Penicillin (penicillinase-resistant penicillin)
Staphylococcus spp., Streptococcal spp.
Mechanism of Action:
Exerts bactericidal activity via inhibition of bacterial cell wall synthesis by binding one or more of the penicillin binding proteins (PBPs). Exerts bacterial autolytic effect by inhibition of certain PBPs related to the activation of a bacterial autolytic process.
Penicillins produce time-dependent killing
Cmax: 20mcg/ml; Half-life: 0.5-1 hours; Table 6
Hematologic: neutropenia, agranulocytosis, bone marrow depression
CNS: seizures, fever, pain
Renal: interstitial nephritis
Hepatic: transient increases in transaminases
Other: thrombophlebitis, tissue necrosis, Jarisch-Herxheimer Reaction (fever, chills, sweating, tachycardia, hyperventilation, flushing, and myalgia)
Disease state based dosing:
Renal failure: A 50% dose reduction may be appropriate in patients with renal and hepatic insufficiency.
Hepatic failure: A 50% dose reduction may be appropriate in patients with renal and hepatic insufficiency.
Dosing during Continuous Renal Replacement Therapy
CVVH (Continuous venovenous hemofiltration): 2g IV q4-6h
CVVHD (Continuous venovenous hemodialysis): 2 g IV q4-6h
CVVHDF (Continous venovenous hemodiafiltration): 2 g IV q4-6h
Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.
Contraindications: Anaphylaxis to nafcillin or other penicillins
Precautions: Cephalosporin hypersensitivity
Nafcillin is an inducer of the cytochrome P450 3A4 isoenzyme. Caution should be exercised and monitoring is suggested when concomitantly administering nafcillin with drugs that have narrow therapeutic windows and are substrates of the CYP3A4 enzyme.
Chloramphenicol – decreased nafcillin efficacy
Cyclosporine - decreased cyclosporine concentrations
Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine
Nifedipine - decreased nifedipine efficacy
Probenecid – increased nafcillin levels
Warfarin – decreased anticoagulant effectiveness
Category B: No evidence of risk in humans but studies inadequate.
Therapeutic: Culture and sensitivities, signs and symptoms of infection
Toxic: Periodic CBC, urinalysis, BUN, SCr, AST and ALT