penicillin

Introduction

In general, low toxicity. Most common agents along with cephalosporins implicated in drug allergies.

Indications

• oral: mild to moderately severe penicillin-sensitive infections
• parenteral: severe penicillin-sensitive infections or when GI tract is not an acceptable route of administration
• treatment of sensitive gonorrhea
• treatment of choice for syphilis

Dosage

• oral (Pen VK) 250-500 mg every 6 hours
• benzathine (IM) 600,000- 2,400,000 units IM weekly
• procaine (IM) 600,000- 2,400,000 units IM QD

Dosage adjustment in renal failure

(Pen G)

creatinine clearance	dosage*
> 30 mL/min	1-2 x 10E6 units IV every 4 hours
10-30 mL/min	1-2 x 10E6 units IV every 6 hours
< 10 mL/min	1-2 x 10E6 units IV every 12 hours
post-dialysis	2 x 10E6 units

* higher doses (3-4 x 10E6 units) should be considered for streptococcal endocarditis or pneumococcal meningitis

Pharmacokinetics

• penicillin V (oral)
  • 60% absorbed
  • food reduces or delays absorption
  • should be taken on an empty stomach
• benzathine (IM) & procaine (IM) penicillin
  • slow depot absorption
• widely distributed in body fluids, tissues & cavities
• poor CSF penetration (doses of > 20 x 10E6 units/day used to treat meningitis)
• 60-70% eliminated in the urine
• minimal hepatic metabolism with excretion in the bile
• penicillin G is removed by hemodialysis
• elimination 1/2life
  • normally 30-40 minutes
  • up to 7-10 hours in patients with renal failure
  • up to 7-10 hours in patients with renal & hepatic failure

Antimicrobial activity

• mostly gram positive bacteria
• some gram negative coverage
• some anaerobic coverage

Antibiotic resistance

• beta-lactamase production
  • penicillin-resistant Staphylococcus
  • Haemophilus
  • anaerobes
  • aerobic gram-negative bacteria
• alterations in penicillin-binding proteins
  • methicillin-resistant Staphylococcus aureus (MRSA)
  • Streptococci
  • Neisseria
  • Enterococci

Adverse effects

• hypersensitivity
  • IgE-mediated
  • anaphylaxis may occur
  • desensitization is hazardous
• electrolyte disturbances
  • hypernatremia
  • hyperkalemia
  • hyperchloremic alkalosis
• dose-related neurotoxicity
• nausea/vomiting
• rashes
• serum sickness reactions
• confusion
• drowsiness
• lethargy
• seizures (high dose)
• phlebitis

Drug interactions

• probenecid produces higher concentrations & longer 1//2life of penicillin
• aminoglycosides are synergistic with penicillin
  • should not be given in same IV solution or syringe due to drug inactivation

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Laboratory

• penicillin in specimen
  • penicillin in serum/plasma
  • penicillin in urine

Mechanism of action

inhibition of bacterial cell wall synthesis

More general terms

• penicillanate
• beta-lactam antibiotic

More specific terms

• 1st generation penicillin (natural)
• 2nd generation penicillin (penicillinase-resistant)
• 3rd generation penicillin (aminopenicillin)
• 4th generation penicillin (extended-spectrum)
• penicillin V (Pen-Vee K, Veetids, V-Cillin K, Aoracillin-B, Beepen VK, Lanacillin VK, Ledercillin VK, Robicillin VK, Wincillin-VK)
• temocillin (Temopen)

Additional terms

• penicillin binding protein
• type B drug reaction; drug-induced hypersensitivity syndrome; drug rash with eosinophilia & systemic symptoms (DIHS, DRESS)

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?