ampicillin (Principen, Omnipen, Amcill, Polycillin, Polycillin-N, D-cillin, J-cillin, Marcillin, Rancillin Totacillin-N)

Introduction

Tradenames: Principen, Omnipen. 3rd generation penicillin.

Indications

• infections caused by susceptible gram positive bacteria & gram negative bacteria, including
  • intra-abdominal infection
    • gastrointestinal infection
      • gastroenteritis, enterocolitis
    • cholangitis
    • acute otitis media,
    • endocarditis
    • upper respiratory tract infection
      • acute sinusitis
      • pharyngitis
      • epiglottitis
    • lower respiratory tract infection
      • pneumonia
    • urogenital infections
    • skin or soft tissue infections
• treatment of choice (generally in combination with gentamicin) for treatment of serious enterococcal infections
• treatment of meningitis caused by Listeria monocytogenes
• empiric treatment of fever of unknown origin
• prophylaxis for bacterial endocarditis
• prophylaxis for perioperative infection, including
  • gastrointestinal surgery
  • hysterectomy
  • cesarean section
• bacterial infections associated with necrosis

Dosage

• 1-2 g IV/IM every 4-6 hours.
• 250-500 mg PO QID.

Pediatrics: 50-200 mg/kg/day divided QID.

Tabs: 250 & 500 mg.

Elixir: 125 & 250 mg/5 mL.

Dosage adjustment in renal failure

Table

creatinine clearance	dose
> 30 mL/min	1-2 g every 4-6 hours
10-30 mL/min	1-2 g every 6 hours
< 10 mL/min*	1-2 g every 8 hours

* dose after hemodialysis

Pharmacokinetics

• CSF levels are 11-65% of serum levels with meningeal inflammation
• elimination 1/2life 1 hour (7-20 hours ESRD)

elimination via kidney

1/2life = 1-2 hours

elimination by hemodialysis = +

Antimicrobial activity

Gram positive:

• Streptococcus sp
• Enterococcus sp
• Listeria

Gram negative:

• Neisseria meningitidis
• Salmonella
• Shigella
• Proteus
• Campylobacter fetus
• Haemophilus
  • Haemophilus influenzae
  • Haemophilus parainfluenzae
• Yersinia pseudotuberculosis
• Escherichia coli

Anaerobes:

• Peptostreptococcus
• Clostridium species

Adverse effects

• common (> 10%)
  • rash
    • distingush non-allergic rash from hypersensitivity reaction
    • incidence higher in patients with viral infections (CMV, EBV)* Salmonella, lymphocytic leukemia (ALL)*, hyperuricemia, diarrhea, vomiting, oral candidiasis
    • duration of rash is independent of whether ampicillin is discontinued or not
    • no risk of allergic reaction on re-exposure to ampicillin after underlying condition has resolved
  • urticarial rash in infectious mononucleosis
• less common (1-10%)
  • severe abdominal or stomach cramps
  • diarrhea
• uncommon (< 1%)
  • blood dyscrasias (rare)
  • seizures (rare)

* maculopapular rash assoicated with use of intravenous ampicillin in patients with CMV, EBV, or ALL is not a drug allergy & the duration of the rash is independent of whether or not ampicillin is continued

Drug interactions

• coadministration of allopurinol increases the frequency of rash
• ampicillin decreases atenolol absorption
• probenecid increases 1/2life of ampicillin

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin
• drug interaction(s) of beta-adrenergic receptor antagonists with ampicillin

Mechanism of action

inhibition of bacterial cell wall synthesis

More general terms

• 3rd generation penicillin (aminopenicillin)

Additional terms

• Enterococcus
• Listeria

Component of

• ampicillin sulbactam (Unasyn)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6249
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2174
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=23565
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6248
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=447453
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2173