**Background:** Biofilms are structured communities of microorganisms encased in a self-produced extracellular polymeric substance (EPS) that adhere to biotic or abiotic surfaces. They are responsible for approximately 70% of all human microbial infections and are a major contributor to healthcare-associated infections (HAIs). Biofilms exhibit extreme resistance to antimicrobial agents—up to 1000-fold greater than planktonic bacteria—due to mechanisms such as reduced drug penetration, altered microenvironment, slow growth rates, and horizontal gene transfer. This review provides a comprehensive overview of biofilm formation, associated infections, antibiotic resistance mechanisms, and current and emerging control strategies.
**Methods:** This is a narrative review that synthesizes existing literature on biofilm biology, clinical infections, and therapeutic approaches. The authors describe the stages of biofilm formation (initial attachment, adhesion/aggregation, microcolony formation, maturation, and dispersion) and the role of quorum sensing (QS) in coordinating these processes. They also review data on biofilm-related infections from medical devices (urinary catheters, central venous catheters, prosthetic heart valves, contact lenses, intrauterine devices, dental unit water lines) and non-device infections (periodontitis, osteomyelitis, chronic wounds). The paper evaluates conventional antibiotics, small molecules, QS inhibitors, monoclonal antibodies, natural products, probiotics, gene editing (CRISPR-Cas), and anti-infective device coatings as control measures.
**Key Results:** The review reports that biofilms consist of 10% microbial mass and 90% water, with polysaccharides comprising 50–90% of the organic component. Biofilm thickness can reach up to 300 µm. The most common biofilm-forming bacteria include *Pseudomonas aeruginosa*, *Staphylococcus epidermidis*, *Escherichia coli*, *Klebsiella pneumoniae*, *Proteus mirabilis*, *Streptococcus viridans*, *Staphylococcus aureus*, and *Enterococcus faecalis*. Staphylococci are responsible for nearly 80% of implantable device infections. Catheter-associated urinary tract infections (CAUTIs) occur in 10–50% of patients with short-term catheterization (<7 days) and essentially all patients with long-term catheterization (>28 days). The attributable cost of CAUTI exceeds $1,000 per patient, with an annual economic loss of approximately $1.7 billion. Biofilm bacteria show 10- to 1000-fold increased antibiotic resistance; for example, 75% of *S. epidermidis* biofilm isolates were resistant to vancomycin, while planktonic isolates were sensitive. Quorum sensing inhibitors (e.g., FABHL, CABHL) and monoclonal antibodies (e.g., TRL1068) have shown promise in preclinical models. Natural products such as andrographolide, emodin, and sodium houttuyfonate inhibit biofilm formation by downregulating virulence genes. Probiotics like *Bifidobacterium* and *Enterococcus faecium* prevent biofilm development through anti-adhesion and QS-suppression mechanisms. CRISPR-Cas systems have been used to target antibiotic resistance genes in *E. coli* and *S. aureus* biofilms.
**Clinical Implications:** Biofilm-associated infections pose a significant challenge due to their high resistance to conventional antibiotics. The review emphasizes that early intervention is critical, as younger biofilms are more susceptible to antimicrobials. Preventive strategies include surface engineering, antimicrobial coatings (e.g., silver alloy, nitrofurazone), and strict adherence to catheter insertion and removal protocols. For established biofilms, combination therapies—such as antibiotics with QS inhibitors or monoclonal antibodies—may enhance efficacy. The use of anti-infective catheters is recommended for high-risk patients, though evidence for reduced mortality is lacking. Future research should focus on quorum quenching, dispersal agents, and gene editing to overcome biofilm resistance. The review underscores the need for multidisciplinary approaches to translate these strategies into clinical practice.