Macrolides at Clinically-Relevant Concentrations May Induce Biofilm Formation in Macrolide-Resistant Staphylococcus...

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Antimicrobial Resistance

Background:

• Macrolides are known to inhibit biofilm formation in Gram-negative bacteria.
• The impact of macrolides on biofilm formation in susceptible Gram-positive bacteria is less understood due to growth-inhibitory concentrations.
• Macrolide resistance mechanisms in Staphylococcus aureus include target modification and efflux pumps.

Purpose of the Study:

• To investigate the effect of sub-inhibitory concentrations of macrolides (erythromycin, clarithromycin, azithromycin) on biofilm formation in macrolide-resistant Staphylococcus aureus isolates.
• To explore how different resistance mechanisms influence the interaction between macrolides and S. aureus biofilm development.

Main Methods:

• Utilized the crystal violet assay in 96-well plates to quantify biofilm formation.
• Tested macrolide concentrations ranging from 0.5-2 µg/mL.
• Examined biofilm formation at early (4 h) and later (8 and 12 h) incubation times across various S. aureus isolates with different resistance profiles.

Main Results:

• Macrolides consistently induced early biofilm formation in S. aureus strains with constitutive target-modification resistance.
• Azithromycin did not induce biofilm formation in longer incubation periods (8 and 12 h) for these strains.
• Inducible resistance isolates showed enhanced early biofilm formation with macrolide treatment, but premature biofilm decay at later stages.
• Biofilm formation in efflux-mediated resistant isolates remained unaffected by macrolides.

Conclusions:

• Macrolides can induce biofilm formation in resistant Staphylococcus aureus isolates, particularly during early developmental stages.
• Empirical use of macrolides against resistant S. aureus may lead to clinical failure and increased biofilm formation, complicating treatment.
• Understanding macrolide-resistance interplay is crucial for effective therapeutic strategies against S. aureus infections.