aztreonam (Rx)

>10%

Inhalation

• Cough (54%)
• Sore throat (12%)
• Wheezing (16%)
• Fever (13%)

Injection

• Pain at injection site (12%; children); (2%; adults)
• Increase in serum transaminases (4-6%)
• Neutropenia (3-11%, children); (<1%, adults)

1-10%

Inhalation

• Chest discomfort (8%)
• Abdominal pain (7%)
• Vomiting (6%)
• Bronchospasm (3%)
• Skin rash (2%)

Injection

• Rash (4%)
• Thrombocytopenia (4%, children); (<1% adults)
• Diarrhea (1%)
• Nausea (1%)
• Vomiting (1%)
• Fever (<1%)

< 1%

Inhalation

Facial edema

Joint swelling

Tightness in chest and throat

Bronchospasm

Skin rash

Injection

Abnormal taste

Anaphylaxis

Anemia

Angioedema

Aphthous ulcer

Breast tenderness

Bronchospasm

Clostridium difficile-associated diarrhea (CDAD)

Confusion

Diplopia

Dizziness

Dsypnea

Electrocardiographic changes (transient)

Erythema multiforme

Eosinophilia

Fever

Flushing

Halitosis

Headache

Hepatitis

Hypotension

Insomnia

Jaundice

Leukocytosis

Neutropenia

Pancytopenia

Seizures

Thrombocytopenia

Tinnitus

Tongue numbness

Toxic epidermal necrolysis

Urticaria

Vaginitis

Vertigo

Weakness

Wheezing

Postmarketing Reports

Encephalopathy

Contraindications

Hypersensitivity

Cautions

CDAD has been reported with use of nearly all antibacterial agents, including aztreonam

Dose reduction required with renal impairment

Coadministration with nephrotoxic drugs increases risk of renal impairment

Prolonged use may result in superinfection

Use caution in toxic epidermal necrolysis and renal impairment

Pregnancy category: B

Lactation: Drug is excreted in milk in low concentrations; use not recommended (American Academy of Pediatrics committee states that drug is compatible with nursing)

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Monobactam; inhibits cell wall synthesis by binding to penicillin binding proteins

Absorption

IM form well absorbed; IM/IV forms yield comparable serum concentrations

Peak plasma time: IM/IV push, ≤60 min; IV infusion, 1.5 hr

Distribution

Distributed widely to most body fluids and tissues; crosses placenta; enters breast milk

Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs); CSF level ~1% of blood level with normal meninges, 8-40% with inflamed meninges

Protein bound: 58%

Vd: Neonates, 0.26-0.36 L/kg; children, 0.2-0.29 L/kg; adults, 0.2 L/kg

Metabolism

Metabolized in liver

Elimination

Half-life: Adults with normal renal function, 1.7-2.9 hr; adults with end-stage renal disease, 6-8 hr

Excretion: Urine (60-70% as unchanged drug), feces (13-15%)

IV Incompatibilities

Additive: Metronidazole, nafcillin

Y-site: Acyclovir, alatrofloxacin, amphotericin B, amphotericin B cholesteryl sulfate, amsacrine, azithromycin, chlorpromazine, daunorubicin, ganciclovir, lorazepam, metronidazole, mitomycin, mitoxantrone, prochlorperazine, streptozocin, vancomycin(?; may depend on concentration)

IV Compatibilities

Additive (partial list): Ampicillin(?), cefazolin, cefoxitin(?), ciprofloxacin, linezolid, tobramycin, vancomycin (may be incompatible at high concentrations of both drugs)

Syringe: Clindamyin

Y-site (partial list): Allopurinol, amikacin, cephalosporins (most), cimetidine, ciprofloxacin, cisatracurium, diltiazem, diphenhydramine, dopamine, famotidine, fluconazole, furosemide, heparin, hydroxyzine, linezolid, magnesium sulfate, metoclopramide, morphine sulfate, ondansetron, propofol, sodium bicarbonate, trimethoprim-sulfamethoxazole, zidovudine

IV Preparation

Reconstituted solutions are colorless to light straw-yellow; may turn pink upon standing, without affecting potency

Use reconstituted solutions and IV solutions (in NS or D5W) within 48 hours if kept at room temperature or within 7 days if kept in refrigerator

IV/IM Administration

IM: Inject deep into large muscle mass

IV: Preferred for doses >1 g or in patients with severe life-threatening infections; administer drug by IV push over 3-5 minutes or by intermittent infusion over 20-60 minutes at final concentration not to exceed 20 mg/mL

Monitor infusion/injection sites carefully; administer around-the-clock to minimize variations in peak and trough serum levels