Penicillins

Classes of PCN:

    • Natural PCN - PCN G, PCN V

    • Penicillinase resistant - methicillin, naficillin, dicloxacillin, oxacillin.

    • Aminopenicillins - ampicillin, amoxicillin

    • Antipseudomonal PCNs - piperacillin, mezlocillin, ticarcillin

PCNs irreversibly bind to PCN-binding proteins in the bacterial cell wall, causing osmotic rupture and death. Acquired resistance to these agents have diminished their role. Many bacterial species have altered PCN-binding proteins or expression of hydrolytic enzymes.

PCN remains among the drugs of choice for syphilis, group A streptococci, Listeria monocytogenes,Pasteurella multocida, Actinomyces, and some anaerobic infections.

Tx:

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

    • Procaine PCN G is an IM repository form of PCN G used as an alternative tx for neurosyphilis at a dose of 2.4 million units IM qd in combination with probenecid, 500 mg PO qid x 10-14 days.

    • Benzathine PCN is a long-acting IM repository form of PCN G commonly used to treat early latent syphilis (<1 yr duration) dose, 2.4 million units IM x 1, and late latent syphilis (>1 yr duration), dose, 2.4 million units IM qwk x 3 doses. It is occasionally given for group A streptococcal pharyngitis and prophylaxis after acute rheumatic fever.

    • PCN V, 250-500 mg PO q6h in oral PCN typically used for group A streptococcal pharyngitis.

    • Ampicillin 1-3 g IV q4-6h is drug of choice for treatment of infections caused by susceptible enterococcus spp, or L. monocytogenes. Ampicillin 250-500 mg PO q6h may be used for uncomplicated sinusitis, pharyngitis, otitis media, and UTI, but amoxicillin is generally preferred.

    • Ampicllin/sulbactam (Unasyn), 1.5-3 g IV q6h combines ampicillin wiht beta-lactamase inhibitor sulbactam, extending its spectrum to include MSSA, anaerobes, and many Enterobacteriaceae. The sulbactam component has a unique activity against some strains of Acinetobacter. Effective in URI and lower reps tract inf, UTI, abdominal, pelvic, and polymicrobial soft tissue infections, including those due to human or animal bites.

    • Amoxicillin, 250-1000 mg PO q8h or 775 mg extended-release q24h is a PO ABx similar to ampicillin commonly used for sinusitis, pharyngitis, otitis media, CAP, and UTIs.

    • Amoxicillin/clavulanic acid (Augmentin), 875 PO q12h, or 500 mg PO q8h, or 90 mg/kg/d divided q12h (Augmentin ES-600 susp), or 2 g PO q12h (Augmentin XR) is a PO ABx similar to ampicillin/sulbactam that combines amoxicillin with the beta-lactamase inhibitor clavulanate. It is used to treat complicated sinusitis and otitis media and for prophylaxis of human or animal bites after appropriate local treatment.

    • Naficillin and oxacillin, 1-2 g IV q4-6h are PCN-resistant synthetic PCNs that are the drug of choice for treating MSSA. Dose reduction should be considered in decompensated liver disease.

    • Dicloxacillin and cloxacillin, 250-500 mg PO q6h are PO ABx with a spectrum of activity similar to that of naficillin and oxacillin, which are typically used to treat localized skin infections.

    • Piperacillin, 3 g IV q4h or 4 g IV q6h is an extended-spectrum PCN with enhanced gram-negative activity as well as enterococcal activity. This agent has reasonable antipseudomonal activity but generally requires coadministration of an aminoglycosides for Tx of serious infections.

    • Ticarcillin/clavulanic acid (Timentin), 3.1 g IV q4-6h combines ticarcillin with the beta-lactamase inhibitor clavulanic acid. This combination extend the spectrum to include Enterobacteriaceae, MSSA, and anaerobes, making it useful for intraabdominal and complicated soft tissue infections. Also unique role in tx of Stenotrophomonas infections. This agent has a high sodium content and should be used cautiously in patients at risk for fluid overload.

    • Piperacillin/sulbactam (Zosyn), 3.375 g IV q6h or the higher dose of 4.5 g IV q6h for Pseudomonas combines piperacillin with the beta-lactamase inhibitor tazobactam. It has similar spectrum and indications as ticarcillin/clavulanic acid but enhanced activity against ampicillin-sensitive enterococci. The addition of an aminoglycoside should be considered for tx of serious infections caused by Pseudomonas aeruginosa or for nosocomial pneumonia.

Special Considerations:

All PCN derivatives have been rarely associated with anaphylaxis, interstitial nephritis, anemia, and leukopenia. Prolonged high-dose therapy (>2 weeks) is typically monitored with weekly Sr. Cr and CBC. LFTs are also monitored with oxacillin/naficillin as these agents can cause hepatitis. Ticarcillin/clavulanic acid can aggravate bleeding by interfering with platelets adenosine diphosphate receptors. All Pts should be asked about PCN, cephalosporin, or carbapenem allergy. These agents should not be used in a patient with reported serious PCN allergy without prior skin testing or desensitization, or both.