Aztreonam

Antibiotic Class

Monobactam (monocyclic bacterially derived beta-lactam)

Antimicrobial Spectrum

Gram-negative bacteria:  Pseudomonas aeruginosa, Enterobacteriaceae, Escherichia coli, Haemophilus spp., Proteus mirabilis, Proteus spp., Providencia spp., Salmonella spp., Serratia spp., Shigella spp., and Klebsiella spp.

Mechanism of Action

Interferes with bactericidal cell wall synthesis by binding to and inactivating penicillin-binding-proteins. This binding causes the formation of elongation or bacterial filamentation resulting in cell lysis and cell death.

Pharmacodynamics

Aztreonam produces time-dependent killing.

Pharmacokinetics

Cmax: 255mg/L (after 2g IV dose); Half-life: 1.7 to 2 hours; Protein binding: 56 to 72%; Volume of distribution: 0.06 L/kg

Adverse Effects

Dermatologic: rash (rare)

Gastrointestinal: nausea, vomiting, diarrhea, pseudomembranous colitis (rare), increased liver enzymes, pancytopenia and neutropenia

Dermatologic: painful, injection-site reactions

Dosage

IV: 500mg, 1gram, 2gram vials for injection

Adult dose: IV/IM: 1-2 g q8h

Systemic or life-threatening infections: 2 g IV/IM q6h

Severe systemic infections: 2g IV q6-8h, maximum of 8g per day

Urinary tract infection: 0.5-1g IV/IM q8-12h

Pediatric dose:

Infants less than 1 week of age:             30 mg/kg q12h

Infants 1 to 4 weeks of age:                  30 mg/kg q8h

Infants greater than 1 month of age:       30 mg/kg q6-8h

Disease state based dosing

Renal failure:     CrCl 10-30 mL/min:  Normal loading dose, followed by a 50% reduction of the loading dose given at the same frequency of normal patients

CrCl less than 10 mL/min:  Normal loading dose, followed by a 75% reduction of the loading dose given at the same frequency of normal patients

Hepatic failure:  No dosing changes recommended at this time.

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 1-2g IV q12h

CVVHD (Continuous venovenous hemodialysis): 2g IV q12h

CVVHDF (Continuous venovenous hemodiafiltration) 2g IV q12h

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: extremely low birth-weight infants or infants with congenital/acquired arginase deficiency; use aztreonam arginate with caution

Warnings: Although cross-reactivity with penicillins and cephalosporins is exceedingly rare, ceftazidime and aztreonam share a common side-chain. For this reason, use caution in administering aztreonam in patients who endorse a ceftazidime allergy.

Drug Interactions

No clinically significant drug interactions have been identified.

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 (e.g. fever, WBC)

Brand names/Manufacturer