Over the 3-year study period, a total of 1,360 hospitalized patients were approached to enroll in the study. Of these patients, 789 (58.0%) provided consent and had a swab sample collected. As noted previously, there were no significant differences between eligible patients who enrolled in the study, compared with those who did not, except that participants were significantly older than nonparticipants (median age, 62 years vs 56 years).14
Of these 789 subjects, there were 15 who were included twice (ie, during surveillance sweeps in different years). Since only the first sample for each subject was included, a total of 774 unique subjects were included.
The median age among all 774 subjects was 62 years (interquartile range [IQR], 49–73 years), and 417 (53.9%) were male. Of the 774 total subjects, 446 (57.6%) were white, 273 (35.3%) were African-American, 9 (1.2%) were Asian, 5 (0.6%) were Latino, and 41 (5.3%) were of unknown race or ethnicity. Five hundred eighty-five patients (75.6%) were hospitalized at the Hospital of the University of Pennsylvania, and 189 (24.4%) were hospitalized at Penn Presbyterian Medical Center. At the time of study enrollment, the geographic locations of hospitalized subjects were as follows: medical floor, 245 (31.7%); surgical floor, 165 (21.3%); oncology floor, 89 (11.5%); medical and/or cardiac intensive care unit, 78 (10.1%); surgical intensive care unit, 63 (8.1%); rehabilitation floor, 42 (5.4%); transplantation floor, 39 (5.0%); neurology floor, 38 (4.9%); and obstetrics/gynecology, 15 (1.9%).
Of the 774 subjects, 89 (11.5%) were colonized with FQREC. By year, the prevalence of FQREC among fecal samples was: 15.9% (26 of 164) in 2002; 11.3% (39 of 346) in 2003; and 9.1% (24 of 264) in 2004 (P = .04, χ2 test for trend). Of note, the prevalence of FQ resistance among E. coli isolates in clinical cultures increased steadily at both hospitals during this same time period.
On bivariable analyses, several variables were noted to be significantly associated with FQREC colonization (). FQ use within the prior 30 days was associated with FQREC colonization (OR, 2.02 [95% CI, 1.14–3.46]; P = .01). Although the use of several other antibiotics was also associated with FQREC colonization, use of an agent with antianaerobic activity was not (OR, 0.99 [95% CI, 0.58–1.62]; P > .99). Furthermore, there was no association between overall antibiotic use and FQREC colonization; the median number of antibiotic days for case patients was 2 (IQR, 0–16 antibiotic days) and for control patients was 2 (IQR, 0–8.5 antibiotic days) (P = .30). Neither the Charlson score (P = .35) nor the number of days in the intensive care unit within the previous 30 days (P = .55) was associated with FQREC colonization.
Results of Bivariable Analysis of Risk Factors for Colonization With Fluoroquinolone-Resistant Escherichia coli
On stratified analysis, there was significant effect modification by year of study (P = .005), with a significant association between prior FQ use and FQREC colonization for subjects enrolled in 2004 but not for subjects enrolled in 2002 or 2003. The association between FQ use and FQREC colonization in the 3 study years was as follows: OR, 0.75 (95% CI, 0.17–2.47) in 2002; OR, 1.43 (95% CI, 0.53–3.43) in 2003; and OR, 6.68 (95% CI, 2.42–17.86) in 2004.
On multivariable analysis, prior FQ use remained an independent risk factor for FQREC colonization, but this association varied significantly by year of enrollment (). After controlling for the hospital and the duration of hospitalization prior to sampling, the association between FQ use and FQREC colonization was as follows: adjusted OR (aOR), 0.97 (95% CI, 0.29–3.23), P = .96, in 2002; aOR, 1.41 (95% CI, 0.57–3.50), P = .46, in 2003; and aOR, 9.87 (95% CI, 3.67–26.55), P < .001, in 2004.
Multivariable Model of Risk Factors for Colonization With Fluoroquinolone (FQ)–Resistant Escherichia coli
To explore possible explanations for the changes in the association between FQ use and FQREC colonization over time, we evaluated the potential impact of the underlying FQ resistance mechanism(s). The most common mechanism of FQ resistance in E. coli
is chromosomal mutation of the genes that encode the 2 FQ target enzymes (ie, DNA gyrase and topoisomerase IV).32,33
Another mechanism of FQ resistance is increased drug efflux via the AcrAB efflux pump.32,33
As noted previously, the resistance mechanism(s) of the FQREC isolates recovered from subjects included in this study were characterized as part of a previous descriptive molecular epidemiological study.14
In that study, it was noted that the proportion of isolates that demonstrated efflux overexpression as a mechanism of FQ resistance varied significantly across study years (ie, 48.6% in 2002, 47.7% in 2003, and 22.4% in 2004; P
= .01). To elucidate whether these temporal changes in underlying FQ resistance mechanisms might explain our findings of changes in risk factors over the same time period, we conducted 2 subanalyses in which case patients were divided on the basis of whether the colonizing isolate demonstrated efflux overexpression, as measured indirectly by the organic solvent tolerance assay.34,35
Case patients with FQREC isolates that exhibited efflux overexpression were compared with all control patients. Separately, case patients with FQREC isolates that did not exhibit efflux overexpression were compared with control patients. The results of the final multivariable models for both of these subanalyses did not differ substantively from the results of the primary model. For both models, FQ use remained a significant risk factor for FQREC colonization in 2004 only, after adjustment for the hospital and the duration of hospitalization prior to sampling.