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Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
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Antibiotic failure: Beyond antimicrobial resistance.

Cesar de la Fuente-Nunez1, Angela Cesaro1, Robert E W Hancock2

  • 1Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|November 4, 2023
PubMed
Summary

Antimicrobial treatment failure, not just resistance, causes millions of deaths. Understanding factors like biofilms and sepsis is crucial for developing new therapies beyond antibiotics to combat persistent infections.

Keywords:
Antibiotic resistanceBiofilmGlobal healthInfectious DiseasesSepsis

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Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Millions die annually from infections, with treatment failures surpassing genetic resistance.
  • Antibiotic failure is a critical, under-recognized issue in clinical settings.
  • Biofilms and sepsis significantly contribute to treatment ineffectiveness.

Purpose of the Study:

  • To elucidate mechanisms of clinical antimicrobial therapy failure beyond antibiotic resistance.
  • To highlight the impact of biofilms, sepsis, and microbiome on treatment outcomes.
  • To explore non-antibiotic therapeutic strategies for addressing antibiotic failure.

Main Methods:

  • Literature review focusing on fundamental mechanisms of antibiotic failure.
  • Analysis of factors including biofilm formation, sepsis, and microbiome.
  • Examination of current and novel therapeutic strategies.

Main Results:

  • Multidrug adaptive resistance in biofilms (65% of infections) lacks approved therapies.
  • Sepsis, causing 19.7% of deaths, shows high mortality (23%) despite antibiotic use.
  • Antibiotic failure is a significant crisis due to limited therapies and potential ineffectiveness of new drugs.

Conclusions:

  • Urgent need for novel anti-infectives and host-directed therapies to address antibiotic failure.
  • Addressing biofilm resistance and sepsis management is critical for improving patient outcomes.
  • Rethinking therapeutic strategies beyond conventional antibiotics is essential.