Abstract
ESBL-producing bacteria became an increasingly hot issue over the last 15 years. Especially the rates in which Enterobacteriaceae were able to produce this extended-spectrum β-lactamase was the cause for real concern. Once bacteria start producing these enzymes, they become resistant to most antibiotics including the different classes of cephalosporins. For the treatment of patients suffering from an infection caused by ESBL-producing bacteria, only a few options remain. Antibiotics of the class of the carbapenems will do the job, but they are considered ‘last resort drugs’ that doctors rather do not use. Meanwhile, ESBL-producing bacteria are turning up everywhere: in hospitals, in long-time care facilities, in the general population, in food, in animals, in the soil, in the water, everywhere. And while the common gut-bacteria Escherichia coli and Klebsiella pneumoniae are often ESBL-producing in low- and middle-income countries, travel poses a risk for the global spread of these bacteria. Since human and veterinary health are closely linked, only the one health approach seems to be able to counter the ESBL problem.
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Notes
- 1.
Like penicillins, cephalosporins belong to the class of beta-lactam antibiotics. Cephalosporins are bactericidal medicines, i.e. they kill bacteria. They are used to treat pyelonephritis, infections of the respiratory tract and skin infections. Over the course of the years, four generations of cephalosporins have been launched on the market. Cephalosporins are reserve medicines, which are only used in hospitals when the bacteria are resistant to other drugs. They are usually administered via an infusion.
- 2.
The term ‘extended spectrum beta-lactamases’ (ESBLs) is used to describe a group of enzymes that make penicillins and cephalosporins ineffective (the antibiotics most frequently used to treat enterobacterial infections).
- 3.
A plasmid is a circular strand of DNA that is mobile, which therefore enables it to transfer genetic material between bacteria of the same or different species. Besides ESBLs, other resistance genes are often found on these plasmids as well.
- 4.
Escherichia coli or E. coli, named after the German microbiologist Theodor Escherich, is a Gram-negative bacterium of the enterobacteriaceae family. E. coli exists in several different forms. For example, EHEC is an E. coli. EHEC is described in detail in Chap. 9.
- 5.
An isolate is a bacteria culture that derives from a single bacterium.
- 6.
The term ‘morbidity’ describes the number of clinical cases, in this case caused by a bacterium.
- 7.
The term ‘mortality’ describes the death rate, in this case caused by an infection triggered by a bacterium.
- 8.
The Amphia Hospital in Breda, the Lievensberg Hospital in Bergen op Zoom, the Franciscus Hospital in Roosendaal and the St. Elisabeth and TweeSteden hospitals, both in Tilburg.
- 9.
Professor Roel Coutinho was at the time director of the Centre for Infectious Disease Control of the RIVM.
- 10.
The term ‘prevalence’ refers to a figure used in the study of health and disease (epidemiology), and indicates how many people in a specific group (population) have contracted a particular disease.
- 11.
The CTX-M gene is one of the genes that encodes bacteria fpr production of ESBLs.
- 12.
The term ‘cross-contamination’ is used when more than one patient is infected with an identical bacterium within the same period and at the same location.
- 13.
George Clemenceau, French doctor, politician, journalist and publicist. He was Prime Minister in the second half of the First World War and Minister of War (1917–1920).
- 14.
Every year worldwide around half a million children under five die from a pneumococcal infection. Thanks to sponsored vaccination programmes, a considerable reduction of pneumococcal infection deaths has been achieved in recent years (CDC 2018). Each year, about 10,000 people of all ages are admitted to hospital in the Netherlands with a pneumococcal disease of whom 6000 are aged 60 years and older. Of these people 900 die (RIVM 2020). In 2015, the member states of the EU reported more than 21,000 cases of confirmed invasive pneumococcal infections (ECDC 2019). In 2018, that number increased to nearly 25,000 (ECDC 2020c).
- 15.
Jean Carlet is president of the World Alliance against Antibiotic Resistance (WAAR), founded in June 2012.
- 16.
In 2002, less than 1% of all invasive E. coli and Klebsiella pneumoniae isolates in France produced ESBL. In 2010, the figures were 7.2% for E. coli and 17.8% for K. pneumoniae, and in 2015 they increased further, reaching 11% for E. coli and 30.5% for K. pneumoniae. In 2018, 30.8% of all invasive isolates of K. pneumoniae produced an ESBL and were resistant to third-generation cephalosporins. For E. coli, this figure was 9.6% (Pontiès et al. 2018, updated in 2019).
- 17.
From 2004 to 2009, there were between one and three episodes of enterobacteriaceae such as E. coli and Klebsiella spp. with carbapenemases in France every year. During each episode a number of linked cases of colonised or infected people occurred. From 2009 onwards the number of yearly episodes of CPE (Carbapenemase-Producing Enterobacteriaceae) were 10 episodes in 2009, 28 in 2010, 113 in 2011, 233 in 2012, 405 in 2013, 650 in 2014, 938 in 2015 and 1223 episodes in 2016. The cumulative number of cases in all episodes since 2004 was 5514. Almost half of all the episodes were imported from foreign countries, mostly from Northern Africa, by an index patient who was hospitalised there and then repatriated to a French hospital. Since 2009, the proportion of established import cases (an existing link to a foreign country is not always reported) has decreased from 71% in 2010 to 42% in 2015, suggesting an increase in proliferation of CPE in French hospitals. Of the 2385 episodes of CPE reported in France up to 1 January 2016, more than half (58%) were caused by Klebsiella pneumoniae and more than a third (38%) by E. coli. The role of E. coli has been increasing over the past few years, from 24% in 2012 to 42% in 2015. OXA-48 (-like) is by far the most frequent carbapenemase encountered. It is responsible for 78% of all cases in France (Pontiès et al. 2018, updated in 2019).
- 18.
See Chap. 4, Major outbreak at the Maasstad Hospital.
- 19.
The name of the doctor in question has been suppressed.
- 20.
For a definition of 4MRGN and 3 MRGN see Krinko (2013).
- 21.
The bacteria in question were a Klebsiella pneumoniae, a Citrobacter freundii and two Enterobacter cloacae.
- 22.
She is now working at the Bronovo Hospital in The Hague.
- 23.
In February 2014, work began on a major study of the incidence of Q fever in the population of Herpen. The preliminary findings were published at the end of May 2014, the final report in June 2015 (GGD Hart voor Brabant 2015). More than a third of the population of Herpen had fallen ill with Q fever at some time. A further 25% may possibly have been affected, although without further research this cannot be stated with certainty.
- 24.
These are confirmed cases. Roel Coutinho—at that time of the Q fever outbreak head of the Dutch Center of infectious diseases control—estimates that in reality about 50,000 people were infected with Q fever, and that moreover the number of deaths was two to three times greater than the official figures (RIVM 2018).
- 25.
‘Invasive’ in the sense that an instrument is introduced into the human body.
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van den Brink, R. (2021). The Beginning of the End. In: The End of an Antibiotic Era. Springer, Cham. https://doi.org/10.1007/978-3-030-70723-1_6
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