aztreonam
Azactam

Available forms
Available by prescription only
Injection: 500-mg, 1-g, 2-g vials

Indications and dosages
 Urinary tract, respiratory tract, intra-abdominal, gynecologic, or skin infections; septicemia caused by gram-negative bacteria; adjunct therapy in pelvic inflammatory disease ◇; gonorrhea ◇. Adults: 500 mg to 2 g I.V. or I.M. q 8 to 12 hours. For severe systemic or life-threatening infections, 2 g q 6 to 8 hours may be given. Maximum dose is 8 g daily. For gonorrhea, give 1 g I.M. single dose.
≡ Dosage adjustment. For patients with a creatinine clearance of 10 to 30 ml/minute, reduce dose by one-half after an initial dose of 1 to 2 g. If creatinine clearance is below 10 ml/minute, an initial dose of 500 mg to 2 g should be followed by one-fourth of the usual dose at the usual intervals; give one-eighth the initial dose after each hemodialysis session.

Pharmacodynamics
Antibacterial action: Aztreonam is a monobactam that inhibits mucopeptide synthesis of the bacterial cell wall. It preferentially binds to penicillin-binding protein 3 (PBP3) of susceptible organisms and often causes cell lysis and cell death.
 Aztreonam has a narrow spectrum of activity and is usually bactericidal in action. Aztreonam is effective against Escherichia coli, Enterobacter species, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. It has limited activity against Citrobacter species, Haemophilus influenzae, Klebsiella oxytoca, Hafnia species, Serratia marcescens, Enterobacter aerogenes, Morganella morganii, Providencia species, Moraxella catarrhalis,Proteus vulgaris, and Neisseria gonorrhoeae.

Pharmacokinetics
Absorption: Absorbed poorly from GI tract after oral administration but is absorbed rapidly and completely after I.M. administration.
Distribution: Distributed rapidly and widely to all body fluids and tissues, including bile, breast milk, and CSF. It crosses the placental barrier and is found in fetal circulation.
Metabolism: From 6% to 16% is metabolized to inactive metabolites by nonspecific hydrolysis of the beta-lactam ring; 56% to 60% is protein-bound, less if renal impairment is present.
Excretion: Excreted principally in urine as unchanged drug by glomerular filtration and tubular secretion; 1.25% to 3.25% is excreted in feces as unchanged drug. Half-life averages 11/2 hours. Drug appears in breast milk. It may be removed by hemodialysis and peritoneal dialysis.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal function and in elderly patients.

Interactions
Drug-drug. Aminoglycosides, beta-lactam antibiotics (including cefoperazone, cefotaxime, clindamycin, metronidazole, piperacillin): Cause synergistic or additive effects. Avoid use together.
Chloramphenicol: Causes antagonistic reaction. Give several hours apart.
Potent inducers of beta-lactamase production (cefoxitin, imipenem): May inactivate aztreonam. Avoid use together.
Probenecid: May prolong tubular secretion of aztreonam. Avoid use together.

Adverse reactions
CNS: seizures, headache, insomnia, confusion.
CV: hypotension.
GI: diarrhea, nausea, vomiting.
GU: renal impairment.
Hematologic: neutropenia, anemia, pancytopenia, thrombocytopenia, leukocytosis, thrombocytosis.
Hepatic: liver dysfunction.
Skin: discomfort and swelling at I.M. injection site, thrombophlebitis at I.V. site.
Other: hypersensitivity reactions (rash, anaphylaxis).

Effects on lab test results
• May increase BUN, creatinine, ALT, AST, and LDH levels.
• May increase PT, PTT, and INR. May decrease neutrophil, RBC, and WBC counts and hemoglobin. May increase or decrease platelet counts.

Overdose and treatment
No information is available on the symptoms of overdose. Hemodialysis or peritoneal dialysis increases elimination of aztreonam.

Special considerations
• Aztreonam therapy alters urinary glucose determinations using cupric sulfate (Clinitest or Benedict’s solution) and gives false-positive Coombs’ test results.
• Drug also has been used to treat bone and joint infection caused by susceptible aerobic, gram-negative bacteria.
• To reconstitute for I.M. use, dilute with at least 3 ml of sterile water for injection, bacteriostatic water for injection, normal saline solution, or bacteriostatic normal saline solution for each g of aztreonam (15-ml vial).
• To reconstitute for I.V. use, add 6 to 10 ml of sterile water for injection to each 15-ml vial; for I.V. infusion, prepare as for I.M. solution. May be further diluted by adding to normal saline solution, Ringer’s solution, lactated Ringer’s solution, D₅W, D₁₀W, or other electrolyte-containing solutions. For I.V. piggyback (100-ml bottles), add at least 50 ml of diluent for each g of aztreonam. Final concentration shouldn’t exceed 20 mg/ml.
• I.V. route is preferred for doses larger than 1 g or in patients with bacterial septicemia, localized parenchymal abscesses, peritonitis, or other life-threatening infections; administer by direct I.V. push over 3 to 5 minutes or by intermittent infusion over 20 to 60 minutes.
• Solutions may be colorless or light straw yellow. On standing, they may develop a slight pink tint; potency isn’t affected.
• Drug may be stored at room temperature for 48 hours or in refrigerator for 7 days.
• Monitor renal and hepatic function tests. Reduced dose may be required in patients with impaired renal function, cirrhosis, or other hepatic impairment.
• Test for Clostridium difficile in patients with prolonged diarrhea.
Pregnant patients
• There are no adequate controlled studies regarding use in pregnant women.
Breast-feeding patients
• Although drug appears in breast milk, it isn’t absorbed from infant’s GI tract and is unlikely to cause any serious problems.
Pediatric patients
• Manufacturer doesn’t recommend use of drug in infants younger than age 1 month.
Geriatric patients
• Studies have shown that the half-life of aztreonam may be prolonged in patient ages 65 to 75 because of diminished renal function.

Patient education
• Tell patient to call immediately if rash, redness, or itching develops.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use