In Vitro Antimicrobial Resistance of Urinary Escherichia coli Isolates among U.S. Outpatients from 2000 to 2010

Abstract

This study examines in vitro antimicrobial resistance data from Escherichia coli isolates obtained from urine samples of U.S. outpatients between 2000 and 2010 using The Surveillance Network (TSN). Antimicrobial susceptibility results (n = 12,253,679) showed the greatest increases in E. coli resistance from 2000 to 2010 for ciprofloxacin (3% to 17.1%) and trimethoprim-sulfamethoxazole (TMP-SMX) (17.9% to 24.2%), whereas nitrofurantoin (0.8% to 1.6%) and ceftriaxone (0.2% to 2.3%) showed minimal change. From 2000 to 2010, the antimicrobial resistance of urinary E. coli isolates to ciprofloxacin and TMP-SMX among outpatients increased substantially.

TEXT

Antimicrobial resistance significantly increases patient morbidity, costs of treatment, rates of hospitalization, and use of broad-spectrum agents (7). Resistant Escherichia coli isolates are associated with decreases in clinical cure rates and higher risk of recurrence (17, 20).

Several studies have described the in vitro susceptibility of E. coli isolates among outpatients in the United States, and most of these studies have focused on women. The most-recent published data available for U.S. outpatients were collected from April 2003 to June 2004 and suggested the levels of antimicrobial resistance of urinary E. coli isolates to be 39.3% for ampicillin, 22.6% for trimethoprim-sulfamethoxazole (TMP-SMX), 6.8% for ciprofloxacin, and 1.4% for nitrofurantoin (22). Other, smaller regional studies suggested a continued trend of rising resistance in the outpatient setting (8, 13, 16).

Limited data are available to describe long-term trends in antimicrobial resistance of E. coli isolates among outpatients in the United States. The objective of this study was to examine trends of antimicrobial resistance of urinary E. coli isolates among outpatients in the United States from 2000 to 2010.

Antimicrobial susceptibility test results were obtained from The Surveillance Network (TSN) Database—USA (Eurofins Medinet, Chantilly, VA). This surveillance database collects data from over 200 institutions in the United States, and antimicrobial susceptibility testing is performed on-site by each laboratory in accordance with FDA-approved testing methods and interpreted using Clinical and Laboratory Standards Institute (CLSI)-recommended breakpoints. TSN data have been used before to evaluate trends in antimicrobial resistance, and further details of quality control have been described previously (5, 9, 18, 19).

The present study included antimicrobial susceptibility data for urinary E. coli isolates obtained from U.S. outpatients between 2000 and 2010. Outpatients are defined as individuals who visited emergency departments, hospital-based outpatient clinics, and physicians' offices. E. coli isolates with intermediate susceptibility were not classified as being resistant. The outcomes of interest in this study were the changes in and most-recent prevalence of antimicrobial resistance to commonly prescribed oral agents used to treat urinary tract infections (UTIs). Cephalothin and ceftriaxone, both intravenously administered agents, were selected as narrow- and broad-spectrum cephalosporin surrogates, respectively, for their orally administered formulations.

A chi-square test was performed for each antimicrobial agent to determine whether a significant difference existed between resistance rates observed in 2000 and those observed in 2010. An alpha level of 0.05 was used. Analyses were performed using Statistical Analysis Software (SAS) version 9.1.

Antimicrobial susceptibility results (n = 12,253,679) for urinary E. coli isolates obtained from outpatients in the United States from 2000 to 2010 were examined (Table 1). The greatest increases in resistance among isolates obtained from all outpatients from 2000 to 2010 were observed for ciprofloxacin (from 3% in 2000 to 17.1% in 2010) and TMP-SMX (17.9% to 24.2%) (Fig. 1). Conversely, over the same time period, nitrofurantoin (0.8% to 1.6%), amoxicillin-clavulanate (5% to 5.3%), and ceftriaxone (0.2% to 2.3%) demonstrated only small changes in resistance. In 2010, ampicillin, tetracycline, cephalothin, and cefuroxime showed antimicrobial resistance rates of 43.4%, 24.9%, 18.1%, and 5.0%, respectively.

Table 1.

Annual rates of resistance of urinary Escherichia coli isolates to select antimicrobials among all outpatients from 2000 to 2010^a

Antimicrobial agent	No. of test results	Antimicrobial resistance rate (%) for indicated yr											Total change (%) from 2000–2010b
		2000	2001	2002	2003	2004	2005	2006	2007	2008	2009	2010
Ciprofloxacin	1,836,598	3	3.7	5	6.2	7.5	9.7	12.2	14.1	16	16.3	17.1	14.1
TMP-SMX	2,034,254	17.9	17.8	18.1	18.2	19.4	20.2	20.8	21.9	22.9	23	24.2	6.3
Ampicillin	2,002,221	38.2	38.1	38.2	38.2	38.2	39.4	40.5	41.5	42.4	42.4	43.4	5.2
Cefuroxime	806,659	1.5	1.9	2.1	2.3	2.4	2.3	2.9	3.2	3.7	4	5	4.5
Cephalothin	502,231	14	15.8	14.6	15	14.5	15.7	16.9	16.6	16.4	16	18.1	4.1
Tetracycline	580,328	22.6	22.1	22.1	21.1	21.9	22	23.5	23.7	24.4	24.5	24.9	2.3
Ceftriaxone	1,759,006	0.2	0.2	0.3	0.3	0.5	0.6	0.9	1.2	1.6	1.9	2.3	2.1
Nitrofurantoin	1,972,633	0.8	1	1.1	1.1	1	1.1	1.4	1.5	1.5	1.6	1.6	0.8
Amox-Clav	759,749	5	4.1	5.3	4.5	3.7	3.8	5.6	8.2	9.9	6.6	5.3	0.3

^aIsolates demonstrating intermediate susceptibility were not counted as resistant. Amox-Clav, amoxicillin-clavulanate; TMP-SMX, trimethoprim-sulfamethoxazole.

^bAll antimicrobial agents demonstrated statistically significant changes from 2000 to 2010.

Fig 1.

Cumulative annual change in E. coli antimicrobial resistance in outpatient urinary E. coli isolates from 2001 to 2010. Amox/Clav, amoxicillin-clavulanate.

Emerging antimicrobial resistance of E. coli in the outpatient setting is well documented (2, 3, 7, 12, 14). In the early 2000s, quinolones surpassed sulfa drugs as the most common class of antimicrobials prescribed by clinicians to treat uncomplicated UTIs (10). This increase in provider use of fluoroquinolones may account for the rapid rise in antimicrobial resistance of E. coli to ciprofloxacin, as resistance to this agent has been shown to correlate with the level of use (8, 15, 21). Due to the propensity of E. coli to acquire resistance to this agent, use of ciprofloxacin for empirical treatment of UTIs in outpatients should be used sparingly and only where local antimicrobial resistance rates remain low (4).

Antimicrobial resistance of urinary E. coli isolates to TMP-SMX continued to increase from 2000 to 2010, a trend that has continued for decades (1, 6, 11). In the 2010 IDSA guidelines for treating acute uncomplicated cystitis in women, TMP-SMX is recommended as the second-line antimicrobial agent (4). Our data are consistent with previous reports regarding increases in antimicrobial resistance of urinary E. coli isolates to TMP-SMX and potential subsequent decreases in its efficacy as empirical therapy among U.S. outpatients.

Levels of antimicrobial resistance of E. coli to cephalothin, the narrow-spectrum oral cephalosporin surrogate, were higher than those for expanded-spectrum (cefuroxime) and broad-spectrum (ceftriaxone) cephalosporins. It is important to note that while the absolute change in antimicrobial resistance to ceftriaxone was small (0.2% in 2000 to 2.3% in 2010), there was a 10-fold increase in resistance of E. coli to this agent over the study time period. Though these changes do not bear immediate clinical significance, future surveillance of antimicrobial resistance to this agent is warranted.

The in vitro antimicrobial resistance rates among E. coli isolates in our investigation were consistent with those reported previously (6, 11, 22). For example, antimicrobial resistance of E. coli to nitrofurantoin demonstrated little change over our study time period, a finding that is consistent with the resistance prevalence reported in the NAUTICA study (22).

It is important to note the strengths and limitations of our data. The strengths of our study include the large number of isolates, the variety of antimicrobial agents studied, the large number of reporting institutions within the United States, the long time period for which data were reported, and the geographically representative distribution of isolates from TSN. The limitations of our study include a lack of central laboratory testing, the use of multiple susceptibility test methods, and an assumed underrepresentation of isolates from those for whom empirical treatment was successful. These data should be interpreted with caution. Although traditional in vitro surveillance systems are well designed to provide insight into overall trends and prevalence of antimicrobial resistance, they are not meant to guide antimicrobial therapy in the management of individual clinical cases.

In summary, our study shows that from 2000 to 2010, antimicrobial resistance of urinary E. coli isolates to ciprofloxacin and TMP-SMX increased substantially but that resistance to nitrofurantoin and ceftriaxone remained low. Given the frequency with which UTIs are treated empirically, compounded with the speed that E. coli acquires resistance, prudent use of antimicrobial agents remains crucial.