacteria are a frequent reason for visiting the emergency department (ED). OBJECTIVES: The aim of this study was to evaluate the applicability of a predictive model of infection by multidrug-resistant microorganisms in UTIs treated in an ED. METHODS: This is a retrospective observational study. Adult patients admitted to an ED with a diagnosis of UTI and positive urine culture were included. The main objective was to evaluate the area under the curve of the receiver operating characteristic (AUC-ROC), the scale proposed by González-del-Castillo, considering infection by a resistant pathogen as the dependent variable and the scale score of the predictive model used as the independent variable. RESULTS: The study included 414 patients with UTIs, 125 (30.2%) of which were caused by multidrug-resistant microorganisms. A total of 38.4% of patients were treated with antibiotics during the previous 3 months and a multidrug-resistant pathogen was isolated from 10.4% of the total during the previous 6 months. The AUC-ROC of the scale for predicting UTIs due to multidrug-resistant microorganisms was 0.79 (95% confidence interval 0.76-0.83), the optimal cut-off point being 9 points, with a sensitivity of 76.8% and a specificity of 71.6%. CONCLUSIONS: The use of the predictive model evaluated is a useful tool in real clinical practice to improve the success of empirical treatment of patients presenting to the ED with a diagnosis of UTI and positive urine culture pending identification.

Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab.

Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4wks or extended interval dose (EID) of 300 mg/6wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual's dosing schedule.

Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates.

BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10-76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification.

Leukocyte adhesion molecule dynamics after Natalizumab withdrawal in Multiple Sclerosis.

Cell-adhesion molecules (CAMs) dynamics in Multiple Sclerosis (MS) patients have been widely studied after Natalizumab (NTZ) introduction. However, their temporal dynamics after NTZ withdrawal (NTZ-W) has not been described. We prospectively evaluate changes in the expression levels of CAMs (CD49d, CD29, L-Selectin and CD11a) involved in T cell migration of 22 MS patients after NTZ-W. CD49d, CD29 and CD11a expression experienced a continuous increase expression two months after NTZ-W and Cd49d expression at month six after NTZ-W correlated to NTZ treatment duration, both in CD45+CD4+ and CD45+CD8+. CD49d expression up to month three after NTZ-W was related to MS activity in CD45+CD8+ at the end of the study. Results from this study suggest that patients with a longer NTZ treatment are more susceptible to present a "molecular rebound" after NTZ-W. CD49d determination may be a useful tool to closely monitor MS activity in patients who interrupt NTZ.

Absence of MxA induction is related to a poor clinical response to interferon beta treatment in multiple sclerosis patients.

The aim of this study is to investigate whether induction of myxovirus resistance protein A (MxA) mRNA after 3 months of interferon-ß administration is related to the treatment response in multiple sclerosis (MS) patients. In this prospective study, MS patients were enrolled before starting treatment. Demographic, clinical and radiological variables were recorded. Blood samples were obtained before, and at 3 and 12 months after interferon-ß treatment. Real-time PCR was used to analyze MxA mRNA expression. Patients were classified as MxA-low or -high depending on MxA levels at baseline, and as MxA-induced or -non-induced according to whether an increase in MxA expression was detected at month 3. Time to the next relapse was investigated using Cox proportional hazards regression analysis. One hundred and four patients were selected and followed for a median of 2.2 years (IQR 1.6-3.5). On Cox regression analysis, a higher EDSS score before treatment (HR 1.57; 95 % CI 1.02-2.40; p = 0.039), MxA-high status at baseline (HR 2.71; 95 % CI 1.26-5.81; p = 0.010), and MxA-non-induced at month 3 (HR 2.49; 95 % CI 1.08-5.68; p = 0.031), were predictors of poor response to interferon-ß in naïve MS patients. Patients showing a lower capacity for MxA induction following 3 months of interferon-ß treatment are more likely to be non-responders to this therapy.

Effect of the type of dietary fat on biliary lipid composition and bile lithogenicity in humans with cholesterol gallstone disease.

OBJECTIVE: The effect of the type of dietary fat on bile lipids and lithogenicity is unclear. This study compared the effects of two dietary oils that differed in fatty acid profile on biliary lipid composition in humans. METHODS: Female patients who had cholesterol gallstones and were scheduled for elective cholecystectomy were studied. For 30 d before surgery, subjects were kept on diets that contained olive oil (olive oil group, n = 9) or sunflower oil (sunflower oil group, n = 9) as the main source of fat. Gallbladder bile and stones were sampled at surgery. After cholecystectomy, duodenal samples were collected by nasoduodenal intubation during fasting and after administration of mixed liquid meals that included the corresponding dietary oil. Duodenal and gallbladder bile samples were analyzed for cholesterol, phospholipids, and total bile acids by established methods. Individual bile acid conjugates in gallbladder bile were measured by high-performance liquid chromatography. Gallstones were analyzed by semiquantitative polarizing light microscopy. RESULTS: Despite marked differences in the absolute concentration of biliary lipids and total lipid content, manipulation of dietary fat ingestion did not influence the cholesterol saturation or the profile of individual bile acids in gallbladder bile obtained from patients who had gallstones. All but one subject had mixed cholesterol stones. A cholesterol saturation index of hepatic bile in fasted cholecystectomized patients was similar in both dietary groups and indicative of supersaturation. In response to the test meal, the cholesterol saturation index decreased significantly in patients given the olive oil diet, reaching values lower than one at 120 min postprandially. In contrast, hepatic bile secreted by patients who consumed sunflower oil appeared supersaturated (cholesterol saturation index >1.5) throughout the experiment. CONCLUSIONS: Our results suggest that the type of dietary fat habitually consumed can influence bile composition in humans. In gallbladder, this influence was noted in the presence of more concentrated bile in the olive oil group. However, this was not translated into a modification of cholesterol saturation, which is likely due to the fact that cholesterol gallstones were present by the time the dietary intervention started. The finding that a typical postprandial variation in hepatic bile lithogenicity occurred only in olive oil patients was revealing. While keeping in mind the methodologic limitations of this part of the study, some gastrointestinal and metabolic mechanisms for this effect are discussed.

Medical assessment in drug addicts: reliability and validity of the Cumulative Illness Rating Scale (Substance Abuse version).

OBJECTIVE: To adapt the Cumulative Illness Rating Scale for its use in substance abuse patients (CIRS-SA) and to assess the reliability, internal consistency, and validity of the instrument. METHOD: One-hundred outpatients of both sexes, 62 men and 38 women, with a mean (SD) age of 32.4 (7.9) years (range 19-57), all of them fulfilling the DSM-IV criteria for any substance abuse disorder. Internal consistency was calculated with Cronbach's alpha coefficient. Test-retest and interrater reliability was assessed with the intraclass correlation coefficient and Wilcoxon z. Validity of the scale was assessed with Kendall's tau correlation coefficient. RESULTS: The final CIRS-SA version had a total of 13 items. Cronbach's alpha coefficient was 0.57. All intraclass correlation coefficients were above 0.7, and some items showed exact coincidence. The stability of the CIRS-SA scale in a 1-month test re-test reassessment was demonstrated. The CIRS-SA score showed a significant correlation with all consultant scores. CONCLUSION: CIRS-SA is a reliable and valid instrument to assess and to determine systematically the physical condition of substance abusers in whom infections, particularly by the HIV, are highly prevalent.