Haemophilus influenzae has become increasingly resistant to beta-lactam antibiotics. Three major mechanisms, both enzymatic and non-enzymatic, are involved. Enzymatic resistance is mainly due to production of a TEM-1 plasmid-mediated beta-lactamase, and in some cases to a new enzyme ROB-1. Of the non-enzymatic mechanisms, decreased permeability due to alteration of outer membrane proteins seems to be rare in comparison to decreased affinity of penicillin-binding proteins for beta-lactam antibiotics. Enzymatic resistance is present in about 10-20% of clinical isolates, while non-enzymatic resistance is present only in 2-4%.