Antimicrobial Efficacy of Revived Antibiotics

Antimicrobial resistance continues to undermine the effectiveness of existing drug pipelines, prompting renewed interest in older agents that were once set aside. Revived antibiotics encompass a spectrum of legacy compounds—from β‐lactams such as temocillin to polymyxins, fosfomycin, nitrofurantoin and chloramphenicol—re‐evaluated in light of modern resistance mechanisms and stewardship imperatives. By exploiting their retained activity against multidrug‐resistant Gram‐negative and Gram‐positive pathogens, these drugs can spare last-line therapies, reduce selective pressure on newer agents and offer cost-effective options in resource-limited settings. Advances in pharmacokinetic/pharmacodynamic (PK/PD) modelling have refined dosing regimens, while combination strategies reveal synergistic effects that curtail the emergence of resistance. Mechanistic insights into efflux systems, porin mutations and biofilm physiology underpin targeted use of these antibiotics, guiding clinical practice from outpatient parenteral antimicrobial therapy (OPAT) to intensive care. With a global footprint spanning community and hospital contexts, revived antibiotics now feature in precision-driven therapy, integrating molecular diagnostics with dose optimisation. Their resurgence underscores a pragmatic approach to antimicrobial stewardship and highlights the importance of bridging fundamental microbiology with translational research to maintain durable treatment options against evolving pathogens.

Research from Nature Portfolio

Recent studies have redefined intrinsic barriers to temocillin efficacy in Pseudomonas aeruginosa isolates from cystic fibrosis patients. A comprehensive survey of clinical strains revealed that mutations in the MexAB-OprM efflux pump—previously implicated in β-lactam exclusion—can reverse intrinsic resistance, yielding clinically exploitable minimum inhibitory concentrations. Correlations between specific mexA/mexB alterations, efflux rates and exopolysaccharide production illuminate the complex interplay between bacterial physiology and drug susceptibility. These findings reinvigorate temocillin’s potential in settings where extended-spectrum β-lactamases have eroded first-line options and establish a paradigm for targeting efflux machinery to resurrect legacy antibiotics.

Antimicrobial Efficacy of Revived Antibiotics publication trend

The graph below shows the total number of articles in antimicrobial efficacy of revived antibiotics across all publications each year (not limited to Nature Index journals).

Technical terms

Minimum inhibitory concentration (MIC): The lowest antibiotic concentration that prevents visible bacterial growth in vitro.

Extended-spectrum β-lactamase (ESBL): Enzymes produced by bacteria that confer resistance to most β-lactam antibiotics.

Efflux pump: A membrane protein complex that expels antibiotics from bacterial cells, reducing intracellular drug concentration.

Synergy: Enhanced antimicrobial effect observed when two or more drugs act together more effectively than the sum of their individual effects.

Pharmacokinetics/pharmacodynamics (PK/PD): The study of drug absorption, distribution, metabolism and excretion (PK) coupled with the drug’s biological effects (PD) to optimise dosing.

References

1. A new strategy to fight antimicrobial resistance: the revival of old antibiotics. Frontiers in Microbiology (2014).
2. Clinical Efficacy of Temocillin Standard Dosing in Patients Treated with Outpatient Antimicrobial Therapy. Pharmaceutics (2022).
3. Assessing Clinical Potential of Old Antibiotics against Severe Infections by Multi-Drug-Resistant Gram-Negative Bacteria Using In Silico Modelling. Pharmaceuticals (2022).
4. Mechanisms of intrinsic resistance and acquired susceptibility of Pseudomonas aeruginosa isolated from cystic fibrosis patients to temocillin, a revived antibiotic. Scientific Reports (2017).
5. Clinical and microbiological evaluation of temocillin for bloodstream infections with Enterobacterales: a Belgian single-centre retrospective study. JAC-Antimicrobial Resistance (2022).