Azactam

Monobactam Antibiotics
Respiratory Monobactam Antibiotics

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
Reconstitute with at least 3 mL of Sterile Water for Injection per g of aztreonam.
FURTHER DILUTION IS NECESSARY FOR IV INFUSION.
Shake immediately and vigorously.
Storage: Use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F).[44907]
 
Dilution
Further dilute the appropriate dose in a compatible IV solution.
Compatible IV solutions include 0.9% Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection, 5% Dextrose Injection, 10% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.2% Sodium Chloride Injection, Sodium Lactate (M/6) Injection, Inosol B and 5% Dextrose Injection, Isolyte E Injection, Isolyte E with 5% Dextrose Injection, Isolyte M with 5% Dextrose Injection, Normosol-R Injection, Normosol-R and 5% Dextrose Injection, Normosol-M and 5% Dextrose Injection, 5% Mannitol Injection, 10% Mannitol Injection, Lactated Ringers and 5% Dextrose Injection, and Plasma-Lyte M and 5% Dextrose Injection.
If using a volume control administration set, the final dilution of aztreonam should not exceed a concentration of 20 mg/mL.
Shake immediately and vigorously.
Storage: For solutions at concentrations not exceeding 20 mg/mL (2% w/v) and for solutions at concentrations exceeding 20 mg/mL (2% w/v) using Sterile Water for Injection or 0.9% Sodium Chloride Injection, use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F). For other solutions at concentrations exceeding 20 mg/mL (2% w/v), use promptly after preparation.[44907]
 
Frozen Pre-mixed Bags
Thaw frozen Galaxy containers at room temperature (25 degrees C or 77 degrees F) or under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Do not force thaw by immersion in water baths or by microwave irradiation. Check for leaks by squeezing bag firmly. Do not add supplementary medication.
Contents of the solution may precipitate in the frozen state and should dissolve with little or no agitation once the solution has reached room temperature.
Storage: The thawed solution is stable for 48 hours at room temperature or 14 days under refrigeration.[31042]
 
Intermittent IV Infusion:
Infuse appropriate dose IV over 20 to 60 minutes.[31042] [44907]
For neonates, an infusion time of 15 minutes has been recommended.[53249]
For premixed-bags, do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.[31042]
 
Intermittent Extended IV Infusion†:
NOTE: Administration by extended infusion is not FDA-approved.[31042] [44907]
Administering as an extended infusion (3-hour infusion) may increase the likelihood of pharmacodynamic target achievement in difficult to treat infections.
 
Intravenous (IV) Push
Powder Vials for Injection
Reconstitution
Reconstitute each vial with 6 to 10 mL of Sterile Water for Injection.
Shake immediately and vigorously.
Storage: Use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F).[44907]
 
Intermittent IV Push
Slowly inject directly into a vein or the tubing of a suitable administration set over 3 to 5 minutes.[44907]

Powder Vials for Injection
Reconstitution
Reconstitute vials with at least 3 mL of an appropriate diluent per g of aztreonam.
Appropriate diluents include Sterile Water for Injection, Sterile Bacteriostatic Water for Injection (with benzyl alcohol or with methyl- and polyparabens), 0.9% Sodium Chloride Injection, and Bacteriostatic Sodium Chloride (with benzyl alcohol) Injection.
Shake immediately and vigorously.
Storage: For solutions at concentrations not exceeding 20 mg/mL (2% w/v) and for solutions at concentrations exceeding 20 mg/mL (2% w/v) using Sterile Water for Injection or 0.9% Sodium Chloride Injection, use within 48 hours if kept at room temperature (15 to 30 degrees C or 59 to 98 degrees F) or within 7 days if kept under refrigeration (2 to 8 degrees C or 38 to 48 degrees F). For other solutions at concentrations exceeding 20 mg/mL (2% w/v), use promptly after preparation.[44907]
 
Intramuscular Injection
In adults, inject doses of 1 g or less deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).[44907]
According to the FDA-approved product labeling, there are insufficient data regarding intramuscular administration of aztreonam in pediatric patients; however, aztreonam has been administered IM to pediatric patients in clinical practice when acceptable IV access was not available. Inject deeply into a large muscle mass (e.g., anterolateral thigh). When multiple IM injections are necessary, rotate administration sites.[44907]
In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.[53249]
Aztreonam is well tolerated; do not admix with any local anesthetic agent.[44907]

Nebulized Solution
Reconstitution
Do not reconstitute aztreonam for inhalation until ready to administer a dose.
Gently tap the aztreonam vial so that the powder settles to the bottom of the vial.
Using the blue cap tab, slowly flip up the blue cap. Pull the blue cap down to a horizontal position, where the bottom of the blue cap faces up.
Slowly pull the blue cap in a counterclockwise direction until the metal seal opens and is completely removed. Do not twist the blue cap.
Carefully remove the rubber stopper.
Twist the tip off of the provided 1 mL sterile diluent (0.17% Sodium Chloride) ampule and squeeze contents into the aztreonam vial.
Gently swirl the vial until the contents have completely dissolved.[43523]
 
Administration
Have patient use a bronchodilator before administration of the aztreonam nebulized solution. A short-acting bronchodilator can be administered 15 minutes to 4 hours before aztreonam. Alternatively, a long-acting bronchodilator can be administered 30 minutes to 12 hours before aztreonam. For patients taking multiple inhaled therapies, the recommended order of administration is bronchodilator, mucolytic, and then aztreonam.
Administer aztreonam immediately after reconstitution using an Altera Nebulizer System only. Do not administer via any other nebulizer.
Do not mix any with any other drugs.
Administration typically takes 2 to 3 minutes via the nebulizer mouthpiece.[43523]

bronchospasm / Rapid / 0-3.0
GI bleeding / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
erythema multiforme / Delayed / 0-1.0
pancytopenia / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
seizures / Delayed / 0-1.0
C. difficile-associated diarrhea / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 0-20.0
wheezing / Rapid / 0-16.0
neutropenia / Delayed / 0-11.3
eosinophilia / Delayed / 0-6.3
thrombocytosis / Delayed / 0-3.6
erythema / Early / 0.5-2.9
phlebitis / Rapid / 0.5-2.1
hepatitis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
oral ulceration / Delayed / 0-1.0
candidiasis / Delayed / 0-1.0
pseudomembranous colitis / Delayed / 0-1.0
chest pain (unspecified) / Early / 0-1.0
dyspnea / Early / 0-1.0
anemia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
hypotension / Rapid / 0-1.0
premature ventricular contractions (PVCs) / Early / 0-1.0
confusion / Early / 0-1.0
encephalopathy / Delayed / 0-1.0
vaginitis / Delayed / 0-1.0
superinfection / Delayed / Incidence not known

cough / Delayed / 54.0-54.0
nasal congestion / Early / 0-16.0
fever / Early / 0-13.0
injection site reaction / Rapid / 0.5-12.0
abdominal pain / Early / 7.0-7.0
vomiting / Early / 1.0-6.0
rash / Early / 1.0-4.3
diarrhea / Early / 1.0-1.4
nausea / Early / 1.0-1.3
dysgeusia / Early / 0-1.0
halitosis / Early / 0-1.0
sneezing / Early / 0-1.0
diaphoresis / Early / 0-1.0
petechiae / Delayed / 0-1.0
purpura / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
headache / Early / 0-1.0
weakness / Early / 0-1.0
malaise / Early / 0-1.0
leukocytosis / Delayed / 0-1.0
flushing / Rapid / 0-1.0
vertigo / Early / 0-1.0
paresthesias / Delayed / 0-1.0
insomnia / Early / 0-1.0
dizziness / Early / 0-1.0
diplopia / Early / 0-1.0
tinnitus / Delayed / 0-1.0
arthralgia / Delayed / Incidence not known

Azactam, Cayston

Rx

Synthetic beta-lactam antibiotic; spectrum limited to aerobic gram-negative bacteria; no gram-positive or anaerobic activity; less nephrotoxic than aminoglycosides; not indicated for meningitis. Aztreonam for inhalation indicated for CF patients >= 7 years.

NOTE: The FDA has designated aztreonam solution for inhalation as an orphan drug for control of gram-negative bacteria in the respiratory tract of patients with cystic fibrosis and for the improvement of respiratory symptoms in patients with bronchiectasis and gram-negative bacteria in the airways.

75 mg inhaled by nebulizer 3 times daily (at least 4 hours apart) for 28 days in alternating 28-day periods. Aztreonam inhalation solution is FDA-approved for persons with an FEV1 of 25% to 75% predicted.

75 mg inhaled by nebulizer 3 times daily (at least 4 hours apart) for 28 days in alternating 28-day periods. Aztreonam inhalation solution is FDA-approved for persons with an FEV1 of 25% to 75% predicted.

2 g IV every 6 to 8 hours; doses of 2 to 3 g IV every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.

150 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 to 8 hours; doses of 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.  

90 to 150 mg/kg/day IV divided every 6 to 8 hours; doses of 200 to 300 mg/kg/day IV divided every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.

90 to 150 mg/kg/day IV divided every 6 to 8 hours; doses of 200 to 300 mg/kg/day IV divided every 6 hours may be necessary to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.

2 g IV every 6 to 8 hours.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.

30 mg/kg/dose IV every 6 to 8 hours.

30 mg/kg/dose IV every 6 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 12 hours.

2 g IV every 8 hours administered over 3 hours plus ceftazidime; avibactam.

500 mg to 1 g IV or IM every 8 to 12 hours. Treat for at least 48 hours after patient becomes asymptomatic or evidence of bacterial eradication.

30 mg/kg/dose (Max: 1 g/dose) IV every 8 hours.

30 mg/kg/dose IV every 6 to 8 hours.

1 g IV or IM every 8 to 12 hours or 2 g IV every 6 to 12 hours for 7 to 14 days with or without an aminoglycoside.

30 mg/kg/dose (Max: 1 g/dose) IV every 6 to 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

30 mg/kg/dose IV every 6 to 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

30 mg/kg/dose IV every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

30 mg/kg/dose IV every 6 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

30 mg/kg/dose IV every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

30 mg/kg/dose IV every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

2 g IV every 8 hours for at least 7 days.[34362] [64669]

30 mg/kg/dose IV (Max: 2 g/dose) every 6 to 8 hours for 5 to 7 days.

2 g IV every 8 hours for 7 days.[61215]

1 to 2 g IV or IM every 8 to 12 hours for moderately severe systemic infections. For severe, life-threatening infections, 2 g IV every 6 to 8 hours (Max: 8 g/day).

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.

30 mg/kg/dose IV every 6 to 8 hours.

30 mg/kg/dose IV every 6 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 12 hours.

1 to 2 g IV or IM every 8 to 12 hours for 5 to 7 days.

2 g administered over 3 hours IV every 8 hours for at least 7 days plus ceftazidime; avibactam.

1 or 2 g IV every 8 to 12 hours.

30 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 6 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 12 hours.

1 g IM every 8 to 12 hours.

2 g IV every 6 to 8 hours for 7 to 14 days for severe infections as empiric therapy. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

2 g administered over 3 hours IV every 8 hours plus ceftazidime; avibactam.

2 g IV every 6 to 8 hours.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.

30 mg/kg/dose IV every 6 to 8 hours.

30 mg/kg/dose IV every 6 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 8 hours.

30 mg/kg/dose IV every 12 hours.

1 or 2 g IV every 8 to 12 hours.

30 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.

1 g IM every 8 to 12 hours.

2 g IV every 6 to 8 hours.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours.

2 g IV as a single dose within 60 minutes prior to the surgical incision; or alternately, 1 g IV as a single dose for gynecologic procedures. Intraoperative redosing 4 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend aztreonam in combination with cefazolin, or for beta-lactam allergic patients, clindamycin or vancomycin, for urologic procedures involving implanted prosthesis. Aztreonam in combination with an appropriate antimicrobial with gram-positive activity (i.e., clindamycin or vancomycin) is also recommended as an alternate therapy for patients with a beta-lactam allergy undergoing gastrointestinal, biliary tract, uncomplicated appendectomy, colorectal, hysterectomy, or abdominal transplantion procedures.

30 mg/kg/dose IV as a single dose (Max: 2 g/dose) within 60 minutes prior to the surgical incision. Intraoperative redosing 4 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend aztreonam in combination with cefazolin, or for beta-lactam allergic patients, clindamycin or vancomycin, for urologic procedures involving implanted prosthesis. Aztreonam in combination with an appropriate antimicrobial with gram-positive activity (i.e., clindamycin or vancomycin) is also recommended as an alternate therapy for patients with a beta-lactam allergy undergoing gastrointestinal, biliary tract, uncomplicated appendectomy, colorectal, or abdominal transplantion procedures.

2 g IV every 6 to 8 hours or 1.5 g IV every 4 hours has been studied in combination with vancomycin or clindamycin. Aztreonam in combination with vancomycin is recommended in guidelines as an alternative in patients that have significant beta-lactam allergy.

50 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours in combination with other antimicrobials. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent, such as aztreonam, is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

2 g IV every 8 hours for 7 to 14 days as an alternative in cephalosporin-allergic patients; treat for at least 7 days after defervescence.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 to 14 days as an alternative in cephalosporin-allergic patients; treat for at least 7 days after defervescence.

1 to 2 g IV every 6 to 8 hours for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

30 mg/kg/dose IV every 6 to 8 hours for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

30 mg/kg/dose IV every 6 hours for 7 to 10 days.

30 mg/kg/dose IV every 8 hours for 7 to 10 days.

30 mg/kg/dose IV every 8 hours for 7 to 10 days.

30 mg/kg/dose IV every 12 hours for 7 to 10 days.

2 g intraperitoneally every 24 hours for 21 to 28 days.

1 g/L intraperitoneal loading dose, followed by 250 mg/L in each dialysate exchange. Treat for 21 to 28 days.

1 g/L intraperitoneal loading dose, followed by 250 mg/L in each dialysate exchange. Treat for 14 to 21 days.

1 to 2 g IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

30 mg/kg/dose IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

2 g administered over 3 hours IV every 8 hours for 3 to 7 days with ceftazidime; avibactam as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

2 g IV every 8 hours for 14 days with or without an aminoglycoside.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours for 14 days with or without an aminoglycoside.

2 g IV every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.

30 mg/kg/dose (Max: 2 g/dose) IV every 6 to 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.

†Indicates off-label use

No dosage adjustment is needed. The half-life of systemically administered aztreonam is only slightly prolonged in patients with hepatic impairment. The low systemic exposure of aztreonam for inhalation would not warrant dosage adjustments.

Dosage adjustment due to renal impairment is necessary for systemic dosage only. Nebulized aztreonam does not require dosage adjustment due to low systemic exposure.[31042] [44907] [43523]
 
The FDA-labeled dosage adjustment in adults with renal impairment reduces the dose and maintains the fixed dosing intervals.[31042] [44907]
CrCl more than 30 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 10 to 30 mL/minute/1.73 m2: After a normal loading dose, administer 50% of the standard dose and give at standard dosing intervals.
CrCl less than 10 mL/minute/1.73 m2: After a normal loading dose, administer 25% of the standard dose and give at standard dosing intervals.
 
Dosage adjustments in pediatric patients:
According to the FDA-approved product labeling, there are insufficient data in pediatric patients with renal failure to determine appropriate dosage adjustments.[44907] However, other experts recommend the following dosage adjustments [32569]:
GFR 30 to 50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 29 mL/minute/1.73 m2: 15 to 20 mg/kg/dose IV every 8 hours.
GFR less than 10 mL/minute/1.73 m2: 7.5 to 10 mg/kg/dose IV every 12 hours.
 
Intermittent hemodialysis
Aztreonam is cleared by hemodialysis with 27% to 58% of the dose removed.[32569] The FDA-approved dosage adjustment for adult hemodialysis patients is to give the normal loading dose followed by 25% of the usual dose given at the standard dosing interval. For serious or life-threatening infections, one-eighth of the initial dose should be given after each hemodialysis session in addition to maintenance dosing.[44907] For pediatric patients, 7.5 to 10 mg/kg/dose IV every 12 hours is recommended.[32569]
 
Peritoneal dialysis
For adults, administer 25% of the standard dose.[32569] For pediatric patients, 7.5 to 10 mg/kg/dose IV every 12 hours is recommended.[32569]
 
Continuous renal replacement therapy (CRRT)
For adults, a loading dose of 2 g IV is suggested for CRRT. Recommended doses for various types of CRRT include 1 to 2 g IV/IM every 12 hours for continuous venovenous hemofiltration (CVVH) and 1 g IV/IM every 8 hours or 2 g IV/IM every 12 hours for continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF).[32569] [42303] For pediatric patients, 100% of the dose is recommended.[32569]

Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aztreonam, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

Azactam/Aztreonam Intramuscular Inj Pwd F/Sol: 1g, 2g
Azactam/Aztreonam Intravenous Inj Pwd F/Sol: 1g, 2g
Cayston Respiratory (Inhalation) Pwd F/Recon: 75mg

225 mg/day nebulized; 8 g/day IV/IM is FDA-approved; however, 12 g/day IV has been used.

225 mg/day nebulized; 8 g/day IV/IM is FDA-approved; however, 12 g/day IV has been used.

225 mg/day nebulized; 120 mg/kg/day (Max: 8 g/day) IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day (Max: 12 g/day) IV has been used in patients with cystic fibrosis.

7 to 12 years: 120 mg/kg/day (Max: 8 g/day) IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day (Max: 12 g/day) IV has been used in patients with cystic fibrosis. The maximum nebulized dosage is 225 mg/day.
1 to 6 years: 120 mg/kg/day IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day IV has been used in patients with cystic fibrosis. Safety and efficacy of nebulization have not been established.

9 to 12 months: 120 mg/kg/day IV is the FDA-approved maximum dosage; however, up to 300 mg/kg/day IV has been used in patients with cystic fibrosis. Safety and efficacy of nebulization have not been established.
1 to 8 months: Safety and efficacy have not been established. Doses up to 120 mg/kg/day IV have been used off-label for most infections; up to 300 mg/kg/day IV has been used in patients with cystic fibrosis.

34 weeks gestation and older and 8 days and older: Safety and efficacy have not been established; however, doses up to 120 mg/kg/day IV have been used off-label.
34 weeks gestation and older and 0 to 7 days: Safety and efficacy have not been established; however, doses up to 90 mg/kg/day IV have been used off-label.
Younger than 34 weeks gestation and 8 days and older: Safety and efficacy have not been established; however, doses up to 90 mg/kg/day IV have been used off-label.
Younger than 34 weeks gestation and 0 to 7 days: Safety and efficacy have not been established; however, doses up to 60 mg/kg/day IV have been used off-label.

Unlike the penicillins and cephalosporins, aztreonam is a monobactam. It contains a sulfonic acid group that gives the beta-lactam of aztreonam its activity. Like the penicillins and cephalosporins, aztreonam is mainly bactericidal and inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. In particular, aztreonam preferentially binds to PBP-3 of the gram-negative rods, and the sulfonic acid group assists in the acetylation of PBP-3. Since PBP-3 is responsible for formation of the septum during cell division, aztreonam's inhibition of these proteins causes elongation of the bacteria, inhibition of bacterial cell division, and breakage of the cell wall, which results in cell lysis and death. Aztreonam has no affinity for the PBPs of gram-positive organisms and poor affinity for anaerobic PBPs. In vitro, aztreonam has little ability to induce chromosomally mediated beta-lactamase production, although the selection of preexisting resistant organisms is still possible during clinical use.[23602] [31042] [50323]
 
The susceptibility interpretive criteria for aztreonam are delineated by pathogen. The MICs are defined for Enterobacterales as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more (based on a dosage of 1 g IV every 8 hours). The MICs are defined for P. aeurginosa and non-Enterobacterales as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more (based on a dosage of 1 g IV every 6 hours or 2 g IV every 8 hours for P. aeurginosa). The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 2 mcg/mL or less.[63320] [63321]
 
Bacterial resistance to aztreonam occurs via hydrolysis by beta-lactamase, alteration of the PBP, and decreased intracellular permeability.[31042]

Aztreonam is administered via nebulization, intravenously, and intramuscularly. Approximately 56—65% of aztreonam is protein-bound. Systemic aztreonam is distributed into most body tissues and fluids including lungs, liver, kidneys, bone, uterus, ovary, intestine, saliva, sputum, bile, as well as peritoneal, pleural, pericardial, and synovial fluids. It reaches high enough concentrations within CSF to inhibit most Enterobacteriaceae when administered systemically, although it is not indicated for the treatment of meningitis. It also crosses the placenta.
 
Hepatic metabolism is a minor pathway of excretion. Aztreonam and the inactive metabolites are excreted primarily into the urine via tubular secretion and glomerular filtration. A small percentage is excreted in feces. The drug is also excreted in breast milk. The elimination half-life of aztreonam is 1.7 hours after systemic administration and 2.1 hours after nebulization in patients with normal renal function. Concomitant administration of probenecid or furosemide and aztreonam does not result in clinically significant increases in aztreonam serum concentrations.

Aztreonam is poorly absorbed from the GI tract.

After single aztreonam 500—1000 mg IV doses, the serum levels exceeded the MIC90 for Neisseria sp, H. influenzae, most genera of Enterobacteriaceae and 80% of Enterobacter sp. for 8 hours. For P. aeruginosa, a single 2 g IV dose of aztreonam will maintain levels exceeding the MIC90 for 4—6 hours. The same doses of aztreonam result in urine concentrations of aztreonam that exceed the MIC90 for these organisms for up to 12 hours. Approximately 60—70% of an IV or IM dose of aztreonam is recovered in the urine in 8 hours. Urinary excretion of a single dose is essentially complete 12 hours after the injection.

Peak plasma levels of aztreonam occur within 60 minutes after an IM dose. Serum concentrations are comparable between IM and IV dosing at 1 hour (1.5 hours from the start of the IV infusion) after the dose. Following single aztreonam 500—1000 mg IM doses, the serum levels exceeded the MIC90 for Neisseria sp, H. influenzae, most genera of Enterobacteriaceae, and 80% of Enterobacter sp. for 8 hours. The same doses of aztreonam result in urine concentrations of aztreonam that exceed the MIC90 for these organisms for up to 12 hours. Approximately 60—70% of an IV or IM dose of aztreonam is recovered in the urine in 8 hours. Urinary excretion of a single dose is essentially complete 12 hours after the injection.

Sputum and plasma concentrations exhibited considerable variability between patients receiving nebulized aztreonam in clinical trials. The mean sputum concentration 10 minutes after the first dose of nebulized aztreonam (75 mg) was 726 mcg/g. In patients receiving nebulized aztreonam 3 times daily, mean sputum concentrations 10 minutes after dose administration on days 0, 14, and 28 were 984 mcg/g, 793 mcg/g, and 715 mcg/g, respectively, indicating no drug accumulation. The mean peak plasma concentration one hour after the first dose of nebulized aztreonam was 0.59 mcg/mL. Mean peak plasma concentrations in patients receiving nebulized aztreonam 3 times daily were 0.55 mcg/mL, 0.67 mcg/mL, and 0.65 mcg/mL on days 0, 14, and 28, respectively. These are low systemic concentrations compared to peak serum concentrations after an IV dose (approximately 54 mcg/mL after a 500 mg dose). Evaluation of plasma and urine concentrations indicates a low systemic absorption of nebulized aztreonam. Approximately 10% of the total nebulized dose is excreted in the urine as unchanged drug compared to 60—65% after IV administration. The elimination half-life of nebulized aztreonam is 2.1 hours.

Use aztreonam during pregnancy only if clearly needed. Data on aztreonam use during pregnancy are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There have been no adequate, well-controlled studies of aztreonam in pregnant women. Aztreonam crosses the placenta and enters fetal circulation. In animal studies with aztreonam for injection, there was no evidence of developmental toxicity or drug-induced changes in maternal, fetal, or neonatal parameters. Systemic absorption of aztreonam after inhaled administration is expected to be minimal. There are risks to the mother associated with cystic fibrosis in pregnancy; cystic fibrosis may increase the risk for preterm delivery.

Previous American Academy of Pediatrics (AAP) recommendations considered aztreonam as usually compatible with breast-feeding. Aztreonam is excreted in breast milk at very low concentrations after systemic administration. After a single 1 g IM dose in 6 women, average peak milk concentration, occurring 6 hours after the dose, was 0.3 mg/L. After a single 1 g IV dose in 6 other women, average peak milk concentration, occurring 2.4 hours after the dose was 0.2 mg/L. Aztreonam was detectable in milk between 2 and 8 hours after an IM dose and 1.5 and 8 hours after an IV dose. In another report, a single 1 g IV dose produced milk concentrations ranging from 0.4 to 1 mg/L at 1 to 5 hours after the dose with little variation in milk concentrations during this time in each woman. On average, concentrations were slightly higher 2 hours after the dose, but the peak concentrations occurred at various times between 1 and 4 hours. Peak plasma concentrations of aztreonam after nebulization are approximately 1% of peak concentrations observed after aztreonam 500 mg IV administration. There are no data on the effects of aztreonam on the breast-fed infant or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for aztreonam and any potential adverse effects on the breast-fed child from aztreonam or the underlying maternal condition.