Ampicillin/sulbactam

Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli

Mechanism of Action:

The beta-lactamase inhibitors are recognized as substrates for the beta-lactamases produced by bacteria. This allows the actual beta-lactams to attack the bacterial cell wall by binding to penicillin binding proteins

Pharmacodynamics:

Time dependent killer (Time > MIC)

Pharmacokinetics:

(of the sulbactam)

Dose 500mg: Cmax: 20-43 mcg/L; Protein binding: 38%; Volume of distribution: 0.16-0.5L/kg; Table 5

Adverse Effects:

No new adverse effects are seen as a result of adding beta-lactamase inhibitors to beta-lactam antibiotics. The adverse reactions would remain the same for the parent compound

Dosage:

IV: Complete listing on Table 6

Dosing in adults:

Mild/Moderate: 1.5g q6-8h

Severe: 3g q6h

Dosing in pediatrics:

Mild/Moderate: 150-300mg/kg/day divided q6h

Severe: 150-300mg/kg/day divided q6h

Table 8

Disease state based dosing:

Renal failure: CrCl > 30mL/min: 1.5-3g q6-8h

CrCl 15-29mL: 1.5-3g q8-12h

CrCl 5-14mL/min: 1.5-3g q12-24h

Hepatic failure: No dosing changes recommended at this time.

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 3g IV q12h

CVVHD (Continuous venovenous hemodialysis): 3g IV q8h

CVVHDF (Continuous venovenous hemodiafiltration) 3g IV q8h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Precautions: hypersensitivity to penicillins, history of gastrointestinal disease, particularly colitis, renal impairment

Drug Interactions:

Allopurinol – higher probablility of ampicillin rash; Atenolol – decreased atenolol effectiveness; Contraceptives - decreased contraceptive effectiveness; Lansoprazole – loss of ampicillin efficacy; Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine; Omeprazole – loss of ampicillin efficacy; Pantoprazole – loss of ampicillin efficacy; Probenecid - increased ampicillin levels; Rabeprazole – loss of ampicillin efficacy

Pregnancy:

Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements:

Therapeutic: Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count

Toxic: Urinalysis, BUN, SCr, AST and ALT, skin rash, Neutropenia and leukopenia,

Brand names/Manufacturer:

Unasyn/Pfizer pharmaceuticals