We describe a field investigation in New England that identified the emergence and epidemiology of new strains of multidrug-resistant Salmonella, Newport-MDRAmpC, and summarize the Center for Disease Control and Prevention's surveillance data for these infections. In Massachusetts, the prevalence of Newport-MDRAmpC among Salmonella serotype Newport isolates obtained from humans increased from 0% (0/14) in 1998 to 53% (32/60) in 2001 (P<.001). In a retrospective case-control study, infection with Newport-MDRAmpC was domestically acquired and was associated with exposure to a dairy farm. Isolates from both humans and cattle had indistinguishable or closely related antibiograms and pulsed-field gel electrophoresis patterns. Nationally, the prevalence of ceftriaxone-resistant Salmonella increased from 0.5% in 1998 to 2.4% in 2001; 85% of the isolates in 2001 were Newport-MDRAmpC, and at least 27 states have isolated these strains from humans, cattle, or ground beef. These data document the widespread emergence of Newport-MDRAmpC strains in the United States and show that the 5-fold increase in the prevalence of Salmonella resistant to expanded-spectrum cephalosporins, between 1998 and 2001, is primarily due to the emergence of Newport-MDRAmpC strains.
For Salmonella enterica serovar Enteritidis, 85% of isolates can be classified into 5 pulsed-field gel electrophoresis (PFGE) types. However, PFGE has limited discriminatory power for outbreak detection. Although whole-genome sequencing has been found to improve discrimination of outbreak clusters, whether this procedure can be used in real-time in a public health laboratory is not known. Therefore, we conducted a retrospective and prospective analysis. The retrospective study investigated isolates from 1 confirmed outbreak. Additional cases could be attributed to the outbreak strain on the basis of whole-genome data. The prospective study included 58 isolates obtained in 2012, including isolates from 1 epidemiologically defined outbreak. Whole-genome sequencing identified additional isolates that could be attributed to the outbreak, but which differed from the outbreak-associated PFGE type. Additional putative outbreak clusters were detected in the retrospective and prospective analyses. This study demonstrates the practicality of implementing this approach for outbreak surveillance in a state public health laboratory.
Individual or multiple resistance to clindamycin, tetracycline, erythromycin, levofloxacin, or mupirocin was detected in a large proportion of methicillin-resistant Staphylococcus aureus pulsed-field type USA300 isolates collected at an ambulatory health center in Boston. The clindamycin, tetracycline, and mupirocin resistance genes identified in these isolates are commonly associated with plasmids.
The family Paramyxoviridae comprises a diverse group of viruses that includes several important human and veterinary pathogens. Members of this family have a non-segmented, single-stranded, negative sense RNA genome, a conserved gene order, and a similar replication strategy. Paramyxoviruses are divided into two subfamilies, Paramyxovirinae and Pneumovirinae, which comprise five genera and two genera, respectively. Viruses in each genus have developed strategies to circumvent the interferon (IFN) response by using a diverse array of proteins that are encoded within the phosphoprotein genes of the Paramyxovirinae or non-structural genes of the Pneumovirinae. This review focuses on the specific roles that these viral proteins play in the inhibition of IFN signaling and, to a lesser extent, on the mechanisms by which these proteins inhibit the induction pathways of IFN. An improved understanding of the interactions between viral proteins and the host innate immune response is critical to achieving a thorough comprehension of the pathogenesis of this important group of viruses. Hopefully this knowledge will support the development of more targeted vaccines and therapeutics to better prevent and control viral infection.
The C and V proteins of the measles virus (MV) have been shown to block the signaling of type I and II interferon (IFN-alpha/beta and IFN-gamma). The relative contribution of the C and V proteins to the inhibition of IFN signaling and the extent to which this activity differs in attenuated or wild-type strains of MV remains undefined. This study presents a comparison of the IFN-antagonist activities of C and V proteins from four attenuated and two wild-type strains of MV. The V proteins were more potent inhibitors of IFN-inducible reporter gene expression than the C proteins, and this effect was unrelated to whether the protein originated from an attenuated or wild-type strain. The results also demonstrated the importance of the tyrosine at position 110 in the inhibition of IFN-alpha/beta and IFN-gamma signaling by the V protein, and identified a non-recombinant MV expressing a V protein that was impaired due to a mutation at this residue.
Background-Intravenous administration of some liposomal drugs can trigger immediate hypersensitivity reactions that include symptoms of cardiopulmonary distress. The mechanism underlying the cardiovascular changes has not been clarified. Methods and Results-Anesthetized pigs (nϭ18) were injected intravenously with 5-mg boluses of large multilamellar liposomes, and the ensuing hemodynamic, hematologic, and laboratory changes were recorded. The significant (PϽ0.01) alterations included 79Ϯ9% (meanϮSEM) rise in pulmonary arterial pressure, 30Ϯ7% decline in cardiac output, 11Ϯ2% increase in heart rate, 236Ϯ54% increase in pulmonary vascular resistance, 71Ϯ27% increase in systemic vascular resistance, and up to a 100-fold increase in plasma thromboxane B 2 . These changes peaked between 1 and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose-dependent (ED 50 ϭ4.5Ϯ1.4 mg), and were quantitatively reproducible in the same animal several times over 7 hours. The liposome-induced rises of pulmonary arterial pressure showed close quantitative and temporal correlation with elevations of plasma thromboxane B 2 and were inhibited by an anti-C5a monoclonal antibody (GS1), by sCR1, or by indomethacin. Liposomes caused C5a production in pig serum in vitro through classic pathway activation and bound IgG and IgM natural antibodies. Zymosan-and hemoglobin-containing liposomes and empty liposomes caused essentially identical pulmonary changes. Conclusions-The intense, nontachyphylactic, highly reproducible, complement-mediated pulmonary hypertensive effect of minute amounts of intravenous liposomes in pigs represents a unique, unexplored phenomenon in circulation physiology. The model provides highly sensitive detection and study of cardiopulmonary side effects of liposomal drugs and many other pharmaceutical products due to "complement activation-related pseudoallergy" (CARPA).
Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate was infused 1 h before (1 g. kg(-1). h(-1)) and 2 h during (0.5 g. kg(-1). h(-1)) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruvate group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.
Pyruvate (PYR) improves cellular and organ function hypoxia and ischemia by stabilizing the reduced nicotinamide adenine dinucleotide redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on neocortical function, indexes of the cytosolic redox state, cellular energy state, and ischemia during a prolonged (4 h) controlled arterial hemorrhage (40 mmHg) in swine. Thirty minutes after the onset of hemorrhagic shock, sodium PYR (n = 8) was infused (0.5 g x kg(-1) x h(-1)) to attain arterial levels of 5 mM. The volume and osmotic effects were matched with 10% NaCl [hypertonic saline (HTS)] (n = 8) or 0.9% NaCl [normal saline (NS)] (n = 8). During the hemorrhage protocol, the time to peak hemorrhage volume was significantly delayed in the PYR group compared with the HTS and NS groups (94 +/- 5 vs. 73 +/- 6 and 72 +/- 4 min, P < 0.05). In addition to the early onset of the decompensatory phase of hemorrhagic shock, the complete return of the hemorrhage volume during decompensatory shock resulted in the death of five and four animals, respectively, in the HTS and NS groups. In contrast, in the PYR group, reinfusion of the hemorrhage volume was slower and all animals survived the 4-h hemorrhage protocol. During hemorrhage, the PYR group also exhibited improved cerebral cortical metabolic and function status. PYR slowed and reduced the rise in neocortical microdialysis levels of adenosine, inosine, and hypoxanthine and delayed the loss of cerebral cortical biopsy ATP and phosphocreatine content. This improvement in energetic status was evident in the improved preservation of the electrocorticogram in the PYR group. PYR also prevented the eightfold increase in the excitotoxic amino acid glutamate observed in the HTS group. The findings show that PYR administered after the onset of hemorrhagic shock markedly improves cerebral metabolic and functional status for at least 4 h.
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