aztreonam

Aztreonam is an antibiotic used to treat infections caused by a wide spectrum of susceptible aerobic gram-negative bacteria. Gram-negative bacteria have an additional membrane outside the cell wall that gram-positive bacteria lack, and the two types are identified by the Gram stain lab test. Aerobic bacteria require oxygen to survive while anaerobic bacteria thrive in the absence of oxygen. Aztreonam kills (bactericidal) gram-negative aerobic bacteria, but has no activity against gram-positive and anaerobic bacteria.

Aztreonam is a synthetic monocyclic beta-lactam (monobactam) antibiotic. Beta-lactam antibiotics contain a beta-lactam ring in their chemical structure, a compound that binds to penicillin-binding proteins, enzymes that are essential for the synthesis of peptidoglycan, a vital component of bacterial cell wall. Aztreonam blocks the synthesis of peptidoglycan that provides stability to the cell wall and destroys the integrity of the cell wall structure, causing leakage of the bacterial cell contents and death.

Bacteria develop resistance to beta-lactam antibiotics by producing beta-lactamases, enzymes that cleave the beta-lactam rings in the antibiotics and degrade them. Aztreonam is structurally different from other beta-lactam antibiotics such as penicillins and cephalosporins. Its unique molecular structure makes it resistant to degradation by beta-lactamases, making it a potent agent against organisms that develop resistance to other antibiotics.

Aztreonam may be administered as an intravenous or intramuscular injections to treat systemic infections and is inhaled in the treatment of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis, an inherited disorder that causes the body fluids to be excessively thick and sticky, damaging the lungs, digestive tract and other organs.

The uses of aztreonam include treatment of the following:

FDA-approved:

• Urinary tract infections
• Lower respiratory tract infections
• Septicemia
• Skin and skin structure infections
• Intra-abdominal infections
• Gynecological infections
• Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (inhaled)

Off-label uses

• Bacterial meningitis
• Native vertebral osteomyelitis
• Stenotrophomonas maltophilia infection
• Perioperative surgical prophylaxis

Susceptible aerobic gram-negative organisms include:

• Citrobacter species
• Enterobacter species
• Escherichia coli
• Haemophilus influenzae (including ampicillin-resistant and other penicillinase-producing strains)
• Klebsiella oxytoca
• Klebsiella pneumoniae
• Proteus mirabilis
• Pseudomonas aeruginosa
• Serratia species

• Do not use aztreonam in patients with known hypersensitivity to any component of the formulation.
• Aztreonam may cause hypersensitivity reactions in patients with or without prior exposure to the drug. If a patient develops allergic reaction, discontinue aztreonam, institute appropriate supportive treatment and monitor until symptoms resolve.
• Although studies suggest that aztreonam is rarely cross-reactive, prescribe and administer aztreonam with caution in patients who have had a history of hypersensitive reactions to other beta-lactam antibiotics including penicillins, cephalosporins or carbapenems.

Warnings specific to aztreonam injections:

• In the absence of a proven or strongly suspected bacterial infection or a prophylactic indication of susceptible organism, aztreonam is unlikely to be beneficial and increases the risk of development of drug-resistant bacteria.
• As with most antibacterial agents, aztreonam treatment can alter the gut flora and lead to Clostridium difficile overgrowth and C. difficile associated diarrhea (CDAD), even up to two months after discontinuation. Monitor patients for signs of CDAD, and if confirmed, treat C. difficile infection promptly, stop all antibiotics not directed against C. difficile.
• There have been rare reports of toxic epidermal necrolysis (TEN) associated with aztreonam treatment in patients undergoing bone marrow transplant with multiple risk factors, including sepsis, radiation therapy and concurrent administration of other drugs associated with TEN.
• Closely monitor patients with impaired liver or kidney function during treatment with aztreonam.
• If aminoglycoside antibiotics are concurrently used with aztreonam, monitor kidney function, especially if high doses and prolonged treatment with aminoglycosides are required because of their potential for nephrotoxicity and ototoxicity.
• Prolonged use of aztreonam can cause overgrowth of non-susceptible organisms and result in fungal or bacterial superinfections, which should be treated promptly.

Warnings specific to aztreonam inhalation:

• Inhaled aztreonam can cause bronchospasms. Stop treatment if chest tightness develops during inhalation.
• In the absence of known Pseudomonas aeruginosa infection in patients with cystic fibrosis, aztreonam treatment is unlikely to be beneficial and increases the risk of development of drug-resistant bacteria.

Aztreonam injection

Common side effects of aztreonam injection include:

• Administration site reactions including:
  • Pain and discomfort
  • Swelling
  • Redness (erythema)
  • Tissue hardening (induration)
  • Vein inflammation (phlebitis)
  • Phlebitis with blood clot (thrombophlebitis)
• Nausea
• Vomiting
• Diarrhea
• Rash
• Low count of neutrophil immune cells (neutropenia)
• Increase in eosinophil immune cells
• Increase in platelet count
• Increase in blood clotting (prothrombin) time
• Increase in liver enzymes ALT and AST
• Increase in alkaline phosphatase
• Increase in serum creatinine

Less common side effects of aztreonam injection include:

• Abdominal cramps
• C. difficile-associated diarrhea
• Colon inflammation (pseudomembranous colitis)
• Gastrointestinal bleeding
• Liver inflammation (hepatitis)
• Jaundice
• Flushing
• Transient ECG changes
• Low blood pressure (hypotension)
• Chest pain
• Wheezing
• Shortness of breath (dyspnea)
• Muscle aches
• Weakness
• Headache
• Feeling ill (malaise)
• Blood disorders including:
  • Low red blood cell count (anemia)
  • Low platelet count (thrombocytopenia)
  • Low count of all types of blood cells (pancytopenia)
  • High count of leukocyte immune cells (leukocytosis)
• Skin reactions including:
  • Hives (urticaria)
  • Red or purple spots from bleeding beneath the skin (purpura/petechiae)
  • Itching (pruritus)
  • Excessive sweating (diaphoresis)
  • Erythema multiforme
  • Exfoliative dermatitis
  • Toxic epidermal necrolysis
• Hypersensitivity reactions including:
  • Bronchospasm
  • Swelling beneath the skin and mucous membrane (angioedema)
  • Severe allergic reaction (anaphylaxis)
• Confusion
• Insomnia
• Dizziness
• Vertigo
• Abnormal skin sensation (paresthesia)
• Brain damage (encephalopathy)
• Seizure
• Ringing in the ears (tinnitus)
• Double vision (diplopia)
• Altered taste
• Numb tongue
• Mouth ulcer
• Bad breath (halitosis)
• Nasal congestion
• Sneezing
• Breast tenderness
• Vaginal Candida yeast infection (candidiasis)
• Vaginal inflammation (vaginitis)

Inhaled aztreonam inhalation

Common side effects of inhaled aztreonam include:

• Cough
• Nasal congestion
• Wheezing
• Throat and voice box pain (pharyngolaryngeal pain)
• Fever (pyrexia)
• Chest discomfort
• Abdominal pain
• Vomiting
• Bronchospasm
• Rash

Less common side effects of inhaled aztreonam include:

• Joint swelling
• Joint pain (arthralgia)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Powder for injection (Azactam)

• 1 g
• 2 g

Solution, inhalation (Cayston)

• 75 mg/single-use vial

Adult:

Systemic Infections

• Moderately severe: 1-2 g intravenous/intramuscular (IV/IM) once every 8-12 hours; not to exceed 8 g/day
• Severe or life-threatening: 2 g IV/IM once every 6-8 hours; not to exceed 8 g/day

Pseudomonal Infections

• 2 g IV/IM once every 6-8 hours; not to exceed 8 g/day

Urinary Tract Infections

• 0.5-1 g IV/IM once 8-12 hours; not to exceed 8 g/day

Dosing Modifications

Renal impairment

• Creatinine clearance (CrCl) 10-30 mL/minute: 1-2 g loading dose, then 50% of usual dosage
• CrCl below 10 mL/minute: 1-2 g loading dose, then 25% of usual dosage

Cystic Fibrosis (CF)

Cayston

• Indicated to improve respiratory symptoms in patients with CF infected with Pseudomonas aeruginosa
• 75 mg inhaled once every 8 hours for 28 days; use only with Alterna nebulizer; do not repeat for 28 days after completion
• Doses should be administered at least 4 hours apart
• Use bronchodilator before administration; administer short-acting beta agonists 15 minutes to 4 hours before or long-acting beta agonists 30 minutes to 12 hours before
• If taking mucolytics, take after bronchodilators, but before aztreonam

Reconstitution and Storage

• Store vials and diluent refrigerated at 2-8 degrees C (36-46 degrees F)
• Once removed from refrigerator, may store at room temperature (up to 25 degree C; 77 degrees F) for up to 28 days
• Use immediately upon reconstitution; do not reconstitute more than 1 dose at a time

Pediatric:

Mild-to-Moderate Infections

• Children below 9 months: Safety and efficacy not established
• Children above 9 months: 30 mg/kg IV once every 8 hours; not to exceed 120 mg/kg/day  

Moderate-to-Severe Infections

• Children below 9 months: Safety and efficacy not established
• Children above 9 months: 30 mg/kg IV once every 6-8 hours; not to exceed 120 mg/kg/day

Cystic Fibrosis (CF)

Cayston

• Indicated to improve respiratory symptoms in patients with CF infected with Pseudomonas aeruginosa
• Children below 7 years: Safety/efficacy not established
• Children above 7 years: As adults, 75 mg inhaled once every 8 hours for 28 days; use only with Alterna nebulizer; do not repeat for 28 days after completion
• Doses should be administered at least 4 hours apart
• Use bronchodilator before administration; administer short-acting beta agonists 15 minutes to 4 hours before or long-acting beta agonists 30 minutes to 12 hours before
• If taking mucolytics, take after bronchodilators, but before aztreonam

Overdose

Aztreonam overdose is likely to intensify the drug’s side effects. There have been no reports of overdose with aztreonam injection or inhalation formulations. In case of systemic aztreonam overdose, aztreonam may be cleared from the blood by hemodialysis or peritoneal dialysis, if required.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Aztreonam has no known severe interactions with other drugs.
• Serious interactions of aztreonam include:
  • BCG vaccine live
  • cholera vaccine
  • microbiota oral
  • typhoid vaccine live
• Moderate interactions of aztreonam include:
  • bazedoxifene/conjugated estrogens
  • cefoxitin
  • conjugated estrogens
  • dienogest/estradiol valerate
  • digoxin
  • estradiol
  • estrogens conjugated synthetic
  • estropipate
  • mestranol
  • sodium picosulfate/magnesium oxide/anhydrous citric acid
• Mild interactions of aztreonam include:
  • amikacin
  • amoxicillin
  • balsalazide
  • biotin
  • cefadroxil
  • cefamandole
  • cefpirome
  • chloramphenicol
  • dicloxacillin
  • gentamicin
  • neomycin PO
  • pantothenic acid
  • paromomycin
  • pivmecillinam
  • probenecid
  • pyridoxine
  • pyridoxine (Antidote)
  • streptomycin
  • temocillin
  • thiamine
  • ticarcillin
  • tobramycin

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Animal reproductive studies have not revealed any evidence of drug-related fetal harm with the use of aztreonam during pregnancy, however, there are no adequate and well-controlled studies in pregnant women. Aztreonam must be used during pregnancy only if clearly needed, because animal studies are not always predictive of human response.
• Aztreonam is present in breastmilk in concentrations of less than 1% of that in the mother’s blood, and hence is unlikely to pose a risk to the breastfed infant. To eliminate the possibility of any risk, the nursing mother may consider temporary discontinuation of breastfeeding during treatment with aztreonam.

• Complete the course of aztreonam injections or inhalation therapy. Do not miss your appointment for injections or discontinue therapy if you feel better, it can decrease effectiveness of treatment and can also lead to development of drug-resistant bacteria.
• Inform your physician immediately if you develop hypersensitivity reactions to aztreonam.
• In case of overdose or suspected overdose, contact your physician or Poison Control.

Aztreonam injection

• Diarrhea is a common problem with antibiotic treatments, which should resolve with the completion of the therapy. Seek medical help if you have watery or bloody stools, with or without stomach cramps and fever. Symptoms can develop even up to two months after the last dose of antibiotic.

Inhaled aztreonam

• Follow instructions exactly if using inhalation formulation of aztreonam. Inhaled aztreonam should only be administered with the Altera Nebulizer System. Reconstitute aztreonam with the provided diluent only and do not mix other drugs with it.
• Complete the full 28-day course even if you feel better. If you miss a dose, take the prescribed 3 daily doses as long as the doses are at least 4 hours apart.
• If you use other inhaled medications, take a bronchodilator first, then mucolytic agent, and finally aztreonam.
• Report to your doctor if you experience new or worsening symptoms.
• Store aztreonam inhalation solution and the nebulizer safely out of reach of children.