Infections caused by extended-spectrum β-lactamases (ESBLs)-producing E. coli and K. pneumoniae have been described in the hospital setting,1 although during the last decade these organisms have begun to disseminate into the community, becoming an emerging public health problem.2 ESBLs are enzymes commonly associated with TEM and SHV. However, many E. coli and K. pneumoniae isolates possess the gene encoding ampC cephalosporinase.3 Moreover, CTX-M-type ESBLs have emerged within the community, particularly among E. coli and K. pneumoniae isolated from urinary tract infections (UTIs), with a widespread prevalence and multidrug resistance in many countries worldwide.2,4 Multidrug resistance expressed by CTX-M producing isolates from the community is often associated with the presence of multiple ESBLs genes, as well as aminoglycoside and quinolone resistance genes,5,6 thereby limiting the choice of effective antimicrobial drugs.7

The aim of this study was to describe the presence of the CTX-M-1 phylogenetic subgroup ESBL associated with TEM and SHV genes and the gene encoding cephalosporinase, CMY-2, in E. coli and K. pneumoniae isolates from community-acquired UTIs.

Community-acquired UTIs caused by ESBL-producing organisms are a cause of concern due to the clinical failure of empirical treatment protocols. This study shows two main pathogens causing UTIs in the community (E. coli and K. pneumoniae). The results show that expressed resistance to quinolones (ciprofloxacin) is similar among community isolates of E. coli and K. pneumoniae, 33% and 38%, respectively (Table 1). However, significant resistance was presented to trimethoprim-sulfamethoxazole (50%) and tetracycline (60%) in E. coli isolates, characterizing an alarming resistance to these two families of antibiotics.

ESBL production found among community isolates of E. coli was 11.7% and 19% for K. pneumoniae, rates similar to that found in hospital isolates;1,17K. pneumoniae is the main ESBL-producing organism worldwide.18 In Latin American countries, community-acquired ESBLs are starting to appear with rates up to 28.7% among E. coli and K. pneumoniae isolates,19 while in Europe reported rates are of only 1.5% to 5.6%, respectively.20 The presence of ESBL-producing urinary isolates in the community is a significant public health problem that unavoidably increases health care costs for patients and health care providers due to the use of carbapenems, since the oral agents (nitrofurantoin and fosfomycin), used for treatment of UTIs, are unsuitable due to the enormous resistance-development ability demonstrated by uropathogens, which has led to a loss of interest in these drugs. Therefore, carbapenems appear to be the drugs of choice for the treatment of UTIs caused by ESBL-producing E. coli and K. pneumoniae, considering their rational use.21,22

In Colombia, the prevalence of community-acquired ESBL-producing E. coli and K. pneumoniae is not well known; the findings of TEM and SHV enzymes in this study show the spread of these enzymes in hospital and community isolates in Colombia.23 However, the presence of community-acquired CTX-M-producing Enterobacteriaceae (seven E. coli and three K. pneumoniae), is of concern especially in E. coli, because these enzymes are commonly encoded by plasmids. Besides, there is the possibility that isolates found in this study are associated with well-characterized ST131 and ST405, which are multidrug-resistant intercontinental clones responsible for the dissemination of blaCTX-M-15, as previously reported in Colombia.24 Multidrug-resistance expressed by ESBL-producing Enterobacteriaceae in this study was presented to aminoglycosides, trimethoprim-sulfamethoxazole, tetracycline, and quinolones (Table 2).

ESBL-producing K. pneumoniae strains are more related to hospital outbreaks. However, the current distribution of ESBL carrying microorganisms in patients with community-acquired UTIs is a generalized problem, thus producing a flow of isolates from the community to the hospital setting.25 Likewise, the strains of E. coli and K. pneumoniae that harbored multiple ESBL genes are important, because it has been reported that isolates carrying multiple ESBL genes had a greater resistance to various classes of antibiotic mediated through acquisition of genes located on mobile genetic elements such as plasmids, transposons, or integrons.5,26 Furthermore, the fact that they harbor multiple ESBL genes in combination with the gene encoding cephalosporinase CMY-2 could explain the cefoxitin resistance (four E. coli and two K. pneumoniae), as reported in previous studies that have shown the blaCMY-2 gene linked downstream with the promoter sequence ISECP1,27 increasing the likelihood of therapeutic failures and difficulty for laboratory phenotypic detection of ESBL.28,29Finally, resistance expressed by E. coli and K. pneumoniae isolates, and molecular confirmation of ESBL genes were analyzed using statistical models to measure the crude association between a positive result for ESBL in isolates of E. coli and resistance to tobramycin (p≤0.001), tetracycline (p=0.025) and ciprofloxacin (p=0.01) (Table 3). In K. pneumoniae isolates, an association was found between a positive result for ESBL and resistance to tobramycin (p=0.002), ciprofloxacin (p=0.002), and trimethoprim-sulfamethoxazole (p=0.027) (Table 3). However, in multivariate analysis did not show non-β-lactam drugs as an independent variable. This finding suggests that non-β-lactams resistance remained independently associated with ESBL, but for reasons unrelated to ESBL genes. Studies have shown that non-β-lactam and β-lactam (ESBL) resistance encoding genes are located in plasmids.13,30 This common location may explain the resistance to previously mentioned antibiotics. Nevertheless, it is interesting that resistance to ciprofloxacin was associated with presence of ESBL and resistance to other antibiotic classes (Table 2). To some extent, this could be explained by its extensive use as an empirical drug for treatment of UTIs, resulting in strong selective antimicrobial pressure in the community. Similar data were found in previous studies.31–33

Detection of CTX-M ESBL in uropathogens isolated from the community is of concern because of the enormous potential for multidrug resistance of strains that produce these enzymes, especially if E. coli isolates from this study could be related to the intercontinental clones ST131 and ST405, because empirically administered therapies will fail, which could lead to complicated UTIs.

All authors declare to have no conflict of interest.