Abstract
Antibiotic resistance has always existed all over the world. It sounds paradoxical, but there was resistance to antibiotics before human beings began producing them. The reason for this is that many antibiotics occur in nature and are based on natural ingredients. Drivers of antimicrobial resistance may differ in varying situations. In wealthy countries, in the richer parts of the world overuse of antibiotics may be the main driver of resistance. In low and middle-income countries underuse and poor access to antibiotics may play a role. The availability of penicillin has had a very significant impact on the mortality of the population, of a kind never achieved by any other medicine. However, the mortality caused by infectious diseases had already dramatically decreased before the introduction of penicillin and later other antibiotics. The most important contribution to the decrease of mortality due to infectious diseases has been sanitation. Clean drinking water, (individual) toilets, sewer systems and waste water treatment contributed more to it than anything else. Newly spreading forms of antimicrobial resistance may in the long run evolve to the appearance of pan-resistant bacteria that are capable of causing untreatable infections.
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Notes
- 1.
Beta-lactam antibiotics kill bacteria by upsetting the synthesis of the bacterial cell wall, which then dissolves. The group of beta-lactam antibiotics includes penicillins, cephalosporins, carbapenems and monobactams. Because of their low toxicity and outstanding efficacy against bacteria that react to them, they are frequently used. Resistances against beta-lactam antibiotics are often found together with resistances against other antibiotics. In such cases there are few other effective agents to choose from, but these are preferably not used since they are either toxic, less effective or both.
- 2.
Vancomycin, a member of the class of glycopeptides, is a natural antibiotic which works by destabilising the bacterial cell wall. Vancomycin is administered for infections that have been caused by methicillin-resistant staphylococcus aureus (MRSA), methicillin-resistant staphylococcus epidermidis (MRSE) and Clostridium difficile.
- 3.
Virulence genes determine how intensely pathogenic a bacterium is.
- 4.
Campylobacter is a family of bacteria that cause the most frequently occurring zoonoses, i.e. diseases that can be transmitted from animals to humans. For many animals—including poultry, livestock, birds, cats, young dogs and rodents—the bacterium is a normal intestinal bacterium. The bacteria are also transmitted by flies and they are also present in ground and surface water. The infection can result in acute, aqueous and occasionally bloody diarrhoea, accompanied by severe stomach cramps and, sometimes, fever. Very small children, older people, those infected with HIV and patients with impaired immunity are most at risk of severe complications. In 2017, more than 250,000 laboratory-confirmed cases of campylobacteriosis in EU/EEA countries were reported to the ECDC. This is equivalent to 64.9 cases per 100,000 members of the population, an increase compared to the 60.8 cases per 100.000 in 2013. Children below the age of 5 years are most susceptible to campylobacteriosis (ECDC 2019).
- 5.
In June 2012, the World Health Organisation (WHO) warned that it would become more difficult to treat gonorrhoea because the bacteria that cause the disease are becoming increasingly resistant to antibiotics. Cases of gonorrhoea that were resistant to cephalosporins—the last antibiotic available to treat this sexually transmitted disease—have already been reported In Australia, Japan, France, Norway, Sweden and the United Kingdom. Also in June 2012, the European Centre for Disease Prevention and Control (ECDC) published an action plan (ECDC 2012b).
- 6.
Mortality figures that have been corrected to reflect the composition of the population in terms of age and gender.
- 7.
These categories are used by the World Bank. According to the World Bank website ‘for the current 2021 fiscal year, low-income economies are defined as those with a Gross National Income (GNI) per capita, calculated using the World Bank Atlas Method, of $ 1035 or less in 2019; lower middle-income economies are those with a GNI per capita between $ 1036 and $ 4045.
- 8.
When an antibiotic is administered to a patient this drug neutralises or kills microbes that are sensitive to its working, while those resistant stay alive and can procreate without the competition of the neutralised and killed microbes. This mechanism is called selection pressure.
- 9.
Beta-lactam antibiotics, aminoglycosides, (fluoro-) quinolones, vancomycin, rifampicin, nitroimidazole derivatives and sulphonamides/trimethoprim are bactericidal medicines. Tetracycline, macrolides, chloramphenicol and thiamphenicol have bacteriostatic effects.
- 10.
The Danish microbiologist Hans Christian Gram (1853–1938) developed the Gram staining technique, which enables types of bacteria to be distinguished by staining them with crystal violet iodine complex, decolouring them with alcohol, and counterstaining them with fuchsin. Gram-negative bacteria are coloured red, and Gram-positive bacteria appear bluish-violet.
- 11.
Colistin belongs to the family of polymixins, a group of polypeptide antibiotics discovered in 1947. They have broad-spectrum activity against Gram-negative bacteria, including most species of the Enterobacteriaceae family. The two polymyxins currently in clinical use are polymyxin B and polymyxin E (colistin), which differ from one another by one amino acid only, and have comparable biological activity.
- 12.
Enterobacteriaceae or enterobacter are a family of Gram-negative bacteria, the most frequently occurring of which are E. coli and Klebsiella spp. ‘spp.’ stands for ‘species’(plural).
- 13.
ARBs = antibiotic resistant bacteria, ARGs = antibiotic resistance genes.
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van den Brink, R. (2021). In the Beginning There Was Antibiotic Resistance. In: The End of an Antibiotic Era. Springer, Cham. https://doi.org/10.1007/978-3-030-70723-1_2
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