Alarming Increase of Antimicrobial Resistance: Prioritization of Bacterial Targets for Research by the WHO

According to the World Health Organization (WHO), antimicrobial resistance (AMR) is a growing threat to global public health undermining effective prevention and treatment of disease caused by bacteria, parasites, viruses, and fungi.1

Without effective antibiotics:

  • Major surgeries such as caesarean section, organ transplants, hip replacements, and chemotherapy become riskier
  • More tests and use of costlier drugs are needed
  • Illnesses are prolonged which may result in worse clinical outcomes
  • The fight against HIV, TB, and malaria is complicated

The rate of AMR is being accelerated by the misuse and overuse of antibiotics in humans, utilization as growth promoters, or to prevent diseases in healthy animals. Poor infection control, unsanitary conditions, and improper handling of food also contribute to the spread of AMR.

 Acquired Resistance in Specific Bacteria

Klebsiella pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns, and in intensive care unit (ICU) patients. This common intestinal bacterium has developed resistance to a class of antibiotics, carbapenems, throughout the world.

Escherichia coli is another common intestinal bacterium that has developed widespread resistance to fluoroquinolone antibiotics used to treat urinary tract infections

Cephalosporins are last line of defense against gonorrhea but bacterial resistance has been confirmed in several countries including Australia, Austria, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden, U.K, and Northern Ireland. Such growing resistance has prompted the WHO to update treatment guidelines for gonorrhea, syphilis, and chlamydial infections.

Resistance to first-line drugs to Staphylococcus aureus, a common cause of severe infections in health facilities and the community, is widespread. Mortality rates of people with methicillin-resistant S. aureus (MRSA) is 64% higher than people with a non-resistant form of the infection.

Colistin is the treatment of last resort for life-threatening infections caused by Enterobacteriaceae which are already resistant to carbapenems. Resistance to colistin has been detected in several countries, making infections untreatable.

WHO estimates that, in 2014, there were about 480,000 new cases of multidrug-resistant tuberculosis (MDR-TB), a form of tuberculosis that is resistant to the two most powerful anti-TB drugs. Extensively drug-resistant tuberculosis (XDR-TB), which is resistant to at least four anti-TB drugs, has been identified in 105 countries.

As of July 2016, resistance to the first-line treatment for Plasmodium falciparum malaria has been confirmed in 5 countries (Cambodia, the Lao People’s Democratic Republic, Myanmar, Thailand, and Vietnam). Along the Cambodia-Thailand border, P. falciparum has become resistant to almost all available antimalarial medicines.

To protect public health, there is a need for coordinated action between countries, scientists, and governmental bodies. WHO is providing technical assistance to help countries develop their national action plans and strengthen their health and surveillance systems to more effectively prevent and manage antimicrobial resistance. WHO has established multiple initiatives to address antimicrobial resistance, e.g., World Antibiotic Awareness Week has been held every November since 2015.

Member states have asked the WHO to identify the most important resistant bacteria globally in terms of urgency for new treatments and to guide prioritization of incentives and funding for public health needs.2 Mycobacterium tuberculosis was not discussed because its urgent need has previously been established. Criteria for prioritization included all-cause mortality, healthcare and community burden, prevalence and 10-year trend of resistance, transmissibility, preventability, treatability, and current pipeline.

A group of 70 experts stratified the results in three priority tiers: critical, high, and medium.

Priority 1: CRITICAL

  • Acinetobacter baumannii, carbapenem-resistant (gram-negative)
  • Pseudomonas aeruginosa, carbapenem-resistant (gram-negative)
  • Enterobacteriaceae which include K. pneumonia, E. coli, Enterobacter spp., Serratia spp., Proteus spp.,
  • Providencia spp., Morganella spp., carbapenem-resistant, 3rd generation cephalosporin-resistant (gram-negative)

Priority 2: HIGH

  • Enterococcus faecium, vancomycin-resistant (gram-positive)
  • S aureus, methicillin-resistant, vancomycin intermediate and resistant (gram-positive)
  • Helicobacter pylori, clarithromycin-resistant (gram-negative)
  • Campylobacter spp., fluoroquinolone-resistant (gram-negative)
  • Salmonella spp., fluoroquinolone-resistant (gram-negative)
  • Neisseria gonorrhoeae, 3rd generation cephalosporin-resistant, fluoroquinolone-resistant (gram-negative)

Priority 3: MEDIUM

  • Streptococcus pneumoniae, penicillin-non-susceptible (gram-positive)
  • Haemophilus influenzae, ampicillin-resistant (gram-positive)
  • Shigella spp., fluoroquinolone-resistant (gram-negative)
The list shows gram-negative bacteria (top 3) as a critical priority. It is vital for the scientific community to continue improving understanding of mechanisms bacteria use to acquire resistance and to develop new antibiotics against multidrug- and extensively drug-resistant pathogens.

   

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References

  1. WHO guidelines on use of medically important antimicrobials in food-producing animals. 2017. http://www.who.int/antimicrobial-resistance/en/
  2. Global priority list of antibiotic-resistant bacteria to guide research, discovery and development of new antibiotics. World Health Organization. 2017. http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb ET_NM_WHO.pdf