Mezlocillin

Antibiotic Class:

Penicillin (ureidopenicillin)

Antimicrobial Spectrum:

Gram-positive:  Streptococcus spp., Enterococcus, Listeria monocytogenes

Gram-negative:  H. influenzae, E. coli, Proteus mirabilis, Salmonella spp., Shigella 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. 

Pharmacodynamics:

Penicillins produce time-dependent killing

Pharmacokinetics:

Cmax: 263mcg/ml; Half-life: 0.8 hours; Table 6

Adverse Effects:

Hematologic:  anemia, thrombocytopenia, neutropenia, agranulocytosis

CNS:  seizures, dizziness

Endocrine:  hypokalemia

Renal:  nephrotoxicity, interstitial nephritis

Hepatic:  transient increases in transaminases

Other:  Jarisch-Herxheimer Reaction (fever, chills, sweating, tachycardia, hyperventilation, flushing, and myalgia)

Dosage:

Adult: 3-4g IV q4-6h

Pediatric:   < 1 week: 75 mg/kg  q12h

³ 1 week and < 1 month: 75 mg/kg q6-8 hrs

³ 1 month and < 12 yrs: 50-75 mg/kg q4h

³ 12 years: usual adult dose

Disease state based dosing:

Renal failure:  CrCL 10-50 mL/min: 1.5-3g q6-8h

CrCL < 10 mL/min: 1.5-2g q8h

Supplement after Hemodialysis: 3-4g

Contraindications/Warnings/Precautions:

Contraindications:  Anaphylaxis to mezlocillin or other penicillins

Precautions: 

• Cephalosporin hypersensitivity
• Patients with mononucleosis are more likely to develop a skin rash
• Coagulation abnormalities (bleeding time, platelet disorders)
• Electrolyte/fluid status (1.85 mEq sodium per gram or Hypokalemia)
• Prolonged neuromuscular blockade if used with vecuronium-type agents

Drug Interactions:

Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine

Methotrexate – increased methotrexate toxicity

Probenecid - increased mezlocillin levels

Pregnancy:

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

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, signs and symptoms of infection

Toxic:  Periodic CBC, urinalysis, BUN, SCr, AST and ALT, diarrhea, skin rash

Brand names/Manufacturer:

         BAYPEN (Bayer  - ITALY, GERMANY, AUSTRIA, FRANCE, ISRAEL)

         BAYPEN (Bayer - SPAIN)

         MELOCIN (Curasan - GERMANY)

         MEZLIN (Bayer - USA)

         OPTOCILLIN (Bayer – AUSTRIA, GERMANY)