The war against bacteria, from the past to present and beyond

ABSTRACT

Introduction

The human defense against microorganisms dates back to the ancient civilizations, with attempts to use substances from vegetal, animal, or inorganic origin to fight infections. Today, the emerging threat of multidrug-resistant bacteria highlights the consequences of antibiotics inappropriate use, and the urgent need for novel effective molecules.

Methods and Materials

We extensively researched on more recent data within PubMed, Medline, Web of Science, Elsevier’s EMBASE, Cochrane Review for the modern pharmacology in between 1987 - 2021. The historical evolution included a detailed analysis of past studies on the significance of medical applications in the ancient therapeutic field.

Areas covered

We examined the history of antibiotics development and discovery, the most relevant biochemical aspects of their mode of action, and the biomolecular mechanisms conferring bacterial resistance to antibiotics.

Expert opinion

The list of pathogens showing low sensitivity or full resistance to most currently available antibiotics is growing worldwide. Long after the ‘golden age’ of antibiotic discovery, the most novel molecules should be carefully reserved to treat serious bacterial infections of susceptible bacteria. A correct diagnostic and therapeutic procedure can slow down the spreading of nosocomial and community infections sustained by multidrug-resistant bacterial strains.

KEYWORDS:

• Microbiology
• history of medicine
• history of pharmacology
• antibiotics
• antibiotic resistance

Author contributions

All the authors equally contributed for conceptualization, writing and final approval of the manuscript. L Bottalico and I Alexandros Charitos collected, analyzed, and discussed the historical features discussed here, MA Potenza and M Montagnani accounted for the pharmacological and biochemical data, and L Santacroce for the microbiological insights. M Montagnani and L Santacroce provided resources and financial support for this study.

Article highlights

• Antibiotics include natural substances (mainly produced in actinomycetes and fungi, soil samples, plants, marine organisms), semi-synthetic derivatives modified from the original compounds, or molecules synthetically produced.

• Antimicrobial therapy is a strategy to counteract infections intended to selectively destroy or inhibit pathological microbial development, without altering the function or damaging the structure of host cells (selective cell toxicity).

• Over the years, biomolecular mechanisms underlying the anti-infective activity of antibiotics have been identified. The correct choice of an antibiotic must take into account multiple factors that aim for a better and lasting efficacy of antimicrobial therapy.

• Misuse of antibiotics represents a major cause for selection of mutations responsible for the antibiotic resistance. It includes (but it is not limited to) empirical use (treatment of a disease from unknown etiological agents), prophylaxis in surgery, inappropriate use of molecules with a broad spectrum of action, auxinic use in farm animals, administration in pediatric patients with viral infections and improper patient compliance.

• One of the biggest and urgent challenges today is the development of effective novel molecules to counteract antibiotic resistance.

• The antibiogram remains an extremely useful method to guide the correct treatment in single patients, to help identify antibiotic-resistant hospital infections, and for epidemiological purposes.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.