Clinical Microbiology and Infection. 2013 Feb;19(2):E87-90.

Shift in CTX-M genotypes has determined the increased prevalence of extended-spectrum β-lactamase-producing Escherichia coli in south-western Sweden.

Lisa Helldal 1, Nahid Karami 1, Kerstin Florén 1, Christina Welinder-Olsson 1, Edward R.B. Moore 1,2 and  Christina Åhrén 1,3

1 Department of Infectious Diseases, 2 Culture Collection University of Gothenburg (CCUG), Department of Infectious Diseases, 3 Infection Control, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy of the University of Gothenburg, Guldhedsgatan 10A, 41346 Göteborg Sweden

 

ABSTRACT

The prevalence of Escherichia coli producing extended-spectrum β-lactamases (ESBLs) markedly increased during 2004–2008 in south-western Sweden, with a greater increase in urinary isolates in hospitals (0.2–2.5%) than in the community (0.2–1.6%). ESBLs of genotype CTX-M predominated, with a significant (p <0.02) shift from the CTX-M-9 to CTX-M-1 phylo-group occurring among urinary ESBL-producing E. coli isolated early (n = 41) as compared with late (n = 221) in the study period. The increase in ESBL-producing E. coli was polyclonal and only partly attributable to an increase (0–24%) in the number of O25b-ST131 isolates carrying CTX-M-15. The increase was prominent in men and in elderly patients, and warrants continued surveillance.

PMID: 23190133

 

SUPPLEMENT

The emerging pandemic of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) poses a serious threat to the successful treatment of common bacterial infections. During the past decade, the CTX-M β-lactamases, mainly associated with Escherichia coli, have emerged as the predominant ESBL type worldwide [1]. CTX-M-15 and CTXM-14, belonging to the CTX-M-1 and CTX-M-9 phylo-groups, respectively, are currently the most widely-distributed CTX-M genotypes [2] and are increasingly associated with community-acquired infections [1]. E. coli serotype O25b:H4 and sequence type (ST) 131, by multi-locus sequence typing, carrying CTX-M-15 has been reported worldwide [3,4]. The frequency of ESBL-producing bacteria has been reported to be increasing also in the Scandinavian countries [5]. We described the epidemiology of ESBL-producing E. coli, isolated from patients in a municipal area in south-western Sweden as the incidence of ESBLs began to increase. Antibiotic susceptibilities of isolates were confirmed according to the Swedish Reference Group for Antibiotics (http://www.nordicast.org). The prevalence of ESBL-producing E. coli increased from 0.2% (23/11,337) to 1.9% (224/11,953) among urine isolates during 2004–2008. The increase was greater in the hospitals (to 2.3%; 82/3,284) than in the community (to 1.6%; 142/8,669) (Figure 1). The corresponding numbers in blood samples were 0–3% (13/434). Other Enterobacteriaceae– producing ESBLs were rare. Non-repetitive ESBL-producing E. coli isolated from urine samples during two periods (September 2003 to April 2005 and April 2008 to March 2009) were investigated further. The distribution of ESBL-producing E. coli reflected the distribution of urinary tract infections in the general population. An increase in isolates carrying CTX-M was seen in the elderly, constituting almost 50% of the isolates in the later period. Overall, an increase in the number of E. coli harbouring TEM and/or SHV or OXA, in addition to the CTX-M-enzymes, was recorded (Table 1). However, the CTX-M-1 group in combination with both TEM and OXA, remained comparatively low (20% vs 21%) and CTX-M-1 with OXA decreased (55% vs 35%) between the study periods. In the earlier study period, only four ESBL-E. coli O25b-ST131 isolates were detected. The number of ESBL-E. coli O25b-ST131 isolates from urine samples increased significantly (p<0.05), constituting 26% in the community and 21 % in the hospital settings in the latter period, although less than 0.5% of all E. coli urine isolates, irrespective of setting. All O25b-ST131 isolates from the earlier period carried CTX-M-15. Later, these isolates were shown also to carry CTX-M-9 and CTX-M-2 groups, as well as non-CTX-M beta-lactamases (Table 1). In the latter time-period, the combination of OXA with CTX-M-1 was significantly (p<0.001) more prevalent (39/47) in E. coli O25b-ST131 than among other E. coli with CTX-M-1 group (53/119) (Table 1), as was non-susceptibility to ciprofloxacin, trimethoprim, and tobramycin (p<0.05, 28/47 versus 49/119. The combination of CTX-M-1, TEM, OXA and tobramycin resistance was seen in 11% of ESBL-E. coli in the late period of which 28% were O25b-ST131 isolates.

The epidemiology of ESBL-producing Enterobacteriaceae has been reported from many countries in which mostly microbiological aspects have been covered. In this study, the molecular epidemiology is described, with respect to patient data, in a large, well-defined region with a single, centralized laboratory system, over a 5-year period, starting from the point of time when these bacteria began to emerge in south-western Sweden. This is one of the first reports covering the epidemiology of O25b-ST131 ESBL-E. coli isolates over an extended period in Sweden. Furthermore, this study sheds light on how ESBL-producing bacteria may be introduced into a society like Sweden, with low antibiotic pressure, low levels of antibiotic resistance in general and, for the past decades, also low levels of other multi-resistant bacteria, including within the hospital environment. The epidemiology described in this study demonstrates that south-western Sweden was affected by the global ESBL pandemic later than other areas, but that these bacteria now are well established in the region. In contrast to previous epidemics of multi-resistant bacteria, Sweden this time faces an epidemic similar to other countries, probably due to the establishment of these bacteria in the community. This warrants continuous surveillance of the ongoing ESBL pandemic also at the local level, as performed in this study.fig1Figure 1. Total number (bars) of ESBL-E.coli and frequency (lines) of ESBL-E.coli of all E. coli isolated from patients with urinary tract infections in community and hospital settings, from 2004-2008 in south-western Sweden.

 

Table1. Distribution of ESBL genes, the O25b-ST131 genotype and the numbers of PFGE- and MLST-types detected in urinary E. coli during the two study-periods

tab1

a No of PFGE-types/isolates tested, adding up to >80 PFGE-types for the entire study period. These were distributed within at least 30 sequence types by MLST.

ST131, ST648, ST38, ST12, ST167, ST617, ST405 and ST69 were found in 3 or more isolates, listed in order of prevalence.

b The proportion of CTX-M-1 phylogroup isolates among those with a CTX-M increased significantly (p<0.002) between the two study periods

c All were CTX-M-15 i.e., the genes of all 025b-ST131 isolates, 4 of 16 non-025b-ST131 isolates tested from the early period and 11 of 119 tested from the late period.

One additional isolate from the last group harboured CTX-M-1.

dThe proportion of CTX-M-9 phylogroup isolates among those with a CTX-M decreased significantly (p<0.02) between the two study periods

e One isolate with CTX-M-9, three with CTX-M-14a. Genes from five isolates were sequenced

f One isolate with CTX-M-27 the remaining CTX-M-14. Genes from eleven isolates were sequenced.

g Three isolates with CTX-M-27 and two with CTX-M-14.

 

REFERENCES

1.  Cantón R, Coque TM. The CTX-M β-lactamase pandemic. Current Opinion in Microbiology. 2006;9(5):466-75.

2.  Pitout JD, Laupland KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. The Lancet Infectious Diseases. 2008;8(3):159-66.

3.  Peirano G, Pitout JDD. Molecular epidemiology of Escherichia coli producing CTX-M β-lactamases: the worldwide emergence of clone ST131 O25:H4. International Journal of Antimicrobial Agents. 2010;35(4):316-21.

4.  Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, et al. CTX-M: Changing the face of ESBLs in Europe. Journal of Antimicrobial Chemotherapy. 2007;59(2):165-74.

5.  EARS-Net. Available from:  http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/

 

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