COVID-19 has dominated mainstream attention, and the race to roll out safe and effective vaccines was impressive. However, the serious threat of antibiotic resistance persists, even though it may have lost some much-needed attention during the pandemic.

While COVID-19 is responsible for claiming more than 5.6 million lives, estimates claim that the death toll from the antimicrobial resistance crisis will reach 10 million per year by 2050. 

Global burden of antimicrobial resistance

In a 2022 article published in The Lancet, researchers assessed the global burden associated with drug-resistant infections in 2019 by examining 88 pathogen–drug combinations, with a focus on bacterial infections. 

They estimated that in 2019, drug-resistant infections caused 4.95 million deaths worldwide. Of these deaths, 1.27 millions deaths were attributed to drug resistance—surpassing the death toll caused by both HIV and malaria. 

Investigators then identified the six deadliest bacterial pathogens responsible for nearly three-quarters of all deaths attributed to antimicrobial resistance, including Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Methicillin-resistant Staphylococcus aureus alone was responsible for more than 100,000 deaths in 2019. 

COVID-19 and antibiotic resistance 

The COVID-19 pandemic has placed an immense burden on our healthcare system, with the potential for repercussions for years to come. One such outcome is the impact COVID-19 has had on antibiotic resistance, with public health experts concerned that COVID-19 has only made matters worse. 

According to an article published in eLife, as many as 70% of COVID-19 patients received antimicrobials in both the outpatient and inpatient settings for two main reasons: First, their symptoms often resembled bacterial pneumonia, and diagnostic tests that distinguish between bacterial and viral pneumonia are typically ineffective or have long turnaround times. 

Secondly, COVID-19 patients could have acquired secondary co-infections, requiring antimicrobial treatment. This increase in antimicrobial use could give way to a rise in drug resistance. 

The caveat, however, is that the COVID-19 pandemic also led to better hygiene practices, decreased international travel, and decreased elective hospital procedures—all of which may reduce antimicrobial resistance in the short term. 

COVID-19 and antimicrobial research 

Accompanying the substantial increase in COVID-19 research starting in 2020, there is likely to have been a considerable decrease in antimicrobial drug research, according to the eLife article. Certain equipment, such as PCR machines and reagents, were redirected toward COVID-19 research. 

In addition, travel restrictions limited the ability of antimicrobial researchers to continue their efforts, leading to interruptions of much-needed programs. The pandemic has also led to a gap in global monitoring of antimicrobial resistance. For example, many routine microbiology samples that are typically used for monitoring antimicrobial resistance will be missing some data for 2020. 

Current drug discovery status 

In April 2021, the WHO released its 2020 annual review of the clinical and preclinical antibacterial pipeline, which evaluated antibacterial agents in different stages of development.

There are currently 43 antibiotics in the clinical antibacterial pipeline, as well as 27 non-traditional antibacterial agents, which include antibodies and phage-derived enzymes. Of the 43 antibiotics, 12 are active against Mycobacterium tuberculosis, five are active against Clostridium difficile, and 26 are active against the WHO priority pathogens. 

However, while there is a good number of antibacterial agents in development, only seven of the 26 antibiotics with activity against the WHO priority pathogens fulfill at least one of WHO’s innovation criteria, and only two show activity against multidrug-resistant (MDR) Gram-negative bacteria. 

There is also a critical gap in activity against metallo-β-lactamase (MBL) producers, with 40% of the 26 antibiotics being β-lactams and β-lactamase inhibitor (BLI) combinations. 

Recent approvals 

Since July 2017, 11 new antibiotics have been approved for use, according to the WHO’s 2020 review. 

Unfortunately, these newly approved drugs do not offer much benefit over current drugs, as the majority (nine of 11) are from existing classes of drugs where mechanisms of resistance are already well-documented. For these agents, the emergence of resistance is expected to be rapid, rendering these drugs ineffective in a short time. 

According to the WHO, “Overall, the clinical pipeline and recently approved antibiotics are insufficient to tackle the challenge of increasing emergence and spread of antimicrobial resistance. ”

One notable exception is cefiderocol, the first siderophore-conjugated antibiotic to make it past phase 1 clinical trials. Cefiderocol is active against drug-resistant bacteria as well as Gram-negative pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii. 

Sources 

1. 2020 antibacterial agents in clinical and preclinical development: an overview and analysis. WHO. 2021. 

2. Else H. How a torrent of COVID science changed research publishing — in seven charts. Nature. 2020;588(7839):553-553.

3. Knight GM, Glover RE, McQuaid CF, et al. Antimicrobial resistance and COVID-19: Intersections and implications. eLife. 2021;10:e64139.

4. Murray CJ, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022;399(10325):629-655.