Comparative activity of meropenem in US medical centers (2007): initiating the 2nd decade of MYSTIC program surveillance

Since 1997, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum agents against pathogens from hospitalized patients. In the United States, 2894 isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae, 643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All isolates were tested by broth microdilution methods. Meropenem (MIC(90) range, 0.12-2 microg/mL) exhibited the lowest resistance rates (1.9-2.4%) against Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance (17.3-18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli. Confirmed extended-spectrum beta-lactamase-producing isolate rates for E. coli, Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%, respectively. Meropenem remained active against Gram-positive pathogens such as staphylococci (methicillin-susceptible; MIC(90), 0.12-0.25 microg/mL), Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel beta-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.     

Trauma education and assessment

Trauma education has evolved over the past 30 years from an unstructured preceptorship to standardised courses offered worldwide. The Advanced Trauma Life Support (ATLS) course has formed the backbone of trauma management philosophy and has spawned a series of courses aimed at specific patient populations and health care groups. Trauma education and assessment for advanced trainees has taken the form of formal clinical fellowships. In addition to clinical experience, a number of tools have been validated in aiding trauma education including use of videotape review and simulation technology. Future emphasis on development and validation of teaching and assessment techniques could improve trauma education and secondarily impact trauma outcomes worldwide.     

Data mining of NCI's anticancer screening database reveals mitochondrial complex I inhibitors cytotoxic to leukemia cell lines

Mitochondria are principal mediators of apoptosis and thus can be considered molecular targets for new chemotherapeutic agents in the treatment of cancer. Inhibitors of mitochondrial complex I of the electron transport chain have been shown to induce apoptosis and exhibit antitumor activity. In an effort to find novel complex I inhibitors which exhibited anticancer activity in the NCI's tumor cell line screen, we examined organized tumor cytotoxicity screening data available as SOM (self-organized maps) (http://www.spheroid.ncifcrf.gov) at the developmental therapeutics program (DTP) of the National Cancer Institute (NCI). Our analysis focused on an SOM cluster comprised of compounds which included a number of known mitochondrial complex I (NADH:CoQ oxidoreductase) inhibitors. From these clusters 10 compounds whose mechanism of action was unknown were tested for inhibition of complex I activity in bovine heart sub-mitochondrial particles (SMP) resulting in the discovery that 5 of the 10 compounds demonstrated significant inhibition with IC50's in the nM range for three of the five. Examination of screening profiles of the five inhibitors toward the NCI's tumor cell lines revealed that they were cytotoxic to the leukemia subpanel (particularly K562 cells). Oxygen consumption experiments with permeabilized K562 cells revealed that the five most active compounds inhibited complex I activity in these cells in the same rank order and similar potency as determined with bovine heart SMP. Our findings thus fortify the appeal of mitochondrial complex I as a possible anticancer molecular target and provide a data mining strategy for selecting candidate inhibitors for further testing.     

Evaluation of Intensive Adjuvant Chemotherapy in Gastric Cancer Using Life Expectancy Compared with Log-Rank Test as a Measure of Survival Benefit

BACKGROUND: The goal of radical cancer surgery with or without adjuvant therapy is to cure disease rather than to delay death. There is concern that the survival benefit of curative treatment may not be properly appreciated by the log-rank test (LRT), which is more sensitive to treatment that delays death than to treatment that achieves cure. To confirm this concern and to evaluate the survival benefit of adjuvant chemotherapy, the data from a previous randomized controlled trial are analyzed using both traditional and new methods. METHODS: In this trial, 1410 gastric cancer patients with serosal or subserosal invasion had been classified by nodal and serosal status into four strata and randomized to receive high-dose or low-dose adjuvant regimens (mitomycin and tegafur-uracil) after gastrectomy. The two treatment groups were compared using the LRT as well as the life expectancy (LE) derived from the Boag model and the competing risk model. RESULTS: The LRT showed no significant difference between the two groups, whereas the LE increased significantly with high-dose chemotherapy (1.4-year gain; 95% CI = 0.1-2.8). A greater gain of 4.4 years occurred exclusively in the serosa-negative node-positive stratum, associated with a 21% increase in cure rate. The gain in LE was particularly greater in younger patients. CONCLUSIONS: Parametric LE analysis offers more relevant information about curative treatment than LRT. It suggests that high-dose chemotherapy may achieve cure in a subset of patients, eradicating residual malignancies left behind after gastrectomy and providing greater survival benefit than expected from LRT.     

Age-related cataract in dogs: a biomarker for life span and its relation to body size

Clinical data from 72 dog breeds of varying size and life expectancy were grouped according to breed body mass and tested for prevalence at ages 4 to 5, ages 7 to 10, and lifetime incidence of non-hereditary, age-related cataract (ARC). The incidence of ARC was found to be directly related to the relative life expectancies in the breed groups: The smallest dog breeds had a lower ARC prevalence between ages 4 and 5 than mid-size breeds and these, in turn, a lower prevalence than the giant breeds. A similar sequence was evident for ages 7 to 10 and for overall lifetime incidence of ARC. These differences became more significant when comparing small and giant breeds only. We could also confirm the inverse relationship between body size and life expectancy in these same sets of dog breeds. Our results show that body size, life expectancy, and ARC incidence are interrelated in dogs. Given that ARC has been shown to be at least partially caused by oxidative damage to lens epithelial cells and the internal lens, we suggest that it can be considered not only as a general biomarker for life expectancy in the canine and possibly other species, but also for the systemic damages produced by reactive oxygen species. This suggests new approaches to examine the gene expression pathways affecting the above-noted linkages.     

Changes in injection risk behavior associated with participation in the seattle needle-exchange program

We studied the influence of the Seattle, Washington, needle-exchange program on sharing of drug injection equipment (syringes, drug cookers, filtration cotton) to identify potential gaps in risk reduction and to understand in greater detail the lack of an association between exchange use and risk of hepatitis B or C virus transmission. In a cohort of 2,208 injection drug users who completed a 1-year follow-up visit, we measured the association between needle-exchange use at study enrollment (ever vs. never) and injection risk behavior at the follow-up. Control for confounding was carried out using both logistic regression and propensity score analytic methods to estimate the adjusted odds ratio (AOR). In both univariate and multivariate analyses ,needle-exchange use was associated with a lower likelihood of injection with a used syringe (AOR-0.7,95% confidence limit 0.5,0.9). There was no association between exchange use and cooker or cotton sharing (AOR-0.8,95% confidence limit 0.6, 1.1) or between exchange use and use of a common syringe to divide drugs (AOR=0.9). This analysis suggests that risk reduction measures adopted by users of the Seattle exchange may not be sufficient to prevent transmission of all blood-borne viruses, including hepatitis C virus. Creater awareness of the infection risk associated with these practices may help curb this type of equipment sharing and ultimately prevent disease transmission.