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The End in Sight?

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The End of an Antibiotic Era

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Abstract

The worldwide invasion of Enterobacteriaceae with a resistance to last-resort antibiotics of the class of carbapenems is speeding up. Medical tourism is one of the drivers, as well as globalisation of food trade and international travel habit. In South-East Asia—specifically the Indian subcontinent—the Mediterranean and the United States carbapenemase-producing enterobacteriaceae have become endemic or at least pretty common. Infections with this kind of bacteria are increasingly hard to treat, as shown by several examples of outbreaks that will be described below. One of the few remaining options to treat patients with an infection caused by a carbapenemase-producing microbe is colistin. But since this classic antibiotic is now frequently being used to combat infections with carbapenem-resistant bacteria, there is also an increase of colistin resistance. While halting the spread of carbapenemase-producing bacteria is of primordial importance, so is the development of new antibiotics to counter infections by these bugs.

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Notes

  1. 1.

    These were: a Klebsiella pneumoniae, an Escherichia coli and an Enterobacter cloacae.

  2. 2.

    In 2012, Jan Kluijtmans told me that he had heard from some colleagues in Asia that they were not allowed to publish anything about resistance problems any more. At the same time people were becoming more aware of the link between antibiotics use and resistance, for example in India and China.

  3. 3.

    In 2000 and 2001, Streptococcus pneumoniae was resistant to penicillin in 71% of cases, and in 92% of cases resistant to erythromycin (GARP 2010).

  4. 4.

    Forty-two per cent of Gram-negative Enterobacteriaceae were resistant to ceftazidime, 63% to gentamicin and 74% to nalidixic acid. Ceftazidime is a third-generation cephalosporin. Gentamicin is an aminoglycoside antibiotic and nalidixic acid is one of the (fluoro)quinolones (GARP 2010).

  5. 5.

    According to the GARP report on Vietnam, 25 types of antibiotics were withdrawn from the market in 2008 because of their poor quality. These included both medicines produced in Vietnam and imported ones. Antibiotics make up roughly a quarter of all illegal medicines taken off the market (GARP 2010).

  6. 6.

    Every worker or employee must contribute to the compulsory health insurance scheme. Insurance is free for pensioners and the poor. The insurance covers the costs of basic care, but also requires a patient contribution of around 20%. Since 2005, all medical treatment for children under six has been free.

  7. 7.

    Vietnam and India still use much fewer antibiotics per capita than the United States or southern European countries. Many Indian and Vietnamese people have very limited access to medical care, or none at all. They often buy antibiotics for a short period. That leads to underdosing, which considerably encourages the formation of resistance.

  8. 8.

    In the Netherlands, the consumption of antibiotics in the community was 9.5 DDD per 1000 inhabitants per day in 2019. The EU average was 19.4 DDD per 1000 inhabitants per day (ECDC 2020a).

  9. 9.

    CTX-M is the name of a group of plasmids that are closely related to one another. The latter are sections of DNA which are found loose in bacteria.

  10. 10.

    Klebsiella pneumoniae carbapenemase (KPC), Verona integron-coded metallo-beta-lactamase (VIM), OXA-48 (oxacillinase) und New Delhi metallo-beta-lactamase (NDM) are all carbapenemases—enzymes that make bacteria resistant to carbapenems.

  11. 11.

    A bacterium is endemic somewhere if it can be identified there by standard procedures.

  12. 12.

    At ECCMID 2012 it emerged that this was already out of date, since OXA-48 was by then already endemic in Turkey, Morocco, Tunisia and India. For more on the spread of OXA-48 in Europe see for example Albiger et al. (2015) and for the global spread, see e.g. Fursova et al. (2015).

  13. 13.

    If someone is colonised by bacteria they become a carrier. The bacteria multiply, but without causing disease symptoms.

  14. 14.

    4MRGN, multiresistant Gram-negative pathogens (bacilli) with resistance to four antibiotic groups (penicillins, cephalosporins, quinolones, carbapenems).

  15. 15.

    A group of antibiotics that are principally effective against Gram-positive bacteria such as streptococci and pneumococci. The best-known are erythromycin und clarithromycin.

  16. 16.

    Hellenic Centre for Disease Control and Prevention.

  17. 17.

    The European Antibiotic Resistance Surveillance Network is coordinated by the ECDC in Stockholm. Over 900 laboratories from EU countries supply data. They work for 1400 hospitals, which are responsible for approx. 100 million people.

  18. 18.

    Procrustes is a character from Greek mythology. He was an innkeeper who offered his guests food and drink. When they went to bed, he checked that they fitted the bed exactly. If they did not, they were forcibly stretched. However, if there were too long, he cut them down to the correct size by hacking off their limbs. According to Olympia Zartokou, Procrustes’ lack of scruples is a metaphor for the strict measures that are necessary to restrict antibiotics use and antibiotic resistance to an acceptable level once again.

  19. 19.

    Chan was succeeded on the 23th of May 2017 by Dr. Tedros Adhanom Ghebreyesus from Ethiopia as Director General of the WHO.

  20. 20.

    The G8 (Group of Eight) is comprised of the eight richest industrial nations. It was founded in 1975 by the USA, Germany, the UK, France, Italy and Japan as the G6. As a result of Canada’s entry in 1976, it became the G7. Since 1998, Russia has also been taking part, as a result of which it has become the G8. In March 2014, Russia’s membership was suspended during the Crimean crisis.

  21. 21.

    The polymerase chain reaction (PCR) is a test in which very small quantities of genetic material are sufficient to identify a germ quickly.

  22. 22.

    See Chap. 6 The beginning of the end.

  23. 23.

    CP, carbapenemase producing.

  24. 24.

    Personal message from Bart Galloway to the author, 21 February 2014.

  25. 25.

    However, the ‘openness’ of the Nikolaas General Hospital praised by Glupczynski was limited to its openness towards colleagues. There is nothing about the outbreak of bacteria on the hospitals’ website, and the annual reports for 2011 and 2012 do not mention it either.

  26. 26.

    In September 2012, there was also an outbreak of multiresistant Klebsiellas, in which the transfer of patients to the UMC Groningen Beatrixoord rehabilitation centre played a role. The bacterium was introduced into the ward for spinal injuries at the Beatrixoord rehabilitation centre via a patient from the hospital. At both sites, a total of 11 carriers of the bacterium were identified.

  27. 27.

    In 2012, seven hospitals in the province of Liege were affected by KPC. There were outbreaks in three hospitals in which a total of 26 patients were colonised by KPC. Only in one case did a patient bring in the KPC from abroad (Jans et al. 2014).

  28. 28.

    The French data show still very low numbers of Enterobacteriaceae resistant to carbapenems. In 2017, the number was 0.65% for all Enterobacteriaceae, but 1, 56% for Klebsiella pneumoniae. (Santé Publique France 2018).

  29. 29.

    In 2004, Professor Tacconelli was awarded the ESCMID Prize for the nosocomial infections field by the European Society of Clinical Microbiology and Infectious Diseases.

  30. 30.

    Hellenic Centre for Disease Control and Prevention.

  31. 31.

    E-mail message from Olympia Zarkotou to the author on 6 June 2014.

  32. 32.

    Flora Kontopidou in an e-mail to the author on 4 July 2014.

  33. 33.

    Sprenger, at the time director general of ECDC, joined the World Health Organisation in July 2015. He has been Director of the WHO’s Antimicrobial Resistance Secretariat until 2021 and is now Special Envoy Covid-19 Vaccination for the Dutch Carribean.

  34. 34.

    At Essen University Hospital, five transplant patients and two cancer patients became infected with the same Klebsiella pneumoniae with KPC-2 and VIM-1 between July 2010 and January 2011. Five patients developed a severe infection as a result of the bacterium and died. In four cases, the bacterium was the cause. One of the patients who died had been in a Greek hospital shortly before they were first admitted to Essen (Steinmann et al. 2011).

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    Rinke van den Brink

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van den Brink, R. (2021). The End in Sight?. In: The End of an Antibiotic Era. Springer, Cham. https://doi.org/10.1007/978-3-030-70723-1_7

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