Emergence of Extended-Spectrum β-Lactamase-Producing Escherichiacoli in Community Hospitals throughout North Carolina: A Harbinger of a Wider Problem in the United States?

Strains of extended spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) have become endemic in community settings in numerous countries during the past 5 years [1-5]. In affected countries, the incidence of community-onset urinary tract infection due to ESBL-EC has dramatically increased. Frequently, patients with these infections require hospital admission, because many strains of ESBL-EC are resistant to nearly all available oral antibiotics [6]. Of note, this trend has not been described in the United States. Instead, acquisition of ESBL-producing organisms in American patients has been considered to be predominately nosocomial, and Klebsiella pneumoniae has been considered to be the most common ESBL-producing species recovered in American hospitals [7, 8]. In the present study, we sought to determine whether the incidence of infection due to ESBL-EC has been increasing in North Carolina with use of data obtained from community hospitals.

Methods. We calculated incidence rates of isolation of ESBL-EC with use of data collected prospectively from community hospitals in North Carolina. Second, we compared the characteristics of patients infected with ESBL-EC with those of patients infected with ESBL-producing Klebsiella pneumoniae (ESBL-KP) to evaluate the epidemiology of infection caused by ESBL-EC.

The Duke Infection Control Outreach Network (DICON) provides infection surveillance services to community hospitals. For DICON-affiliated hospitals, data collected on patients with ESBL-producing isolates are routinely entered into a centralized database. These data include year of birth, sex, ethnicity, date of hospital admission, previous admissions to the same hospital during the preceding year, specimen collection date and type, diabetes status, dialysis dependence, and whether admission is from home or another health care facility. Each hospital also records patient-days.

For the present study, we included data from 16 DICON-affiliated community hospitals in North Carolina. Three community hospitals that joined DICON after January 2005 were excluded. The 16 study hospitals had a mean of 222 beds (range, 102-403 beds) and were located in 16 different counties throughout the state. All patients with ESBL-producing organisms isolated from 1 January 2005 through 30 June 2008 (study period) were included. ESBL status was determined either by methods of the Clinical Laboratory Standards Institute or by automated platforms (Vitek II [bioMérieux] or Microscan Walkaway [Dade Behring]) using panels provided by the manufacturer for this purpose.

Specimen types were recorded for all patients. All calculations were performed using the first isolate for each patient. Hospital-onset infection was indicated by positive results of culture of specimens collected >2 days after hospital admission, and community-onset infection was indicated by positive results of culture of specimens collected ⩽2 days after hospital admission. Community-onset infections were further classified as either health care associated or community associated [9]. Patients with health care-associated infection had ⩾1 of the following characteristics: home health care, admission from a nursing home or long-term care facility, transfer from another hospital, dependence on dialysis, or admission to a hospital within the previous 12 months. All other community-onset infections were defined as community-associated infections.

Patients with missing data were excluded from analyses requiring those data. Proportions were compared using the χ²test, as appropriate. Poisson regression was used to analyze changes in rates (SAS software, version 9.1; SAS Institute).

Results. The aggregate rate of isolation of ESBL-EC at the 16 study hospitals increased from 0 to 12 patients per 100,000 patient-days during the study period (P<.001 ) (figure 1). The first patient with an isolate of ESBL-EC was identified in December 2006. Thereafter, numerous patients were identified at 13 study hospitals. In 2008, ESBL-EC isolation rates among individual hospitals ranged from 5.7 to 36.4 patients per 100,000 patient-days. Before the study period, no patients with ESBL-EC isolates were identified in any DICON-affiliated hospital in North Carolina despite >1 million patient-days of surveillance since 2003. All isolates were recovered from specimens submitted for clinical purposes. Most isolates of ESBL-EC were recovered either from urine (80.2%) or from blood (8.6%). The remaining isolates were recovered from miscellaneous sites, including sputum, wound swabs, and surgical aspirates. No changes in the laboratory methods to detect ESBL-EC or changes in data collection methods were made during the study period.

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Figure 1

Aggregated rates of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae infection among 16 community hospitals in North Carolina (P values for trend were determined by Poisson regression).

In contrast to the trend observed for ESBL-EC, the aggregate rate of ESBL-KP isolation did not increase during the study period (figure 1). Rates of ESBL-KP isolation decreased or remained constant in 12 hospitals and increased in 4. Overall, 81 patients had isolates of ESBL-EC identified and 246 patients had ESBL-KP isolates identified during the study period. Most isolates of ESBL-KP were from urine (72.8%), sputum (9.3%), or blood (6.1%). The remaining isolates were recovered from miscellaneous clinical specimens.

The proportion of community-onset infection was significantly higher among patients with ESBL-EC infection than among patients with ESBL-KP infection (67 [82.7%] of 81 infections vs. 175 [71.1%] of 246 infections; P=.042 ). Similarly, there was an overall difference between the types of infection caused by the 2 organisms (i.e., hospital onset vs. health care associated vs. community associated; P=.029, by 3 by 2 χ²test). Although the proportions of health care-associated infection were similar between the 2 groups (45 [55.6%] of 81 ESBL-EC infections vs. 124 [51.0%] of 243 ESBL-KP infections), the proportion of community-associated infection was higher in the group with ESBL-EC infection than in the group with ESBL-KP infection; however, the difference did not reach statistical significance (22 [27.2%] of 81 vs. 48 [19.8%] of 243; P=.164 ).

There was no statistically significant difference in mean age between the 2 groups overall. However, after stratification by type of infection, effect measure modification existed between age and type of infection. In the subgroup with health care-associated infection, there were equal proportions of patients aged ⩽40 years in the group with ESBL-EC infection and the group with ESBL-KP infection (2 [4.4%] of 45 patients vs. 5 [4.0%] of 124 patients; P>.99 ); in the subgroup with community-associated infection, patients with ESBL-EC infection were more likely to be ⩽40 years of age (4 [18.2%] of 22 vs. 1 [2.1%] of 48; P=.031 ).

Overall, there was a statistically significant difference between the 2 groups with regard to from where patients were admitted (i.e., home vs. home health care vs. another hospital vs. nursing home; P=.02, by 4 by 2 χ²test). More specifically, although approximately half of the patients in each group were nursing home residents (51.9% in the ESBL-EC group vs. 50.0% in the ESBL-KP group), a higher proportion of patients with ESBL-EC infection than patients with ESBL-KP infection were admitted from home (37 [45.7%] of 81 vs. 90 [37.2%] of 242; P=.190 ). Conversely, higher proportions of patients with ESBL-KP infection than patients with ESBL-EC were either transferred from another hospital (11 [4.5%] of 242 vs. 0 [0%] of 81; P=.072 ) or were recipients of home health care (20 [8.3%] of 242 vs. 2 [2.5%] of 81; P=.078 ). Diabetes was also more common among patients with ESBL-KP infection than among patients with ESBL-EC infection (99 [41.1%] of 241 vs. 23 [28.8%] of 80; P=.062 ). No statistically significant differences in sex or ethnicity were observed.

Discussion. Our data show that rates of infection with ESBL-EC have increased in many community hospitals throughout North Carolina since 2006. The reason for the near simultaneous emergence of ESBL-EC in numerous, geographically separated community hospitals is uncertain. However, the temporal clustering of these infections and the high proportion of community-onset infections (83%) raise the possibility that the rate of acquisition of ESBL-EC has been increasing in the community in North Carolina. If this is indeed the case, it is likely that the burden of disease due to ESBL-EC in North Carolina is larger than our data suggest, because many patients with ESBL-EC infection may have been treated in the community without hospital admission. Potential sources of ESBL-EC in the community include colonized humans, as well as products of the food chain [10, 11]. Nursing homes are also likely to play a role in the spread of ESBL-EC, because approximately half of the patients with ESBL-EC infection who we identified were nursing home residents.

Spread of ESBL-EC in the community and in nursing homes has been previously described in countries such as Canada, the United Kingdom, Spain, France, and Israel [1-5]. This phenomenon has been associated with the CTX-M class of ESBL [1-5]. Interestingly, this class of ESBL has been considered to be uncommon in the United States [12]. Recently, however, researchers from a hospital in Texas reported that CTX-M was the most common class of ESBL found among isolates recovered by their laboratory [13]. In that study, the majority of CTX-M-producing isolates were E. coli, and the frequency of such isolates of E. coli increased over time. In fact, ESBL-EC became more frequently isolated than ESBL-KP after 2004. Thus, we believe that it is likely that the increase in the number of ESBL-EC infections that we observed was caused by a strain or strains of CTX-M-producing E. coli.

In contrast to the incidence of ESBL-EC infection, the incidence of infection due to ESBL-KP was unchanged during the study period. This suggests that different risk factors predispose patients to infection with these 2 ESBL-producing species. Supporting this hypothesis, ESBL-EC was more likely to cause community-onset and community-associated infections among patients aged <40 years than was ESBL-KP. These epidemiological differences may reflect differences between the individuals exposed to each of these organisms and/or intrinsic differences in the potential of these organisms to cause infection in otherwise healthy patients.

Regardless of the underlying explanation for our observations, the rapid and widespread increase in the incidence of community-onset infections due to ESBL-EC in North Carolina may have important clinical and epidemiological implications. For example, if the incidence of these infections continues to increase, ESBL-EC may become established as an endemic community-acquired pathogen in North Carolina, as it has in many other parts of the world. If this occurs, the choice of empirical antibiotics used to treat community-onset urinary tract infections may need to be modified. Furthermore, the increase that we observed may not be unique to North Carolina. Similar but as yet unrecognized increases in the incidence of community-onset infection due to ESBL-EC may also be occurring elsewhere in the United States.

We believe that follow-up studies are needed to evaluate the molecular epidemiology of ESBL-EC in North Carolina and to elucidate risk factors for infection. We also believe that additional studies using aggregated data collected from multiple community hospitals may be useful in other geographic areas of the United States. Such studies may allow for early detection of trends similar to those that we have reported.

• Received February 6, 2009.
• Accepted March 18, 2009.

• © 2009 by the Infectious Diseases Society of America