The prevalence of resistant isolates for beta-lactam antibiotics have been rapidly increasing in Streptococcus pneumoniae and Haemophilus influenzae. These strains having resistant elements are called penicillin-resistant S. pneumoniae(PRSP) and beta-lactamase-negative ampicillin-resistant H. influenzae(BLNAR). The mechanism of resistance was identified as the reduction of penicillin-binding proteins(PBPs) affinities as the target of beta-lactams. In PRSP, pbp1a, pbp2x, and pbp2b encoding PBP1A, -2X, and -2B enzymes, respectively, were altered. In contrast, mutations in the ftsI gene encoding PBP3A were only clarified in BLNAR. Characteristics of the resistance caused by PBPs alterations are a low-level resistance that decrease bactericidal action.