Penicillins

GENERAL PRINCIPLES

• Penicillins (PCNs) irreversibly bind PCN-binding proteins (PBPs) in the bacterial cell wall, ultimately causing osmotic rupture and death. Acquired resistance in many bacterial species through alterations in PBPs or expression of hydrolytic enzymes has limited their use.

• PCNs remain among the drugs of choice for syphilis and infections caused by PCN-sensitive streptococci and enterococci, methicillin-sensitive Staphylococcus aureus (MSSA), Listeria monocytogenes, Pasteurella multocida, and Actinomyces.

TREATMENT

• Aqueous PCN G (2-5 million units IV q4h or 12-30 million units daily by continuous infusion) is an IV preparation of PCN G and the drug of choice for most PCN-susceptible streptococcal infections and neurosyphilis.

• Procaine PCN G is an IM repository form of PCN G that can be used as an alternative treatment for neurosyphilis at a dose of 2.4 million units IM daily in combination with probenecid 500 mg PO qid for 10-14 days.

• Benzathine PCN is a long-acting IM repository form of PCN G that is used for treating early latent syphilis (1 y [2.4 million units IM weekly for three doses]). It is occasionally given for group A streptococcal pharyngitis and prophylaxis after acute rheumatic fever.

• PCN V (250-500 mg PO q6h) is an oral formulation of PCN that is typically used to treat group A streptococcal pharyngitis.

• Ampicillin (1-3 g IV q4-6h) is the drug of choice for treatment of infections caused by susceptible Enterococcus species or L. monocytogenes. Oral ampicillin (250-500 mg PO q6h) may be used for uncomplicated sinusitis, pharyngitis, otitis media, and urinary tract infections (UTIs), but oral amoxicillin is generally preferred.

• Ampicillin-Sulbactam (1.5-3.0 g IV q6h) combines ampicillin with the β-lactamase inhibitor sulbactam in a 2:1 ratio, thereby extending the spectrum to include MSSA, anaerobes, and many Enterobacterales.

• Amoxicillin (250-1000 mg PO q8h, 875 mg PO q12h, or 775 mg extended-release q24h) is an oral antibiotic similar to ampicillin that is used for uncomplicated sinusitis, pharyngitis, otitis media, community-acquired pneumonia (CAP), and UTIs.

• Amoxicillin-clavulanic acid (875 mg PO q12h, 500 mg PO q8h, 90 mg/kg/d divided q12h [Augmentin ES-600 suspension], or 2000 mg PO q12h [Augmentin XR]) is an oral antibiotic similar to ampicillin/sulbactam that combines amoxicillin with the β-lactamase inhibitor cl avul anate. It is useful for treating complicated sinusitis and otitis media and for prophylaxis of human or animal bites after appropriate local treatment.

• Nafcillin, oxacillin (1-2 g IV q4-6h), and dicloxacillin (250-500 mg PO q6h) are penicillinase­resistant synthetic PCNs that are drugs of choice for treating MSSA infections. Dose reduction of nafcillin should be considered in concomitant hepatic and renal impairment.

• Piperacillin-tazobactam (3.375 g IV q6h or 4.5 g IV q6h for Pseudomonas) combines piperacillin with the β-lactamase inhibitor tazobactam. This combination is active against most Enterobacterales, Pseudomonas, MSSA, ampicillin-sensitive enterococci, and anaerobes, making it useful for intra­abdominal and complicated polymicrobial soft tissue infections. Combination with vancomycin IV can increase risk of nephrotoxicity.

SPECIAL CONSIDERATIONS

Adverse events: All PCN derivatives have been associated with anaphylaxis, interstitial nephritis, elevated liver function tests (LFTs), anemia, leukopenia, thrombocytopenia, and phlebitis. Prolonged high-dose therapy (>2 wk) is typically monitored with weekly serum creatinine and complete blood count (CBC). Monitoring LFTs is especially important with oxacillin/nafcillin, as these agents can cause hepatitis. All patients should be asked about PCN, cephalosporin, or carbapenem allergies. These agents should not be used in patients with a reported serious PCN allergy without prior skin testing, desensitization, or both.