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10 September 2018

Superbugs, the New Infectious Threat

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When in 1928 Scottish physician Alexander Fleming discovered penicillin, a new era dawned for medicine that seemed to have eliminated the phantom of bacterial diseases for good. However, in 1945, when receiving the Nobel Prize, Fleming himself warned that the overuse of antibiotics could stimulate the proliferation of resistant microbes, desensitised to the effect of these drugs.

Just over half a century later, that prediction has become a worrying reality: according to a 2014 British study, antibiotic-resistant infections today cause 700,000 deaths a year worldwide, a number that could climb to 10 million by the middle of this century. The culprits behind this threat are usually strains of relatively common bacterial species that develop resistance to multiple antibiotics and are popularly known as superbugs. We review here some of the most dangerous.

MRSA

Scanning electron micrograph of methicillin-resistant Staphylococcus aureus and a dead human neutrophil. Credit: NIAID

The bacteria Staphylococcus aureus resistant to methicillin (MRSA) was one of the earliest superbugs to be recognised, first detected in the early 1960s in the United Kingdom. Methicillin was at that time used to treat resistant infections, and various strains of S. aureus—a bacteria common in the microbial flora of humans that usually only causes minor infections—that did not respond to various beta-lactam antibiotics, the most commonly used, began to be grouped under the name MRSA. Since then, MRSAs have become a common source of serious hospital infections, and are also frequently present in the general population.

Clostridium difficile

Micrograph of the bacterium Clostridium difficile. Credit: CDC / Dr. Gilda Jones

A special case on this list is Clostridium difficile. While most superbugs are variants that have acquired resistance to antibiotics, in this case it’s a species that lives up to its name due to the difficulty of its treatment and eradication. C. difficile is present in the intestinal flora of a small percentage of the population. While it usually doesn’t cause problems, antibiotic treatments can lead to its proliferation by eliminating its weakest competitors. In these cases it can cause severe diarrhoea, intestinal damage and sepsis, especially in elderly people. The bacterium is transmitted by faecal contamination thanks to its spores, which are resistant to disinfection with alcohol.

Bacteria resistant to carbapenems

Colorized scanning electron micrograph showing carbapenem-resistnt Klebsiella pneumoniae interacting with a human neutrophil. Credit: NIAID

In 2017 the World Health Organization (WHO) published a document in which it listed the superbugs against which it is most urgent to develop new antibiotics. The category designated as being of critical priority brought together three groups of species different from each other, but with two common features. First, the Acinetobacter baumannii, the Pseudomonas aeruginosa and the Enterobacteriaceae family are all Gram-negative bacteria, so called because of the presence of a double cell membrane that does not stain with the so-called Gram stain and that hinders the action of antibiotics. Second, these three groups include variants resistant to carbapenems, a type of potent antibiotic that is usually held back as a last resort when all others have failed. Last April, the US Center for Disease Control (CDC) reported the detection in that country in 2017 of more than 200 strains of these microbes that the agency calls “nightmarish bacteria.” Recently, a strain resistant to carbapenems of the bacterium Klebsiella pneumoniae has been described that also resists colistin, an antibiotic that is only used in desperate cases due to its toxicity to the kidney.

VRE

Scanning Electron Micrograph of Vancomycin Resistant Enterococci. Credit: Janice Haney Carr

Enterococci, such as Enterococcus faecium, are another example of bacteria that live with us as part of our normal digestive flora without causing damage, but which can sometimes invade the bloodstream and colonize other tissues, causing serious infections. In the 1980s, the first strains appeared (known as VRE) that were resistant to vancomycin, an antibiotic that is given intravenously to fight complicated infections such as those caused by MRSA. VREs are in the high priority category for the development of new antibiotics on the WHO list. A recent study in Australia has found that numerous circulating strains of VRE are also acquiring resistance to the alcohol present in hand sanitizers used in hospitals.

Resistant gonorrhoea

Colorized scanning electron micrograph of Neisseria gonorrhoeae bacteria, which causes gonorrhea. Credit: NIAID

Gonorrhoea, a sexually transmitted disease caused by the bacterium Neisseria gonorrhoeae, has been treated effectively with antibiotics for decades, but resistant strains that are difficult to treat have emerged recently, which has led the WHO to place it in the high priority category. One of the most recent cases was described last May in the United Kingdom: a man who had contracted the disease in Southeast Asia and who did not respond to treatment with any of the common antibiotics. In the end he was cured after three days of intravenous administration of ertapenema, an antibiotic of last resort from the carbapenem group.

Resistant tuberculosis

The bacterium Mycobacterium tuberculosis. Credit: Janice Haney Carr, Dr. Ray Butler, USCDCP

Curiously, the WHO’s list of superbugs omitted tuberculosis, a disease that in developed countries is often associated with past epochs, but which this organization lists as one of the top 10 causes of death in the world, with more than 10 million cases and 1.7 million deaths in 2016. The reason for this omission is not the lack of concern about this infection, but quite the opposite: it had already previously been designated as the top priority in the search for new antibiotics. The multi-resistant antibiotic strains of the bacterium Mycobacterium tuberculosis (MDR-TB) are currently a threat to global health, which in 2016 affected half a million people, especially in India, China and Russia. The disease is especially severe in patients with weakened defences, such as carriers of the human immunodeficiency virus (HIV).

Multi-resistant Staphylococcus epidermidis

Scanning electron micrograph of two staphylococcus epidermidis bacteria. Credit: Janice Haney Carr, Dr. Ray Butler, USCDCP

One of the last superbugs to date in the scientific literature is another species of staphylococcus, S. epidermidis, also a common inhabitant of healthy human skin. In September 2018, a study conducted by the University of Melbourne (Australia) described three strains of this bacterium that evade the action of the most common drugs, but also show increasing resistance to antibiotics of last resort such as vancomycin. Researchers have located these variants in samples from 24 countries, which suggests that in future years this staphylococcus could become an even more dangerous enemy than its relative: MRSA.

Javier Yanes

@yanes68

 

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