SummaryIron, an essential nutrient for most microorganisms, is sequestered by the host to decrease the concentration of iron available to bacterial pathogens. Neisseria gonorrhoeae, the causative agent of gonorrhoea, can acquire iron by direct interaction with human ironbinding proteins, including the serum glycoprotein, transferrin. Iron internalization from host transferrin requires the expression of a bacterial receptor, which specifically recognizes the human form of transferrin. Two gonococcal transferrin-binding proteins have been implicated in transferrin receptor function, TbpA and TbpB. We constructed a gonococcal transferrin receptor mutant without the introduction of additional antibiotic resistance markers and tested its ability to cause experimental urethritis in human male volunteers. The transferrin receptor mutant was incapable of initiating urethritis, although the same inoculum size of the wild-type parent strain, FA1090, causes urethritis in >90% of inoculated volunteers. To our knowledge, this is the first experimental demonstration that a bacterial iron acquisition system is an essential virulence factor for human infection.
Streptococcus pneumoniae strains have exhibited decreasing susceptibility to penicillins and macrolides during the past several years. We reviewed the medical charts of all patients with pneumococcal bacteremia who were admitted to a university hospital over a period of 1 year, to identify failures of outpatient therapy. Of 41 patients admitted with pneumococcal bacteremia, 4 had previously taken either azithromycin or clarithromycin for 3-5 days. All 4 had pneumococcal strains that exhibited low-level resistance to macrolide antibiotics. Among pneumococci, low-level resistance to macrolides can lead to clinical failure, and resistance to macrolides should be considered during the selection of empiric therapy for patients with presumed pneumococcal infections.
We conducted a multicenter, retrospective cohort study of patients with Streptococcus pneumoniae bacteremia to determine factors associated with antibiotic resistance and mortality. Risk factors were identified using multivariate logistic regression. 1,574 patients at 34 sites were enrolled. Compared to isolates from patients not receiving an antibiotic before the index blood culture, patients receiving an antibiotic were less likely to harbor an antibiotic susceptible organism. Susceptibility to penicillin decreased from 78% (95% confidence interval [CI], 75−80) to 49% (95%CI, 39−59); to cefotaxime/ ceftriaxone, from 92% (95%CI, 90−93) to 82% (95%CI, 72−89); and to macrolide, from 84% (95% CI, 82−87) to 55% (95%CI, 41−68). Factors associated with macrolide non-susceptibility include: >24 hours of antibiotic therapy at time of the index culture (odds ratio [OR] 4.0), residing in southern U.S. (OR 1.7), and having an antibiotic allergy (OR 1.7). Harboring an antibiotic non-susceptible strain (OR 1.4) and male sex (OR 1.4) were associated with increased risk of mortality, whereas Black race (OR 0.6) and evidence of focal infection (OR 0.6) were associated with decreased risk.
Antimicrobial resistance to penicillin and macrolides in Streptococcus pneumoniae has increased in the United States over the past decade. Considerable geographic variation in susceptibility necessitates regional resistance tracking. Traditional active surveillance is labor intensive and costly. We collected antibiogram reports from North Carolina hospitals and assessed pneumococcal susceptibility to multiple agents from 1996 through 2000. Susceptibility in North Carolina was consistently lower than the national average. Aggregating antibiogram data is a feasible and timely method of monitoring regional susceptibility patterns and may also prove beneficial in measuring the effects of interventions to decrease antimicrobial resistance.
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