In this retrospective cohort study involving nearly 300 consecutive patients with extraintestinal E. coli infection, we found ST131 to be a dominant, antimicrobial-resistant clonal group associated with healthcare, elderly hosts, and persistent or recurrent symptoms. Specifically, we found that ST131 infection was associated with older age, LTCF residence, complex infection, a history of UTI, previous antimicrobial use, receipt of more than 1 antibiotic within 30 days after diagnosis, and having recurrent or persistent symptoms after therapy. In addition, we found a high prevalence of 2 predominant PFGE types among the ST131 isolates, which suggests that our region, like others in the United States, is experiencing the global ST131 pandemic.
In our cohort, ST131 isolates were more than twice as common among healthcare-associated infections as they were among community-associated infections. This suggests that, in our area, ST131 is primarily a healthcare-associated clonal group. This conflicts with the many studies that have identified ST131, especially when harboring ESBL genes, as community-associated.11,19,20
This discrepancy likely stems from differences in sample type and collection, because our isolates were collected consecutively, were not selected on the basis of patient or pathogen characteristics, and included few ESBL-producing strains, whereas in other studies, isolates were often selected on the basis of specific resistance phenotypes or patient characteristics. Alternatively, geographic variation may exist in the relative prevalence of ST131 between hospital and community settings.
In our cohort, LTCF residence was the strongest predictor of ST131 infection, with LTCF residents having 8-fold greater multivariable odds of having ST131 compared with non-LTCF residents. Although a LTCF reservoir for ST131 has been noted previously,21–24
our data are the first, to our knowledge, to demonstrate that LTCF residence is a risk factor for ST131 in the United States. LTCFs are well-known sources for other antimicrobial-resistant pathogens23,25–28
and for outbreaks in acute care hospitals and other settings.29–31
The increasing prevalence of ST131 that we observed among patients older than 65 years is consistent with the association of ST131 with LTCFs. It is likely that extensive antibiotic exposure, close contact with other antibiotic-exposed individuals, and age- and health-associated alterations in intestinal microbiota32
all contribute to the high prevalence of ST131 among the elderly population.
Cure rates and mortality did not differ between patients with ST131 versus non-ST131 infections after adjustment for host characteristics such as age and LTCF residence, which suggests that ST131 is not more virulent, on average, than non-ST131 E. coli
. This is supported by recent in vivo studies that found no difference in experimental virulence between ST131 and other extraintestinal E. coli
Similarly, no difference in mortality associated with ST131 versus non-ST131 was seen in a recent study of patients with ESBL E. coli
However, here ST131 was associated with having recurrent or persistent symptoms, which is likely attributable to receiving inappropriate empirical therapy. Among patients with ST131, of whom 40% had received a FQ in the recent past, a quarter received empirical treatment with FQs, which are largely ineffective against this clonal group, and required a change in antibiotic regimen after culture and susceptibility results became available. This phenomenon doubtless contributed to the greater number of antibiotics received by patients with ST131 infection compared with non-ST131 infection. This suggests that many prescribers are unaware of the increasing prevalence of FQ-resistant pathogens (including ST131) and that earlier FQ therapy selects for them.
Molecular typing showed that more than 80% of the ST131 isolates represented the fimH30 subclone, of which half were pulsotype 968 or 800. Together, these predominant pulsotypes accounted for nearly half of the ST131 isolates that were FQ resistant or caused a healthcare-associated infection and over one-third of community-associated ST131 isolates. We speculate that, although sporadic emergence and expansion of new ST131 types is occurring in hospital and community settings alike, globally dominant pulsotypes 968 and 800 are expanding primarily within healthcare facilities and LTCFs, perhaps because of suboptimal infection control practices and extensive (and often inappropriate) antimicrobial use.
Limitations of this study include that it was from a single center and analyzed primarily isolates obtained from urine specimens. Thus, our results may not be generalizable to other locales or other clinical syndromes, such as E. coli bacteremia or meningitis. Additionally, because the study was retrospective, we likely were unable to accurately distinguish colonization from infection in all patients and may have misclassified some of the outcomes. Finally, the study’s observational nature precludes confident assessment of causality; all associations are simply that, with multiple possible explanations.
Despite these limitations, the study results have important clinical implications. We have identified significant risk factors for ST131 infection; this can assist with more timely and appropriate empirical treatment of patients with ST131 infection, which, in turn, has the potential both to minimize the spread of ST131 and to improve outcomes of ST131-associated infections. In addition, we have confirmed that, in the United States, as in Europe, healthcare settings and LTCFs likely are reservoirs and sites of ongoing transmission of ST131, including its globally predominant pulsotypes 968 and 800. Our results highlight the necessity of implementing enhanced antimicrobial stewardship and infection control interventions in these settings to reduce selection for and interrupt transmission of the highly successful antimicrobial-resistant ST131 clonal group.