An isoxazolyl penicillin such as dicloxacillin, 0.25–0.5 g orally every 4–6 hours (15–25 mg/kg/d for children), is suitable for treatment of mild to moderate localized staphylococcal infections. These drugs are relatively acid-stable and have reasonable bioavailability. However, food interferes with absorption, and the drugs should be administered 1 hour before or after meals.
Methicillin, the first antistaphylococcal penicillin to be developed, is no longer used clinically due to high rates of adverse effects. Oxacillin and nafcillin, 8–12 g/d, given by intermittent intravenous infusion of 1–2 g every 4–6 hours (50–200 mg/kg/d for children), are considered drugs of choice for serious staphylococcal infections such as endocarditis.
C. Extended-Spectrum Penicillins (Aminopenicillins, Carboxypenicillins, and Ureidopenicillins)
These drugs have greater activity than penicillin against Gram-negative bacteria because of their enhanced ability to penetrate the Gram-negative outer membrane. Like penicillin G, they are inactivated by many β-lactamases.
The aminopenicillins, ampicillin and amoxicillin, have very similar spectrums of activity, but amoxicillin is better absorbed orally. Amoxicillin, 250–500 mg three times daily, is equivalent to the same amount of ampicillin given four times daily. Amoxicillin is given orally to treat bacterial sinusitis, otitis, and lower respiratory tract infections. Ampicillin and amoxicillin are the most active of the oral β-lactam antibiotics against pneumococci with elevated MICs to penicillin and are the preferred β-lactam antibiotics for treating infections suspected to be caused by these strains. Ampicillin (but not amoxicillin) is effective for shigellosis. Ampicillin, at dosages of 4–12 g/d intravenously, is useful for treating serious infections caused by susceptible organisms, including anaerobes, enterococci, L monocytogenes, and β-lactamase-negative strains of Gram-negative cocci and bacilli such as E coli, and Salmonella sp. Non-β-lactamase-producing strains of H influenzae are generally susceptible, but strains that are resistant because of altered PBPs are emerging. Due to production of β-lactamases by Gram-negative bacilli, ampicillin can no longer be used for empirical therapy of urinary tract infections and typhoid fever. Ampicillin is not active against Klebsiella sp, Enterobacter sp, P aeruginosa, Citrobacter sp, Serratia marcescens, indole-positive Proteus species, and other Gram-negative aerobes that are commonly encountered in hospital-acquired infections. These organisms intrinsically produce β-lactamases that inactivate ampicillin.