Table 1.

Bacteria biofilm contribution in the antibiotic’s inactivation and antibiotic treatment failure.

Reasons for Failure of Antibiotics	Biofilm Function	Factors	Bacteria	Inactivated Antibiotics	Ref.
Hampered antibiotic penetration	Anti-spread barrier	EPS	P. aeruginosa (exopolysaccharides)	Cationic antibiotics aminoglycosides	[26,27]
Presence of antibiotic-degrading enzymes	To provide β-lactamases (β-LS)	↑ β-LS	K. pneumoniae	Ampicillin	[28]
			P. aeruginosa	Imipenem Ceftazidime	[29]
Increased biofilm resistance	To provide eDNA	↑ eDNA ↓ Mg2+	P. aeruginosa (Spermidine) Salmonella enterica	Cationic Peptides Aminoglycosides	[30,31,32]
Presence of persistent cells	To cause gradients in nutrients and oxygen concentration To promote differentiation in cell growth	Endogenous stress TA 1-systems	P. aeruginosa E. coli	Rifampicin Aminoglycosides	[33]
Presence of dormant cells		↓ Functions ↓ Energy ↓ Biosynthesis	E. coli	Fluoroquinolones	[34]
↑ Resistance to stress	To cause adaptive stress responses by heterogeneity	Changes in component/processes target of antibiotics	P. aeruginosa	Ofloxacin Gentamicin Meropenem Colistin	[35]
			E. coli K-12	Ofloxacin	[36]
↑ Exporting membrane proteins	To up-regulate the production of some efflux pumps	↑ Efflux pumps QS	E. coli Enterobacter aerogenes K. pneumonia	Multi-drugs	[37]
			P. aeruginosa	Azithromycin	[38]
Genetic diversity	To act as reservoir of genetic diversity by promoting plasmids transfer	Horizontal gene transfer (HGT) eDNA QS	P. aeruginosa	Aminoglycosides	[39]

¹ TA = toxin/antitoxin; ↑ = improved, higher, increased; ↓ = reduced, decreased.