Asymmetric synthesis of enantiopure tetracyclic dispirooxindolopyrrolidine-piperidones via microwave-assisted multicomponent reaction: crystallographic analysis, antimicrobial activity and in silico studies

International audienceIn an attempt towards the development of new antimicrobials, we synthesized by microwave-assisted multicomponent reaction (MCR) of enantiopure (E,E)-3,5-bisarylidene-N-[(S)-(-)-methylbenzyl]-4-piperidones, isatin and α-amino esters a series of optically active tetracyclic dispirooxindolopyrrolidine-piperidones. The beneficial and promising features of this protocol such as simple operational procedure, short reaction time (10 min), and high product yields (up to 97%) make it an efficient eco-friendly approach offering a powerful mean to expand the structural diversity of spirooxindoles. This approach appears hugely advantageous for high-throughput screening processes in drug discovery research. In addition, crystallographic parameters and inter- and intramolecular interactions occurring in spiropyrrolidine-fused piperidone derivative 4g were examined through single-crystal XRD analysis allowing to determine the absolute configuration of the enantiopure compound. The preliminary biological assessment of their antimicrobial activity indicates that most of the screened products display higher activity than the standard reference drugs Ampicillin and Griseofulvin. Some of them exhibited good to moderate activity against both bacteria and fungi. In addition, in silico molecular docking and predictive ADMET studies for the most active spirocompounds were carried out. Molecular docking confirmed the binding efficacy of candidates 4c and 4l through low score energy values and the establishment of diverse bonding interactions with the active site residues. Finally, the ADMET profiling of the most active spiroheterocycles proved their remarkable drug-like and pharmacokinetic properties

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically

The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications. Methods: ASOS was a 7-day prospective cohort study of adult patients undergoing surgery in Africa. The ASOS Surgical Risk Calculator was constructed with a multivariable logistic regression model for the outcome of in-hospital mortality and severe postoperative complications. The following preoperative risk factors were entered into the model; age, sex, smoking status, ASA physical status, preoperative chronic comorbid conditions, indication for surgery, urgency, severity, and type of surgery. Results: The model was derived from 8799 patients from 168 African hospitals. The composite outcome of severe postoperative complications and death occurred in 423/8799 (4.8%) patients. The ASOS Surgical Risk Calculator includes the following risk factors: age, ASA physical status, indication for surgery, urgency, severity, and type of surgery. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.805 and good calibration with c-statistic corrected for optimism of 0.784. Conclusions: This simple preoperative risk calculator could be used to identify high-risk surgical patients in African hospitals and facilitate increased postoperative surveillance. © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Medical Research Council of South Africa gran