Impact of antimicrobial stewardship programme on hospitalized patients at the intensive care unit: a prospective audit and feedback study

AIMS: Inappropriate use of antibiotics is one of the most important factors contributing to the emergence of drug resistant pathogens. The purpose of this study was to measure the clinical impact of antimicrobial stewardship programme (ASP) interventions on hospitalized patients at the Intensive care unit at Palestinian Medical Complex. METHODS: A prospective audit with intervention and feedback by ASP team within 48-72 h of antibiotic administration began in September 2015. Four months of pre-ASP data were compared with 4 months of post-ASP data. Data collected included clinical and demographic data; use of antimicrobials measured by defined daily doses, duration of therapy, length of stay, readmission and all-cause mortality. RESULTS: Overall, 176 interventions were made the ASP team with an average acceptance rate of 78.4%. The most accepted interventions were dose optimization (87.0%) followed by de-escalation based on culture results with an acceptance rate of 84.4%. ASP interventions significantly reduces antimicrobial use by 24.3% (87.3 defined daily doses/100 beds vs. 66.1 defined daily doses/100 beds P < 0.001). The median (interquartile range) of length of stay was significantly reduced post ASP [11 (3-21) vs. 7 (4-19) days; P < 0.01]. Also, the median (interquartile range) of duration of therapy was significantly reduced post-ASP [8 (5-12) days vs. 5 (3-9); P = 0.01]. There was no significant difference in overall 30-day mortality or readmission between the pre-ASP and post-ASP groups (26.9% vs. 23.9%; P = 0.1) and (26.1% vs. 24.6%; P = 0.54) respectively. CONCLUSIONS: Our prospective audit and feedback programme was associated with positive impact on antimicrobial use, duration of therapy and length of stay

Mood Disorder Due to a General Medical Condition with Manic Features

This case report describes a patient with manic and psychotic symptoms who had a history of neurocysticercosis and presented with an episode of hypertensive hydrocephalus in 2003. Despite her history, she was initially treated for primary psychiatric disease

Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis

Bacterial infections are the most prevalent etiological factors of epididymitis, a commonly diagnosed inflammatory disease in the investigation of male infertility factors. The influence of early pathogenic mechanisms at play during bacterial epididymitis on reproductive outcomes is little understood. We report here that experimental epididymitis induced in rats by Gram-negative (LPS) and Gram-positive (LTA) bacterial products resulted in differential patterns of acute inflammation in the cauda epididymis. LPS elicited a strong inflammatory reaction, as reflected by upregulation of levels of mRNA for seven inflammatory mediators (Il1b, Tnf, Il6, Ifng, Il10, Nos2 and Nfkbia), and tissue concentration of six cytokines/chemokines (IL1A, IL1B, IL6, IL10, CXCL2 and CCL2) within the first 24 h post-treatment. Conversely, LTA induced downregulation of one (Nfkbia) and upregulation of six (Il1b, Il6, Nos2, Il4 Il10 and Ptgs1) inflammatory gene transcripts, whereas increased the tissue concentration of three cytokines/chemokines (IL10, CXCL2 and CCL2). The stronger acute inflammatory response induced by LPS correlated with a reduction of epididymal sperm count and transit time that occurred at 1, 7, and 15 days post-treatment. Our study provides evidence that early epididymal inflammatory signaling events to bacterial activators of innate immunity may contribute to the detrimental effects of epididymitis upon male fertility.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)CNPqSao Paulo Research Foundation (FAPESP)Pro-Reitoria de Pesquisa/UNESPUniv Fed Sao Paulo, Escola Paulista Med, Sect Expt Endocrinol, Dept Pharmacol, BR-04044020 Sao Paulo, SP, BrazilUniv Estadual Paulista, Dept Pharmacol, Inst Biosci Botucatu, Botucatu, SP, BrazilSci & Innovat Ctr Androl, Androsci, BR-03178200 Sao Paulo, SP, BrazilUniv Sao Paulo, Med Sch, Hosp Clin, Reprod Toxicol Unity,Dept Pathol, BR-01246903 Sao Paulo, SP, BrazilUniv Sao Paulo, Med Sch, Hosp Clin, Div Urol, BR-01246903 Sao Paulo, SP, BrazilState Univ Centro Oeste, Dept Pharm, BR-85040080 Guarapuava, PR, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Sect Expt Endocrinol, Dept Pharmacol, BR-04044020 Sao Paulo, SP, Brazil(CNPq)/CSF/BJT: 401718/2012-3CNPq: 479546/2013-4, 455450/2014-5, 308349/2010-5FAPESP: 2010/52711-0, 2015/08227-0Pro-Reitoria de Pesquisa/UNESP: 557Web of Scienc

Potential health impact of ultrafine particles under clean and polluted urban atmospheric conditions: a model-based study

The main goal of this study was to improve the knowledge of ultrafine particle number distributions in large urban areas and also to call the attention to the importance of these particles on assessing health risks. Measurements of aerosol size distributions were performed during 2 weeks, with distinct pollutant concentrations (polluted and clean periods), on the rooftop of a building located in downtown of the megacity of São Paulo, Brazil. CO, NO2, PM10, SO2, and O3 concentrations and meteorological variables were also used. Aerosol size distribution measurements showed that geometric mean diameters of the size spectra in the polluted period are on average considerably larger than those in the clean one. Besides the fact that total number of ultrafine particles did not show significant differences, during the polluted period, geometric mean diameter was larger than during the clean one. The results of a mathematical model of particle deposition on human respiratory tract indicated a more significant effect of smaller particles fraction of the spectra, which predominate under clean atmospheric conditions. The results also indicated that urban environmental conditions usually considered good for air quality, under the criteria of low mass concentration, do not properly serve as air quality standard to very small particles. In the size range of ultrafine particles, this traditional clean atmospheric condition can offer a strong risk to pulmonary hazards, since the cleansing of the atmosphere creates good conditions to increase the concentration of nucleation mode particles

A False Case of Clozapine-Resistant Schizophrenia

One of the subjects that most concerns physicians is treatment-resistance. About 30%–60% of schizophrenia patients do not respond adequately to antipsychotic treatment and are known as refractory schizophrenia patients. Clozapine has been the drug of choice in such cases. However, approximately 30% of them do not respond to clozapine either. Here, we describe a patient with an initial diagnosis of refractory schizophrenia who had a history of dramatic aggressiveness. However, in this case, “refractoriness” was a wrong diagnosis. A case of psychosis secondary to epilepsy had been treated as schizophrenia for almost 20 years. Reports like this one are important because they remind us of how a thorough investigation can lead to the correct diagnosis and improve the patient's prognosis

Targeting Cellular Metabolism With CPI-613 Sensitizes Pancreatic Cancer Cells to Radiation Therapy

PURPOSE: Local tumor progression is a cause of significant morbidity and mortality in patients with pancreatic ductal adenocarcinoma (PDAC) with surgically unresectable disease. Novel and effective approaches to accomplish durable local control are urgently needed. We tested whether CPI-613 (devimistat), a first-in-class investigational small molecule inhibitor of mitochondrial metabolism, was capable of altering cancer cell energy metabolism and sensitizing PDAC cells to radiation therapy (RT). METHODS AND MATERIALS: The effect of a combined treatment of RT with CPI-613 on the viability of, clonogenic potential of, and cell death induction in PDAC cells (MiaPaCa-2 and Panc-1) was determined using a trypan blue dye exclusion assay, a colony formation assay, and a 7-amino-actinomycin D assay, respectively. The synergistic effects of CPI-613-RT and chemotherapeutic agents (gemcitabine or 5-fluorouracil) were measured in MiaPaCa-2 cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and spheroid formation assay. Changes in energy metabolism were determined by profiling metabolites treated with either RT, CPI-613, or both using liquid chromatography-mass spectrometry. RESULTS: This study demonstrates that a combination of single-fraction RT (2 and 10 Gy) with CPI-613 significantly inhibits PDAC cell growth compared with RT alone. Molecular analysis revealed inhibition of α-ketoglutarate dehydrogenase at the protein level. In addition, we demonstrate enhanced cell death of PDAC cells when treated with RT-CPI-613 combination. Targeted metabolomic analysis on PDAC cells post-CPI-613-RT treatment revealed alterations in key mitochondrial metabolites, with broader target engagement by the combination treatment, indicating the sensitization of CPI-613-treated PDAC cells to RT. Furthermore, a combination treatment of CPI-613 with either gemcitabine or 5-fluorouracil in the presence of 2 Gy RT synergistically inhibits PDAC cell proliferation. CONCLUSIONS: Our results support a novel combination of CPI-613-RT that warrants further preclinical and early-phase clinical investigations. A phase 1 trial designed to identify the maximum tolerated dose of CPI-613 in combination with chemo-RT in patients with PDAC was recently initiated (NCT05325281)