Azlocillin

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

Distribution:  Total protein binding: 30 to 40%;

Distribution sites:  aqueous humor, bile, bone, CSF, lungs, urine

Volume of distribution:  14 L

Excretion:  Renal excretion: 60 to 75%; elimination half-life: 1.53 hours

Adverse Effects

Hematologic:  anemia, thrombocytopenia, neutropenia, agranulocytosis

Endocrine:  hyperthermia

Renal:  nephrotoxicity, interstitial nephritis

Hepatic:  transient increases in transaminases

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

Dosage

Gram-negative infections:  2 to 5 grams every 8 hours IV

Serious infections:  225 to 300 mg/kg/day IV in 4 to 6 divided doses (usual IV doses 3g q4h or 4g q6h) (up to 18 g/day)

Disease state based dosing

Renal failure: CrCl 30 to 50 mL/min:  increase dosing interval to every 4 to 6 hours

                       CrCl between 10 to 30 mL/min:  2 g IV q8h

                       CrCl < 10 mL/min:  3 g IV q12h           

Hepatic failure:  No dosing changes recommended at this time.

Contraindications/Warnings/Precautions

Contraindications:  Anaphylaxis to azlocillin or other penicillins

Precautions: 

• Cephalosporin hypersensitivity
• Patients with mononucleosis are more likely to develop a skin rash
• Patients with restricted salt intake; each gram of azlocillin contains 2.17 mEq of sodium
• Renal insufficiency

Drug Interactions

Ciprofloxacin – decreased clearance of ciprofloxacin

Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine

Probenecid - increased azlocillin 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

Azlin (Miles -United States)

Securopen (Bayer – Italy, UK, France, Spain, Austria, Ireland, Norway, Germany, Australia)