Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae: Epidemiology, Risk Factors, and Duration of Carriage

University dissertation from Department of Clinical Sciences, Lund University

Abstract: In human medicine, the most important family of bacteria is Enterobacteriaceae, which includes genera and species that cause well-defined diseases and also nosocomial infections. These bacteria can give rise to numerous infections such as septicaemia and urinary tract infections. It is important to combat these infections with effective antibiotics, because many of them are associated with high mortality rates if left untreated. In infections with ESBL-producing bacteria in low-endemic countries, the initial empirical antibiotic treatment will probably be ineffective and thus lead to higher mortality if the infection is severe. Therefore, it is important to identify patients that are at risk of such infections and also to avoid spreading the bacteria.
The present research aimed to determine the cause of the rapid increase in ESBL-producing Enterobacteriaceae in patients in our hospital and our community. Our initial results clearly demonstrated that huge numbers of ESBL-positive faecal samples were collected from patients who contracted travellers’ diarrhoea after visiting high-risk areas. Twenty-four percent of patients with travellers’ diarrhoea were colonized with ESBL-producing. Strains of ESBL-producing E. coli were especially common in patients who visited Egypt (50%) and India (78.5%). Follow-up of the same cohort (Paper III) regarding duration of colonization with ESBL-producing E. coli showed that 10/41 patients were positive for such bacteria after 3–8 months, although four of the 10 carried a different strain than the one initially identified. After three years, 4/41 patients still harboured ESBL-producing E. coli, although one of those four carried two new strains. This immense impact of travelling on faecal carriage is noteworthy, especially considering that global travel is still increasing at the rate of almost a billion passengers annually.
The total prevalence of faecal carriage of ESBL-producing bacteria in the study population (Paper II) was 1.9% in 2008 and 5.0% in 2010. The prevalence increased from 1.8% to 6.8% among hospitalized participants and from 2.1% to 3.0% among patients in primary care. These observations distinctly demonstrate that ESBL-producing bacteria represent an emerging problem in the community, particularly in hospitals. The findings also concur with our results suggesting that hospitalization longer than one month, especially in a surgical ward, constitutes a risk for infection with ESBL-producing E. coli (Paper V). Despite lack of evidence of patient-to-patient transmission in our hospital, the described findings highlight the need for good infection control and, when indicated, narrow and rational antibiotic therapy to lower the selective pressure.
We are among the first to study possible occurrence of ESBL-producing Enterobacteriaceae in food in Sweden (Paper V). We found no such bacteria in either domestic or imported foods. However, significantly more Enterobacteriaceae were detected in lettuce than in air-dried/cured meat products.
The rapid increase and spread of the carbapenem-resistant NDM-1-producing Enterobacteriaceae, especially in India and the Middle East, plainly illustrates that the current antibiotic situation is very precarious, and that it is essential to continue development of new antibiotics. The most important factor in this context is probably the need for establishing well-functioning sewage systems in large parts of the world (primarily Asia and Africa). Ensuring that people in developing countries have access to fresh food and water without the risk of faecal contamination would solve many problems.

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