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Opioids are widely misused and account for almost half of overdose deaths in the United States. The cost in terms of lives, health care, and lost productivity is significant and has been declared a national crisis. Fentanyl is a highly potent mu opioid receptor (MOR) agonist and plays a significant role in the current opioid epidemic; fentanyl and its analogs (fentalogs) are increasingly becoming one of the biggest dangers in the opioid crisis. The availability of fentalogs in the illicit market is thought to play a significant role in the recent increase in opioid‐related deaths. Although there is both rodent homolog in vivo and in vitro data for some fentalogs, prior to this publication very little was known about the pharmacology of many of these illicit compounds at the human MOR (hMOR). Using gas chromatography–mass spectrometry, nuclear magnetic resonance spectroscopy, and in vitro assays, this study describes the spectral and pharmacological properties of 34 fentalogs. The reported spectra and chemical data will allow for easy identification of novel fentalogs in unknown or mixed samples. Taken together these data are useful for law enforcement and clinical workers as they will aid in the identification of fentalogs in unknown samples and can potentially be used to predict physiological effects after exposure. [ABSTRACT FROM AUTHOR]

Neutropenic enterocolitis ( NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia ( AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively ( P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality ( P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [ OR]: 0.109; 95% confidence interval [ CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome ( OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset. [ABSTRACT FROM AUTHOR]

Enterobacter aerogenes has recently emerged as an important hospital pathogen. In this study, we showed the emergence of E. aerogenes isolates carrying the bla KPC gene in patients colonized by carbapenem-resistant Klebsiella pneumoniae strains. Two multiresistant E. aerogenes isolates were recovered from bronchial aspirates of two patients hospitalized in the Intensive Care Unit at the 'Santa Maria della Scaletta' Hospital, Imola. The antimicrobial susceptibility test showed the high resistance to carbapenems and double-disk synergy test confirmed the phenotype of KPC and AmpC production. Other investigation revealed that ESBL and bla KPC genes were carried on the conjugative pKpQIL plasmid. This is a relevant report in Italy that describes a nosocomial infection due to the production of KPC beta-lactamases by an E. aerogenes isolate in patients previously colonized by K. pneumoniae carbapenem-resistant. In conclusion, it's necessary a continuous monitoring of multidrug-resistant strains for the detection of any KPC-producing bacteria that could expand the circulation of carbapenem-resistant pathogens. [ABSTRACT FROM AUTHOR]

Ureaplasma urealyticum is an opportunistic pathogen during pregnancy and in newborns. Other clinical problems related to U. urealyticum infections are: no susceptibility to cell wall-active drugs, limits of antibiotic treatment in pregnancy, and spread of antimicrobial resistance. In addition, the results of antimicrobial susceptibility against U. urealyticum from various countries are few and controversial. The antimicrobial susceptibility of U. urealyticum, isolated from cervical swabs and collected from outpatient childbearing-aged women in Italy from 2009 to 2012, was performed against fluoroquinolones, macrolides, streptogramin and tetracyclines, using an available biochemical commercial kit and a specific solid culture medium, to improve the therapeutic management of these pathogenic agents. Ureaplasma urealyticum was detected in 49.4% of samples, but significant bacterial load was revealed in 29.8%. In vitro tetracyclines showed the best activity against U. urealyticum, followed by streptogramin, macrolides, and fluoroquinolones. [ABSTRACT FROM AUTHOR]

Strains of Klebsiella pneumoniae producing KPC-carbapenemase have emerged as one of the most important multidrug-resistant Gram-negative nosocomial pathogens. Here, we report the first isolation and subsequent dissemination of a K. pneumoniae ST512 producing KPC-3 carbapenemase in a hospital in southern Italy. Isolates were obtained from blood, throat swabs, sputum, catheters, and urine of patients admitted to different hospital wards. Antimicrobial MICs were determined for all isolates by automated systems and confirmed by Etest. Carbapenemase production was confirmed by the modified Hodge test and by a disc synergy test, and carbapenemase genes were investigated by PCR. All isolates were characterized by pulse-field gel electrophoresis ( PFGE) and multilocus sequence typing ( MLST) analysis. Most isolates were multidrug resistant with exception of some isolates intermediately susceptible to gentamicin, tigecycline, and trimethoprim-sulfamethoxazole. PCR analysis showed that isolates harbored the blaKPC-3 gene associated with blaTEM and blaSVH. PFGE and MLST showed that all isolates belonged to the same ST512 clone recently described in Israel. [ABSTRACT FROM AUTHOR]

Neutrophils are essential players in acute inflammatory responses. Upon stimulation, neutrophils activate NADPH oxidase, generating an array of reactive oxygen species ( ROS). Interleukin-1 beta ( IL-1β) is a major proinflammatory cytokine synthesized as a precursor that has to be proteolytically processed to become biologically active. The role of ROS in IL-1β processing is still controversial and has not been previously studied in neutrophils. We report here that IL-1β processing in human neutrophils is dependent on caspase-1 and on the serine proteases elastase and/or proteinase 3. NADPH oxidase deficient neutrophils activated caspase-1 and did not exhibit differences in NALP3 expression, indicating that ROS are neither required for inflammasome activation nor for its priming, as has been reported for macrophages. Strikingly, ROS exerted opposite effects on the processing and secretion of IL-1β; whereas ROS negatively controlled caspase-1 activity, as reported in mononuclear phagocytes, ROS were found to be necessary for the exportation of mature IL-1β out of the cell, a role never previously described. The complex ROS-mediated regulation of neutrophil IL-1β secretion might constitute a physiological mechanism to control IL-1β-dependent inflammatory processes where neutrophils play a crucial role. [ABSTRACT FROM AUTHOR]