Search

The protective effect of estrogen replacement on ascending urinary-tract infection (UTI) is controversial. We designed a study using an experimental model of UTI in which surgically menopausal mice were supplemented with estrogen and the susceptibility to UTI was evaluated after experimental Escherichia coli infection. The mean rate of E. coli infection in the group not treated with estrogen was 2 x 10(4) cfu/g of renal tissue, compared with 9 x 10(8) cfu/g (P

Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens.

Septic shock, a major cause of death, is characterized by a pathophysiologic increased production of nitric oxide (NO), which leads to vasodilation and myocardial toxicity. Septic Escherichia coli frequently express proteinaceous curli fibers. In this study, curliated E. coli induced high levels of NO by directly inducing type 2 nitric oxide synthase (NOS2) both in vitro and in vivo. More severe hypotension and higher plasma nitrite/nitrate levels were seen in wild type mice systemically infected with curliated E. coli than in animals infected with E. coli mutants that lacked curli proteins. Blood pressure remained stable in NOS2-deficient mice with curliated bacteria. Increased heart rates, transient hypothermia, and loss of gross activity were seen in all mice, regardless of curli expression. Study results suggest that expression of curli fibers by E. coli activates the NO/NOS2 arm of the innate immune system, which leads to a significant fall in blood pressure.

Background. E5564, a competitive lipid A antagonist, inhibits endotoxin-stimulated inflammation and is under study in patients with sepsis. Methods. We tested whether clinically relevant variables, including the timing of treatment and the route of infection, influenced the effective dosing of E5564 in Escherichia coli-challenged rats. Results. All E5564 doses (0.3, 1.0, 2.0, and 3.0 mg/kg intravascular bolus followed by 10% of the bolus dose infused hourly for 24 h) administered 1 h before intravascular E. coli challenge similarly reduced the risk of death. Delaying the start of E5564 to 1 or 3 h after intravascular E. coli challenge significantly reduced the beneficial effect of the doses tested. However, increasing the dose of E5564 reversed some loss of efficacy for delayed treatment (P = .004, for increasing benefit with increasing dose at 1 h). During intrabronchial or intraperitoneal (extravascular) E. coli challenge, the pattern of effective E5564 dosing was the inverse of that for intravascular E. coli challenge (P = .001, for the interaction)-lower doses of E5564 were beneficial and higher doses were not (0.03, 0.3, 1.0, 2.0, and 3.0 mg/kg bolus followed by infusion) (P = .05, for decreasing benefit with increasing dose at 1 h). Conclusion. These findings suggest that, for maximal clinical benefit, E5564 should be given early and that dosing should be adjusted upward for intravascular infection and downward for extravascular infection.

In Escherichia coli infection, the implications of fluoroquinolone (FQ) and extended-spectrum cephalosporin plus cephamycin (AmpC) resistance for phylogenetic origin and virulence potential are undefined, as is the influence of ecological context on these associations. Accordingly, 106 E. coli isolates exhibiting FQ and/or AmpC resistance and 98 susceptible isolates were compared with regard to phylogenetic background and virulence profiles, stratified by host group (104 predominantly extraintestinal human isolates and 100 predominantly intestinal cattle and swine isolates). Although resistant isolates exhibited significant shifts in phylogenetic distribution and virulence profiles, human and animal isolates exhibited different phylogenetic shifts, and only among human isolates did resistance predict reduced virulence. Evidence for similar strains being resistant versus susceptible was scant. The O15:K52:H1 clonal group and the closely related "clonal group A" featured prominently among resistant and susceptible human isolates, respectively. Thus, in E. coli, antibiotic resistance predicts phylogenetic background and virulence potential in a complex, context-dependent fashion.