Treatment failures in invasive pneumococcal disease have been reported for macrolides, less-active fluoroquinolones (levofloxacin, ofloxacin, and ciprofloxacin), and some β-lactams (cefazolin, cefuroxime, ceftazidime, and ticarcillin).6
There have been no reports of bacteriological failure with penicillins active against resistant strains (high-dose penicillin, ampicillin/amoxicillin, and ceftriaxone or cefotaxime).6
Resistance to penicillin is caused by alterations in the penicillin-binding protein, and can be overcome by using higher doses of more active agents. Less-active cephalosporins have been associated with resistance more than aminopenicillins.19–
Pallares et al20
reported effectiveness of ceftriaxone, 1 g/d, or cefotaxime, 1.5 g q8h, in the treatment of invasive pneumococcal disease (26% with MICs > 0.5 μg/mL) in 185 adults. Among 522 episodes of nonmeningeal pneumococcal disease in a region plagued by pneumococcal resistance, no isolate could be found with a MIC to ceftriaxone/cefotaxime ≥ 4 μg/mL. These data support ceftriaxone, cefotaxime, or high-dose ampicillin/amoxicillin combined with a macrolide for empiric therapy of moderate-to-severe community-acquired pneumonia.