Antimicrobial Susceptibility Studies
Changing prevalence of Escherichia coli with CTX-M–type extended-spectrum β-lactamases in outpatient urinary E. coli between 2003 and 2008

https://doi.org/10.1016/j.diagmicrobio.2009.12.011Get rights and content

Abstract

One hundred ninety-three single-patient isolates of Escherichia coli harboring extended-spectrum β-lactamases (ESBL) were identified among 11 407 E. coli urine isolates recovered from single-patient outpatient urine cultures from 2003 to 2008. The percentage of ESBL-producing E. coli among community-onset E. coli urine isolates increased from 0.21% in 2003 to 2.99% in 2008. One hundred seven of the ESBL producers were positive for the presence of blaCTX-M genes. The percentage of CTX-M–producing E. coli rose from 0.07% in 2003 to 1.66% in 2008. The annual percentage of ESBL E. coli producing CTX-Ms changed from 35% in 2003 to 64% in 2008. Genes belonging to 3 blaCTX-M groups: blaCTX-M-1 group, blaCTX-M-2 group, and blaCTX-M-9 group, were detected. In addition, resistance to commonly used antimicrobial agents for community-acquired urinary tract infections was found common among CTX-M–producing E. coli isolates. Ertapenem and nitrofurantoin showed good in vitro activity against CTX-M producers.

Introduction

Extended-spectrum β-lactamase (ESBL)-producing isolates are commonly resistant to the multiple antibiotics used for treating infections caused by Gram-negative bacteria (Paterson and Bonomo, 2005). Most ESBLs can be divided into 3 groups: TEM, SHV, and CTX types based on the amino acid sequence homology (Pitout and Laupland, 2008). Variants of SHV and TEM ESBLs are most commonly associated with nosocomial pathogens, such as Klebsiella spp, and are often recovered from respiratory tract, intra-abdominal, and bloodstream infections (Paterson, 2006). Different from the TEM and SHV types of ESBLs, CTX-M enzymes are most often carried by Escherichia coli associated with community-onset urinary tract infections (UTIs) (Pitout et al., 2005). The CTX-M enzymes originated from the Kluyvera spp. of environmental bacteria and are associated with mobile elements (Olson et al., 2005, Rodriguez et al., 2004). Mobile genetic elements directly linked to blaCTX-M genes include the ISEcp-1–like insertion sequences, the CR1 (common region 1) element, phage-related sequences, and a putative transposase (Canton and Coque, 2006). The mobile elements not only are responsible for the dissemination of blaCTX-M genes but also may contribute to the high-level expression of the genes by providing additional promoters (Saladin et al., 2002). Transposons and plasmid-mediated transmission of blaCTX-M genes among genetic distinct strains have been shown in many different regions (Canton and Coque, 2006). Based on the observations that E. coli isolates with CTX-M are not clonal and blaCTX-M genes are carried on different genetic elements, spreading of CTX-Ms has been attributed to transmission of blaCTX-M genes through mobile genetic elements rather than dissemination of particular clones (Lewis et al., 2007, Livermore et al., 2007).

The CTX-M β-lactamase family consists of more than 50 members and is divided into 5 groups, including CTX-M-1 group, CTX-M-2 group, CTX-M-8 group, CTX-M-9 group, and CTX-M-25 group, with members of each group sharing >94% identity, whereas members from different groups share <90% similarity (Pitout and Laupland, 2008). Most CTX-M enzymes have greater activity against cefotaxime than ceftazidime and are inhibited by β-lactamase inhibitors (Walther-Rasmussen and Hoiby, 2004). Coresistance to other classes of antimicrobial agents are common among CTX-M–producing strains (Pitout et al., 2007, Pournaras et al., 2004, Woodford et al., 2004). Like TEM and SHV types of ESBLs, which are commonly resistant to aminoglycosides, tetracycline, and sulfonamides, a large numbers of CTX-M producers also show resistance to the fluoroquinolones.

CTX-M–type ESBLs are rapidly disseminating because they are detected in every populated continent and are responsible for major outbreaks in Europe (Canton and Coque, 2006). In the United States, the emergence of CTX-M–type ESBLs was first reported in 2003 (Moland et al., 2003). CTX-Ms were detected in isolates of several Enterobacteriaceae species in the United States, including E. coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Morganella morganii, Proteus mirabilis, and Proteus vulgaris (Castanheira et al., 2008, Lewis et al., 2007). Following Lewis's study, 2 other reports from the United States revealed high prevalence of CTX-Ms among the ESBL-positive isolates recovered in medical centers and the appearance of CTX-Ms in the E. coli isolates from the community (Castanheira et al., 2008, Hanson et al., 2008). However, the prevalence of CTX-M producers among community-onset E. coli causing UTIs in the United States has not been studied.

This study aims to evaluate the prevalence of CTX-M–type ESBLs among the E. coli isolates from patients with suspected community-onset UTIs from 2003 to 2008 and to assess the susceptibility of these isolates to common antibiotics important for treating community-acquired UTIs.

Section snippets

Isolate identification and collection

Isolates of E. coli used for the study were selected from the frozen isolates maintained by the clinical microbiology laboratory at Northwestern Memorial Hospital (NMH) in Chicago, IL. All isolates were recovered from voided urines from patients with suspected UTIs seen in outpatient clinics and the emergency room (ER) between January 2003 and December 2008. The colony count of each E. coli isolate in the original specimen was ≥105 CFU/mL. Isolates tested positive for ESBLs by Clinical and

Results

From January 2003 through December 2008, E. coli at colony counts of ≥100 000 CFU was recovered from 11 407 outpatient urine cultures. One hundred ninety-three isolates were identified as ESBL producers by double-disk synergy test. One hundred seven isolates tested positive for the presence of blaCTX-M genes (Table 2). Annual percentages of ESBL-producing E. coli among community-onset isolates increased by 14 times during the study period, from 0.21% in 2003 to 2.99% in 2008 (P < 0.001) (Table 2

Discussion

Although a high prevalence of community-acquired ESBLS, especially CTX-M–type ESBLs, has been reported in Europe and Asia for over 10 years, emergence of CTX-M–type ESBLs in the United States was only detected recently (Castanheira et al., 2008, Hanson et al., 2008, Lewis et al., 2007, Moland et al., 2003). In the United States, the prevalence of CTX-M–producing E. coli in the community is unknown. In this study, we show that nearly 3% of E. coli isolates recovered by outpatient urine cultures

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