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Penicillins (penicillin G/V, amoxicillin, ampicillin, piperacillin)

Beta-lactam antibiotic — penicillin class

Mechanism of action

Bind penicillin-binding proteins (PBPs) on bacterial cell walls and inhibit transpeptidation, blocking peptidoglycan cross-linking. Result: cell-wall lysis and bactericidal killing of susceptible organisms. Coverage varies by sub-class — narrow-spectrum (penicillin G/V) for streptococci and syphilis; aminopenicillins (amoxicillin, ampicillin) for some gram-negatives; antipseudomonal (piperacillin) for broader coverage including Pseudomonas.

Adverse effects

Life-threatening / NCLEX-tested

  • Anaphylaxis — life-threatening; 5–10% of US patients report a penicillin allergy but most are not true IgE-mediated; clarify history carefully
  • Stevens-Johnson syndrome / toxic epidermal necrolysis (rare)
  • Severe diarrhea / Clostridioides difficile colitis
  • Acute interstitial nephritis (more with methicillin/nafcillin)
  • Hemolytic anemia with high-dose IV penicillin G
  • Seizures with very high doses, especially in renal impairment
  • Severe hyperkalemia with potassium-penicillin (large IV doses)

Side effects

Common — what to teach

  • Diarrhea (especially with amoxicillin)
  • Nausea
  • Maculopapular rash (often non-allergic, especially with amox + EBV/mononucleosis)
  • Yeast vaginitis or oral thrush
  • Mild abdominal cramps
  • Black hairy tongue (rare, harmless)

Food & drug interactions

Probenecid raises penicillin levels by blocking renal tubular secretion. Oral contraceptives may have reduced efficacy with antibiotics in general — counsel backup contraception during course. Methotrexate levels rise with penicillins — toxicity risk. Aminoglycosides synergize for serious gram-positive infections (give in separate lines — direct mixing inactivates aminoglycosides).

Nursing implications

Assessment, monitoring, patient teaching

  • ALLERGY ASSESSMENT: clarify the reaction (rash vs anaphylaxis), timing, and severity; "PCN allergy" without anaphylaxis often means cephalosporins are safe — discuss with the team
  • Always have epinephrine, diphenhydramine, and IV access available for first IV doses; observe for at least 30 minutes after first dose for anaphylaxis
  • Take oral penicillin V on an empty stomach for best absorption; amoxicillin can be taken with or without food
  • Complete the FULL prescribed course even if symptoms resolve — incomplete courses drive resistance
  • Counsel on diarrhea — bloody, severe, or persistent diarrhea = call (rule out C. diff)
  • For depot injections (benzathine penicillin G for syphilis): IM only, NEVER IV (cardiac arrest if given IV); use a large muscle, observe for 30 minutes
  • Reconcile renal function — many penicillins need renal dose adjustment

When to hold / contraindications

  • Documented IgE-mediated penicillin allergy (anaphylaxis, urticaria, angioedema)
  • Severe rash, fever, mucosal involvement (suspect SJS/TEN/DRESS)
  • Severe acute kidney injury (some require dose adjustment, others contraindicated)
  • Active C. difficile infection until provider review
  • Benzathine PCN G via IV route — never give IV

Memory anchor

Penicillins end in "-cillin." "30-minute observation, true allergy = STOP, depot = IM only." Amox + mono virus = nuisance rash, not anaphylaxis.

Reminder: Drug cards are study aids, not clinical guidance. Always cross-check doses, holds, and contraindications with your facility's formulary and your clinical instructors before patient care.

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