Model-based estimates were broadly consistent with other sources of information on the HCV epidemic in Australia. These models suggest that the prevalence of HCV-related cirrhosis and the incidence of HCV-related liver failure and HCC will more than triple in Australia by 2020.

Sequencing of DNA from 15 expanded-spectrum cephalosporin (e.g., ceftriaxone)-resistant Salmonella isolates obtained in the United States revealed that resistance to ceftriaxone in all isolates was mediated by cmy-2. Hybridization patterns revealed three plasmid structures containing cmy-2 in these 15 isolates. These data suggest that the spread of cmy-2 among Salmonella strains is occurring through mobilization of the cmy-2 gene into different plasmid backbones and consequent horizontal transfer by conjugation.Salmonellosis is primarily a food-borne disease that affects an estimated 1.4 million people each year in the United States (14). Expanded-spectrum cephalosporins (e.g., ceftriaxone and cefotaxime) are the antimicrobial agents of choice in the treatment of pediatric patients with invasive Salmonella infections (9). Until recently, resistance to expanded-spectrum cephalosporins was rarely reported among Salmonella strains (8). Review of 1996 data from the National Antimicrobial Resistance Monitoring System (NARMS) in the United States identified only 1 (0.1%) ceftriaxone-resistant Salmonella isolate among 1,272 human Salmonella isolates. However, by 1999 almost 2% of Salmonella isolates were ceftriaxone resistant, as determined by review of 1999 NARMS data (6). Comparisons of these ceftriaxone-resistant isolates found divergent strains, indicating multiple probable sources. The isolates either were different serotypes or, among patients infected with Salmonella enterica serotype Typhimurium, were distinguishable by their pulsedfield gel electrophoresis patterns, thus demonstrating that these ceftriaxone-resistant human isolates did not represent the epidemic spread of a clonal strain (6). This study was undertaken to confirm the identity of the ␤-lactamase conferring resistance to expanded-spectrum cephalosporins and characterize the associated plasmids from the apparently sporadic human Salmonella isolates collected through NARMS from 1996 to 1998. MATERIALS AND METHODSThe 15 bacterial strains used in the study are listed in Table 1. Thirteen of the isolates were obtained by the Centers for Disease Control and Prevention through NARMS. These 13 isolates represented 87% of the total expandedspectrum cephalosporin-resistant Salmonella isolates (n ϭ 15) obtained by the Centers for Disease Control and Prevention from 1996 to 1998 (6). Isolate SS034 was isolated in Nebraska, whereas isolate 922 was isolated in Ohio. Susceptibility testing of the Salmonella isolates and the Escherichia coli transconjugants and transformants was performed by the disk diffusion methodology according to NCCLS standards (16). The MIC for the pACYC184 construct containing cmy-2 was tested by the E-test (AB Biodisk, Solna, Sweden) methodology. The MICs of ceftiofur (kindly provided by Pharmacia/Upjohn) were determined by broth microdilution (15, 17). Plasmid DNA was extracted either by the method of Kado and Liu (10) or with the Concert Purification Midi kit (Life Technologies, Milan, Italy) and digested with PstI (Roche, Indianapoli...

The emergence in the United States of resistance to expanded-spectrum cephalosporin (e.g., ceftriaxone) within the salmonellae has been associated primarily with three large (>100-kb) plasmids (designated types A, B, and C) and one 10.1-kb plasmid (type D) that carry the bla CMY-2 gene. In the present study, the distribution of these four known bla CMY-2 -carrying plasmids among 35 ceftriaxone-resistant Salmonella isolates obtained from 1998 to 2001 was examined. Twenty-three of these isolates were Salmonella enterica serotype Newport, 10 were Salmonella enterica serotype Typhimurium, 1 was Salmonella enterica serotype Agona, and 1 was Salmonella enterica serotype Reading. All 23 serotype Newport isolates carried a type C plasmid, and 5, 4, and 1 serovar Typhimurium isolate carried type B, A, and C plasmids, respectively. Both the serotype Agona and serotype Reading isolates carried type A plasmids. None of the isolates carried a type D plasmid. Hybridization data suggested that plasmid types A and C were highly related replicons. DNA sequencing revealed that the region surrounding bla CMY-2 was highly conserved in all three plasmid types analyzed (types B, C, and D) and was related to a region surrounding bla CMY-5 from the Klebsiella oxytoca plasmid pTKH11. These findings are consistent with a model in which bla CMY-2 has been disseminated primarily through plasmid transfer, and not by mobilization of the gene itself, to multiple Salmonella chromosomal backbones.

Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to determine critical disease parameters associated with disease progression, and establish correlations between primate and human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation.

Production of biofilm in Staphylococcus epidermidis is mediated through enzymes produced by the four-gene operon ica and is subject to phenotypic variation. The purpose of these experiments was to investigate the regulation of ica and icaR transcription in phenotypic variants produced by multiple unrelated isolates of S. epidermidis. Ten isolates were chosen for the study, four of which contained IS256. IS256 mediates a reversible inactivation of ica in approximately 30 % of phenotypic variants. All ten strains produced at least two types of phenotypic variant (intermediate and smooth) in which biofilm formation was significantly impaired. Reversion studies indicated that all phenotypic variants were stable after overnight growth, but began to revert to other phenotypic forms after 5 days of incubation at 37 8C. ica transcriptional analysis was performed on phenotypic variants from three IS256-negative isolates; 1457, SE5 and 14765. This analysis demonstrated that ica transcription was significantly reduced in the majority of phenotypic variants, although two variants from SE5 and 1457 produced wild-type quantities of ica transcript. Analysis of seven additional phenotypic variants from SE5 revealed that ica expression was only reduced in three. Expression of icaR transcript was unaffected in all smooth phenotypic variants. Mutations within ica were identified in two SE5 variants with wild-type levels of ica transcription. It is concluded that mutation and transcriptional regulation of ica are the primary mechanisms that govern phenotypic variation of biofilm formation within IS256-negative S. epidermidis.