Antimicrobial Strategies for Skin and Soft Tissue Infections

Skin and soft tissue infections (SSTIs) encompass a spectrum from superficial impetigo and cellulitis to deep abscesses and necrotising fasciitis. Staphylococcus aureus and Streptococcus pyogenes remain the predominant pathogens, with the rise of methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug-resistant organisms posing ongoing challenges. Current management strategies combine prompt surgical intervention—such as drainage and debridement—with systemic antimicrobial therapy. Traditional agents include beta-lactams, lipopeptides and glycopeptides, while newer fluoroquinolones and lipoglycopeptides extend the spectrum or improve dosing convenience. Optimised dosing guided by pharmacokinetic and pharmacodynamic principles is critical to ensure adequate tissue penetration and minimise toxicity, particularly in patients with altered physiology. Adjunctive approaches such as antimicrobial dressings, topical antiseptics and negative-pressure wound therapy can disrupt biofilms and enhance local drug delivery. Cutting-edge research explores efflux pump inhibitors to restore antibiotic efficacy, dual-target agents designed to slow resistance, and nanoparticle-based carriers for targeted delivery. Together, these strategies form a multifaceted arsenal aimed at improving outcomes, curbing resistance and addressing the global burden of SSTIs.

Research from Nature Portfolio

Recent studies have uncovered novel resistance pathways in MRSA exposed to dual-targeting fluoroquinolones. Rather than accumulating mutations in both DNA gyrase and topoisomerase IV, MRSA can amplify regions encoding an uncharacterised efflux pump, leading to high-level resistance and unexpected cross-resistance to other antibiotics. This finding emphasises the need to consider efflux mechanisms when developing agents that target multiple bacterial enzymes.

Antimicrobial Strategies for Skin and Soft Tissue Infections publication trend

The graph below shows the total number of articles in antimicrobial strategies for skin and soft tissue infections across all publications each year (not limited to Nature Index journals).

Technical terms

Efflux pump: A membrane transporter that expels antibiotics from bacterial cells, reducing intracellular drug concentration and contributing to resistance.

Minimum inhibitory concentration (MIC): The lowest concentration of an antimicrobial that prevents visible growth of a microorganism in vitro.

Pharmacokinetics (PK): The study of how a drug is absorbed, distributed, metabolised and excreted over time.

Pharmacodynamics (PD): The relationship between drug concentration at the site of action and the resulting antimicrobial effect.

Topoisomerase IV: A bacterial enzyme essential for DNA decatenation during replication and a key target of fluoroquinolone antibiotics.

Methicillin-resistant Staphylococcus aureus (MRSA): A strain of S. aureus that carries resistance to all beta-lactam antibiotics, complicating standard therapy.

References

1. Efflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic. Nature Communications (2023).
2. Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization. Antimicrobial Agents and Chemotherapy (2024).
3. New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians. Pharmaceuticals (2023).
4. Investigating the Antibacterial Effects of Synthetic Gamma-Lactam Heterocycles on Methicillin-Resistant Staphylococcus aureus Strains and Assessing the Safety and Effectiveness of Lead Compound MFM514. Molecules (2023).