Daniel M. Keller, PhD

September 13, 2012

September 13, 2012 (San Francisco, California) — A recent finding that people in the Netherlands exhibit a high prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is something of a conundrum.

"We found a prevalence of 8.5%, which is very high. It's remarkable because the Netherlands is a country with low antibiotic use and the lowest resistance rates in clinical isolates in Europe," Elien Reuland, MD, from the VU University Medical Center in Amsterdam, the Netherlands, reported here at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy. She noted that among these bacteria, coresistance to ciprofloxacin, cotrimoxazole, and gentamicin is common.

Of the 9000 VU Medical Center patients invited to participate in the study by mail, 1713 (mean age, 52 years; range, 18 to 95 years) returned a brief questionnaire and a fecal sample in transport medium. Enterobacteriaceae were isolated and screened for the production of ESBLs, carbapenemases, and antibiotic-resistance genes. The researchers identified resistant species and tested them for antibiotic susceptibility.

Overall, 145 (8.5%) of the 1713 samples contained ESBL-producing Enterobacteriaceae, 132 (91%) of which were Escherichia coli. Of the 145 samples, 61% were resistant to cotrimoxazole, 31% to ciprofloxacin, 26% to gentamicin, and 11% to all 3. Only 1 (0.06%) of the 1713 samples was a carbapenemase-producing strain.

In contrast to E coli strains recently isolated from patients in hospitals and long-term care facilities in the Netherlands, where the most common ESBL gene is CTX-M-1, 63 (43%) of the 145 ESBL-producing Enterobacteriaceae community isolates contained the CTX-M-15 gene, 25 (17%) contained the CTX-M-1 gene, and 20 (14%) contained the CTX-M-14/18 gene.

The researchers conclude that there is a high prevalence of ESBL-producing Enterobacteriaceae carriage in the Netherlands, with a high proportion of coresistance to some common antibiotics. However, the distribution of resistance genes in ESBL-producing E coli community isolates differs from that seen in E coli strains in clinical isolates. Although only 1 of the 1713 specimens exhibited production of a carbapenemase, the researchers note that the finding "in the community is threatening."

Dr. Reuland offered some possible explanations for the study findings. "In the Netherlands, there's a very high use [of antibiotics] in food-producing animals, so maybe there is a relationship there. On the other hand, we found CTX-M-15 in 43%, which is what is found in the rest of Europe and the rest of the world," she said. "We have to analyze all the questionnaires [to determine] if there might be a relationship between previous antimicrobial use, a previous hospital stay, [travel], or risk factors with food or something."

She added that in light of the already high prevalence of ESBL-producing Enterobacteriaceae in the community, the value of contact isolation in hospitals needs to be looked at.

Jesús Rodríguez-Baño, MD, PhD, head of infectious diseases at the Hospital Universitario Virgen Macarena and professor at the University of Seville in Seville, Spain, told Medscape Medical News that he finds the very high prevalence of people in the community colonized with ESBL-producers interesting because the prevalence in infections is lower than in other countries.

"Probably a lot of patients are acquiring the ESBLs through food or person-to-person transmission inside the home. Since they use very low quantities of antibiotics in the Netherlands, these patients [do not acquire] ESBL-producing infections."

He noted that in Spain, there is a similar percentage of people colonized but a higher percentage of people infected with ESBL-producing organisms. "This is probably due to the fact that we use more antibiotics that select for these isolates when causing an infection."

Dr. Rodríguez-Baño explained that infection with resistant organisms is a multifactorial process. "One is the risk factor for acquiring the microorganism that is resistant. Another is the selection once you are colonized. Obviously, the use of antibiotics will favor the colonization of other people.... [Another process is] once colonized, developing an infection," he explained. "We are trying to understand the complex relation" between infection and antibiotic use, he said.

There was no commercial funding for the study. Dr. Reuland and Dr. Rodríguez-Baño have disclosed no relevant financial relationships.

52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract C2-104. Presented September 9, 2012.