The emergence of resistance to the fluoroquinolone (FQ) class of antibiotics is an issue of great concern. Although FQ resistance is particularly worrisome for Escherichia coli, the most common gram-negative pathogen, the epidemiology of FQ-resistant E. coli (FQR-EC) has not been well described. Based on existing data, one may conceptualize three stages in the biological evolution of FQR-EC in a given individual: 1) acquisition of new FQR-EC fecal colonization; 2) persistence of FQR-EC fecal colonization; and 3) development of clinically apparent FQR-EC infection. The primary reason to conceptualize different stages of the evolution of FQR-EC is to increase the sensitivity in identifying critical components of the pathway that can be interrupted or manipulated clinically. Failure to recognize the distinct importance of these stages has limited the ability of past efforts to elucidate the epidemiology of FQR-EC because risk factors for the various stages likely differ, and because not all forms of FQR-EC colonization are equally likely to progress to infection due to differences in underlying FQ resistance mechanisms. Focusing on the progression from FQR-EC colonization to FQR-EC infection is critical for several reasons: 1) although E. coli colonizing the gastrointestinal (GI) tract serve as the primary source of E. coli that subsequently manifest as clinical infection, not all individuals colonized with FQR-EC develop FQR-EC infection; and 2) specifically isolating those risk factors that are associated with progression from colonization to infection are vital given the ultimate goal of identifying modifiable factors that will limit the occurrence of clinical FQR-EC infection. To date, risk factors for FQR-EC infection in patients colonized with FQR-EC have not been investigated. Investigating risk factors for prolonged FQR-EC fecal colonization is also essential for several reasons: 1) it is likely that the longer a patient remains FQR-EC colonized, the greater the likelihood of developing FQR-EC infection; and 2) humans are a major reservoir for E. coli and the GI tract may serve as the primary source from which FQR-EC can disseminate through the population. Risk factors for prolonged FQR-EC colonization have not been studied. The primary aims of this study are 1) to identify risk factors for progression from FQR-EC fecal colonization to clinical FQR-EC infection; and 2) to identify risk factors for prolonged FQR-EC fecal colonization. The primary hypotheses are that outpatient antimicrobial use and presence of efflux pump overexpression (as a mechanism of FQ resistance) are associated with both clinical FQR-EC infection and prolonged FQR-EC colonization. Elucidation of forces driving the emergence of clinical FQR-EC, particularly the relationship between clinical risk factors and FQ resistance mechanisms, is critical if efforts to limit the clinical impact of FQR-EC are to be successful. ? ?
| Greenblatt, Rachel M; Han, Jennifer H; Nachamkin, Irving et al. (2013) Defining relatedness in studies of transmission of antimicrobial-resistant organisms: variability in definitions across studies and impact of different approaches on study conclusions. Infect Control Hosp Epidemiol 34:40-8 |
| Han, Jennifer H; Nachamkin, Irving; Tolomeo, Pam et al. (2012) Risk factors for efflux pump overexpression in fluoroquinolone-resistant Escherichia coli. J Infect Dis 206:1597-603 |
| Lautenbach, Ebbing; Metlay, Joshua P; Mao, Xiangqun et al. (2010) The prevalence of fluoroquinolone resistance mechanisms in colonizing Escherichia coli isolates recovered from hospitalized patients. Clin Infect Dis 51:280-5 |
