Effect of parenteral antibiotic administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract.
ABSTRACT A mouse model of vancomycin-resistant Enterococcus faecium (VRE) intestinal colonization was used to study the effect of different subcutaneous antibiotics on persistence and density of VRE colonization. Gastric inoculation of a clinical VanB VRE isolate, in conjunction with oral vancomycin in drinking water (250 microgram/mL), resulted in high-level VRE colonization (mean, 9.5 log10 cfu/g) in all 169 experimental mice. After discontinuation of oral vancomycin, the level of VRE in the stool specimens of mice receiving subcutaneous saline steadily decreased (mean, 3.59 log10 cfu/g at day 19). Subcutaneous vancomycin, clindamycin, piperacillin-tazobactam, ticarcillin-clavulanic acid, metronidazole, cefotetan, ampicillin, and ampicillin-sulbactam all promoted persistent high levels of stool VRE. Subcutaneous ceftriaxone, cefepime, ciprofloxacin, and aztreonam promoted increased VRE density to a lesser degree or not at all. Thus, in a mouse model, vancomycin and antibiotics with potent antianaerobic activity promoted persistent high-density intestinal VRE colonization, whereas antibiotics lacking potent antianaerobic activity did not.
Article: Risk factors for colonization with extended-spectrum beta-lactamase-producing bacteria and intensive care unit admission.[show abstract] [hide abstract]
ABSTRACT: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are emerging pathogens. To analyze risk factors for colonization with ESBL-producing bacteria at intensive care unit (ICU) admission, we conducted a prospective study of a 3.5-year cohort of patients admitted to medical and surgical ICUs at the University of Maryland Medical Center. Over the study period, admission cultures were obtained from 5,209 patients. Of these, 117 were colonized with ESBL-producing Escherichia coli and Klebsiella spp., and 29 (25%) had a subsequent ESBL-positive clinical culture. Multivariable analysis showed the following to be statistically associated with ESBL colonization at admission: piperacillin-tazobactam (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.36-3.10), vancomycin (OR 2.11, 95% CI 1.34-3.31), age > 60 years (OR 1.79, 95% CI 1.24-2.60), and chronic disease score (OR 1.15; 95% CI 1.04-1.27). Coexisting conditions and previous antimicrobial drug exposure are thus predictive of colonization, and a large percentage of these patients have subsequent positive clinical cultures for ESBL-producing bacteria.Emerging infectious diseases 08/2007; 13(8):1144-9. · 6.17 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: The analysis of nosocomial infection data for communicable pathogens is complicated by two facts. First, typical pathogens more commonly cause asymptomatic colonization than overt disease, so transmission can be only imperfectly observed through a sequence of surveillance swabs, which themselves have imperfect sensitivity. Any given set of swab results can therefore be consistent with many different patterns of transmission. Second, data are often highly dependent: the colonization status of one patient affects the risk for others, and, in some wards, repeated admissions are common. Here, the authors present a method for analyzing typical nosocomial infection data consisting of results from arbitrarily timed screening swabs that overcomes these problems and enables simultaneous estimation of transmission and importation parameters, duration of colonization, swab sensitivity, and ward- and patient-level covariates. The method accounts for dependencies by using a mechanistic stochastic transmission model, and it allows for uncertainty in the data by imputing the imperfectly observed colonization status of patients over repeated admissions. The approach uses a Markov chain Monte Carlo algorithm, allowing inference within a Bayesian framework. The method is applied to illustrative data from an interrupted time-series study of vancomycin-resistant enterococci transmission in a hematology ward.American journal of epidemiology 09/2008; 168(5):548-57. · 5.59 Impact Factor
Article: Mechanisms of resistance and clinical relevance of resistance to β-lactams, glycopeptides, and fluoroquinolones.[show abstract] [hide abstract]
ABSTRACT: The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the β-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, β-lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired β-lactamases presents a particular challenge owing to some natural spectra that include virtually all β-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express β-lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria.Mayo Clinic Proceedings 02/2012; 87(2):198-208. · 5.70 Impact Factor