Antibiotic resistance in bacteria (Barta et al. 2021)
Traditional thought/background
Hypothesis
Bacteria evolve to resist antibiotics, but evolution is not favored when the environment and selection conditions are not stable.
Using multiple antibiotics with a similar mechanism of action promotes cross resistance and worsens the resistance problem.
Could exposing bacteria to sequentially different antibiotics slow the evolutionary process?
Works cited
Aditi Batra, Roderich Roemhild, Emilie Rousseau, Sören Franzenburg, Stefan Niemann, Hinrich Schulenburg. High potency of sequential therapy with only β-lactam antibiotics. eLife, 2021; 10
Rhee C, Kadri SS, Dekker JP, Danner RL, Chen H-C, Fram D, Zhang F, Wang R, Klompas M, CDC Prevention Epicenters Program. 2020. Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use. JAMA Netw Open. 3(4):e202899.
Methods
P. aeruginosa with bacterial resistance were sequentially exposed to different antibiotics within the same class (same mechanism of action).
Arm 1
Arm 2
β-lactams (carbenicillin, doripenem and cefsulodin)
non β-lactams
Reaction
Very exciting results. The prospect of using different antibiotics within the same class to treat antibiotic resistant bacteria within that class would represent a novel approach in medicine. This is especially relevant because the alternative would be treating these infections with broad spectrum antiobiotics which is actually associated with worse outcomes and increased mortality (Rhee et al. 2020).
Results
Based on growth and genome sequence, the β-lactam arm had more effective antibacterial activity than the arm of antibiotics with differing mechanisms of action. Surprising, because antibiotics within the same class should be selective enough to accelerate the selection for and evolution of bacteria with antibiotic resistant properties.
Further, quickly switching between different β-lactams resulted in higher antibiotic activity than exposing the bacteria to a single agent, suggesting that this inhibited the further evolution of the bacteria's antibiotic resistance.
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Discussion
Colatteral sensitivity
Development of antibiotic resistance to doripenem was lower when treated with other drugs in the β-lactam sequence. Even when bacteria develop resistance to drugs with the same mechanism of action given later in the sequence, they remain susceptible to drugs given earlier in the sequence such as doripenem.
This colatteral sensitivity is an important component in treating these infections of antibiotic resistant bacteria. Resistance to one drug within a class does not mean the bacteria would be resistant to other drugs within the same class.