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Aztreonam

Class: Monobactams
Chemical Name: [2S-[2α,3β(Z)]]-2-[[[1-(2-Amino-4-thiazolyl)-2-[2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid
CAS Number: 78110-38-0
Brands: Azactam, Cayston

Medically reviewed by Drugs.com on Sep 27, 2021. Written by ASHP.

Introduction

Antibacterial; monocyclic β-lactam antibiotic; monobactam.

Uses for Aztreonam

Bone and Joint Infections

Treatment of bone and joint infections (including osteomyelitis or septic arthritis) caused by susceptible gram-negative bacteria, including Enterobacter, Escherichia coli, Haemophilus influenzae, Klebsiella, Proteus mirabilis, Pseudomonas aeruginosa, or Serratia marcescens.

If gram-positive bacteria known or suspected to also be involved, regimen should also include an antistaphylococcal anti-infective (e.g., penicillinase-resistant penicillin, vancomycin).

IDSA states aztreonam is an alternative for treatment of native vertebral osteomyelitis caused by Ps. aeruginosa if a drug of first choice (i.e., cefepime, meropenem, doripenem) cannot be used because of severe penicillin allergy and ciprofloxacin cannot be used because of quinolone-resistant strains.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of osteomyelitis.

Gynecologic Infections

Treatment of gynecologic infections (including endometritis and pelvic cellulitis) caused by susceptible gram-negative bacteria, including Enterobacter (including E. cloacae), E. coli, K. pneumoniae, or P. mirabilis.

Do not use alone for empiric treatment of gynecologic infections since these usually are polymicrobial and frequently are mixed aerobic-anaerobic bacterial infections. Clindamycin or metronidazole generally used concomitantly if aztreonam used for initial treatment of gynecologic infections.

Intra-abdominal Infections

Treatment of intra-abdominal infections (including peritonitis) caused by susceptible gram-negative bacteria, including Citrobacter (including C. freundii), Enterobacter (including E. cloacae), E. coli, Klebsiella (including K. pneumoniae), Ps. aeruginosa, or Serratia (including S. marcescens).

Do not use alone for empiric treatment of intra-abdominal infections since these usually are polymicrobial and frequently are mixed aerobic-anaerobic bacterial infections. Clindamycin or metronidazole generally used concomitantly if aztreonam used for initial treatment of intra-abdominal infections.

For initial empiric treatment of high-risk or severe community-acquired, extrabiliary, complicated intra-abdominal infections in adults, IDSA states that aztreonam in conjunction with metronidazole is an alternative regimen, but an additional anti-infective active against gram-positive bacteria is recommended pending results of in vitro culture and susceptibility tests.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of intra-abdominal infections.

Intraperitoneal: Has been used for treatment of peritonitis in patients undergoing CAPD. Some clinicians suggest that intraperitoneal anti-infectives are preferred over IV anti-infectives for empiric treatment of peritonitis in CAPD patients; regimen should provide coverage against both gram-positive and gram-negative bacteria pending results of in vitro culture and susceptibility testing. Intraperitoneal vancomycin in conjunction with intraperitoneal aztreonam has been used; aztreonam recommended as an alternative for gram-negative coverage in CAPD patients allergic to cephalosporins.

Respiratory Tract Infections

Treatment of lower respiratory tract infections (including pneumonia and bronchitis) caused by susceptible gram-negative bacteria, including Enterobacter, E. coli, H. influenzae, K. pneumoniae, Ps. aeruginosa, P. mirabilis, or S. marcescens.

Also has been used for treatment of lower respiratory tract infections caused by susceptible Citrobacter, Hafnia, K. oxytoca, Morganella, P. vulgaris, Providencia stuartii, or Moraxella catarrhalis.

Do not use alone for empiric treatment of lower respiratory tract infections since these infections frequently are caused by gram-positive and/or anaerobic bacteria.

Clindamycin in conjunction with aztreonam has been used for initial empiric treatment of lower respiratory tract infections (especially nosocomial infections).

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of respiratory tract infections, including community-acquired pneumonia (CAP).

Oral inhalation via nebulization: Used to improve respiratory symptoms in cystic fibrosis patients ≥7 years of age with Ps. aeruginosa in the lungs. Safety and efficacy not established in pediatric patients <7 years of age, in patients with FEV1 <25% or >75% of predicted, or in patients colonized with Burkholderia cepacia.

Septicemia

Treatment of septicemia caused by susceptible gram-negative bacteria, including Enterobacter, E. coli, K. pneumoniae, Ps. aeruginosa, P. mirabilis, or S. marcescens.

Also has been used for treatment of septicemia caused by susceptible Citrobacter or H. influenzae.

Skin and Skin Structure Infections

Treatment of skin and skin structure infections (including those associated with postoperative wounds, ulcers, and burns) caused by susceptible gram-negative bacteria, including Citrobacter, Enterobacter, E. coli, K. pneumoniae, P. mirabilis, Ps. aeruginosa, or S. marcescens.

Adjunct to surgery in management of abscesses, cutaneous infections, infections complicating hollow viscus perforations, or infections of serous surfaces caused by susceptible gram-negative aerobic bacteria.

Consult current IDSA clinical practice guidelines available at [Web] for additional information on management of skin and skin structure infections.

Urinary Tract Infections (UTIs)

Treatment of uncomplicated or complicated UTIs (including pyelonephritis and initial or recurrent cystitis) caused by susceptible gram-negative bacteria, including Citrobacter, E. cloacae, E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, Ps. aeruginosa, or S. marcescens.

Also has been used for treatment of UTIs caused by susceptible E. aerogenes, Morganella morganii, P. vulgaris, or Providencia.

Has been effective for treatment of cystitis or pyelonephritis caused by gram-negative aerobic bacteria resistant to aminopenicillins, first or second generation cephalosporins, and/or aminoglycosides. Although aztreonam generally is associated with less toxicity than aminoglycosides, colonization or superinfection with gram-positive bacteria (especially Enterococcus faecalis) has been reported more frequently with aztreonam than with aminoglycosides.

Perioperative Prophylaxis

Perioperative prophylaxis in patients undergoing certain surgical procedures in which aerobic gram-negative bacteria are common pathogens; used in conjunction with other anti-infectives.

Regimen of vancomycin (or clindamycin) in conjunction with aztreonam recommended as an alternative for perioperative prophylaxis in patients undergoing gastroduodenal or biliary tract surgery, hysterectomy (vaginal or abdominal), or certain organ transplant procedures (liver, pancreas, pancreas-kidney). Regimen of clindamycin and aztreonam also considered an alternative in patients undergoing appendectomy, colorectal or small intestine surgery, or urologic surgery involving an implanted prosthesis.

Some clinicians recommend concomitant use of an anti-infective active against enteric gram-negative bacilli (e.g., aztreonam, aminoglycoside, fluoroquinolone) when vancomycin used for perioperative prophylaxis in patients undergoing neurosurgery or cardiac, orthopedic, or vascular surgery.

Empiric Therapy in Febrile Neutropenic Patients

Has been used in conjunction with vancomycin (with or without amikacin) for empiric anti-infective therapy in febrile granulocytopenic adults. Because gram-positive bacteria (especially Staphylococcus epidermidis) reported with increasing frequency in febrile granulocytopenic patients and because aztreonam is inactive against these organisms, an anti-infective active against staphylococci (e.g., vancomycin) also should be used if aztreonam is used for empiric therapy in these patients. A regimen of aztreonam and vancomycin is considered an alternative empiric regimen in patients with immediate-type penicillin hypersensitivity.

Consult published protocols for treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.

Aztreonam Dosage and Administration

Administration

Parenteral: Administer by IV injection or infusion or by deep IM injection.

Oral inhalation: Administer by oral inhalation via nebulization.

Has been administered intraperitoneally in dialysis fluid.

IV route preferred (instead of IM) in patients with septicemia, localized parenchymal abscess (such as intra-abdominal abscess), peritonitis, or other severe systemic or life-threatening infection and when individual doses >1 g are to be administered.

Administer commercially available frozen premixed aztreonam injection in dextrose only by IV infusion.

Administer commercially available powder for inhalation solution only by oral inhalation via nebulization.

IV Injection

Reconstitution

For direct intermittent IV injection, reconstitute single-dose vials containing 500 mg, 1 g, or 2 g by adding 6–10 mL of sterile water for injection. Shake immediately and vigorously after diluent is added.

Rate of Administration

Inject appropriate dose of reconstituted solution slowly over a period of 3–5 minutes either directly into a vein or into the tubing of a compatible IV solution.

IV Infusion

When given IV via a common administration tubing used to administer another drug, especially one incompatible with aztreonam, flush tubing before and after aztreonam administration with an IV infusion solution compatible with both drugs; do not give the drugs simultaneously. When a Y-type IV administration set used, give careful attention to the calculated volume of aztreonam solution to ensure that entire dose is infused.

Reconstitution and Dilution

For intermittent IV infusion, reconstitute single-dose vial containing 500 mg, 1 g, or 2 g of aztreonam by adding at least 1.5, 3, or 6 mL, respectively, of sterile water for injection. Shake immediately and vigorously after diluent is added. Then, dilute further by adding reconstituted solution to a compatible IV infusion solution to provide a solution with a final concentration ≤20 mg/mL. A volume control IV administration set may be used to add the appropriate dose of reconstituted aztreonam solution to the compatible IV infusion solution during administration; this final dilution should provide a solution with a concentration ≤20 mg/mL.

Alternatively, thaw the commercially available premixed injection (frozen) at room temperature (25° C) or in a refrigerator (2–8°C); do not thaw by immersion in a water bath or by exposure to microwave radiation. A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature. Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact or leaks are found. Do not use in series connections with other plastic containers; such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete. Manufacturer recommends that the IV administration set be replaced every 48 hours.

Rate of Administration

Give by IV infusion over 20–60 minutes.

IM Injection

Inject appropriate dose of reconstituted IM solution deeply into a large muscle (e.g., upper outer quadrant of gluteus maximus, lateral part of thigh) using usual techniques and precautions.

Generally well tolerated when given IM; do not admix with local anesthetic agents.

Reconstitution

For IM injection, reconstitute single-dose vial containing 500 mg, 1 g, or 2 g by adding at least 1.5, 3, or 6 mL, respectively, of sterile water for injection, 0.9% sodium chloride injection, bacteriostatic water for injection (with benzyl alcohol or parabens), or bacteriostatic sodium chloride injection (with benzyl alcohol). Shake immediately and vigorously after diluent is added.

Oral Inhalation via Nebulization

For administration by oral inhalation via nebulization, aztreonam is commercially available in a kit containing single-dose vials of aztreonam powder for inhalation solution and single-dose ampuls of 0.17% sodium chloride diluent.

Reconstitute aztreonam powder for inhalation solution using only the diluent provided by the manufacturer; do not reconstitute until it is time to administer a dose.

Following reconstitution, administer the inhalation solution via nebulization using only an Altera nebulizer system. Do not administer using any other type of nebulizer and do not administer IV or IM.

Patients receiving aztreonam oral inhalation therapy should use a bronchodilator before aztreonam is administered. Short-acting bronchodilators can be taken between 15 minutes and 4 hours prior to each aztreonam dose. Alternatively, long-acting bronchodilators can be taken 0.5–12 hours prior to administration of aztreonam.

For patients taking multiple inhaled therapies, recommended order of administration is a bronchodilator, mucolytics, and, lastly, aztreonam.

Reconstitution

To prepare a dose, add the contents of a single-dose ampul of diluent provided by the manufacturer to a single-dose vial of aztreonam lyophilized powder for inhalation solution. Gently swirl vial until powder dissolves completely.

Administer the inhalation solution via nebulization immediately after reconstitution.

Nebulization

Pour reconstituted aztreonam inhalation solution into handset of Altera nebulizer system and turn unit on. Do not mix reconstituted inhalation solution with any other drug in the Altera nebulizer handset.

Patient should be seated in a relaxed, upright position. Place mouthpiece of nebulizer handset into the mouth; with lips closed around mouthpiece, patient should breathe normally through the mouthpiece.

About 2–3 minutes are required to administer the complete dose of reconstituted inhalation solution using the nebulizer system.

Consult manufacturer's information for additional information on administration via the nebulizer. Consult information included with the nebulizer system for instructions on testing nebulizer functionality and cleaning the handset.

Dosage

Dosage and route of administration should be determined by type and severity of infection, susceptibility of causative organism, and condition of the patient. Do not use dosages lower than those usually recommended.

For most infections, continue parenteral therapy for at least 48 hours after patient becomes asymptomatic or evidence of eradication of infection obtained. Persistent infections may require several weeks of treatment.

Pediatric Patients

General Dosage for Neonates†
IV or IM

Neonates ≤7 days of age: AAP recommends 30 mg/kg every 12 hours in those weighing ≤2 kg or 30 mg/kg every 8 hours in those weighing >2 kg.

Neonates 8–28 days of age: AAP recommends 30 mg/kg every 8–12 hours in those weighing ≤2 kg or 30 mg/kg every 6 hours in those weighing >2 kg.

Pseudomonas infections in neonates ≤28 days of age: AAP states it may be necessary to use doses of 50 mg/kg.

General Pediatric Dosage
IV

Children ≥9 months of age: Manufacturer recommends 30 mg/kg every 8 hours for treatment of mild to moderate infections or 30 mg/kg every 6 or 8 hours for treatment of moderate to severe infections.

Children beyond the neonatal period: AAP recommends 90 mg/kg daily given in 3 divided doses for mild to moderate infections or 90–120 mg/kg daily given in 3 or 4 divided doses for severe infections.

Children with cystic fibrosis: Dosage of 50 mg/kg every 6 or 8 hours (i.e., 150–200 mg/kg daily) suggested by some clinicians.

IM

Children >1 month of age: AAP recommends 90 mg/kg daily given in 3 divided doses for mild to moderate infections or 90–120 mg/kg daily given in 3 or 4 divided doses for severe infections.

Intra-abdominal Infections
IV

90–120 mg/kg daily given in divided doses every 6–8 hours recommended by IDSA. Usual duration for complicated infections is 4–7 days, unless it is difficult to achieve adequate source control.

Cystic Fibrosis Patients with Ps. aeruginosa
Oral Inhalation via Nebulization

Children ≥7 years of age: 75 mg 3 times daily for 28 days. Take doses at least 4 hours apart (e.g., in the morning, after school, at bedtime). Follow 28-day treatment with 28-day period without the drug.

In clinical trials, up to 9 courses used; each course consisted of 28 days of aztreonam oral inhalation therapy (75 mg 3 times daily), followed by 28 days without such therapy.

Adults

General Adult Dosage
Moderately Severe Systemic Infections
IV or IM

1 or 2 g every 8 or 12 hours.

Severe Systemic or Life-threatening Infections
IV

2 g every 6 or 8 hours.

Bone and Joint Infections†
IV

Osteomyelitis caused by Ps. aeruginosa: 2 g every 8 hours for 6 weeks recommended by IDSA.

Intra-abdominal Infections
IV

1–2 g every 6–8 hours recommended by IDSA. Usual duration for complicated infections is 4–7 days, unless it is difficult to achieve adequate source control.

Urinary Tract Infections (UTIs)
IV or IM

500 mg or 1 g every 8 or 12 hours.

Uncomplicated UTIs usually treated for 5–10 days; complicated UTIs usually treated for ≥10–18 days.

Perioperative Prophylaxis†
IV or IM

2 g within 1 hour prior to initial incision. During prolonged procedures (>4 hours) or if major blood loss occurs, may give additional intraoperative doses every 4 hours.

Duration of prophylaxis should be <24 hours for most procedures; no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.

Cystic Fibrosis Patients with Ps. aeruginosa
Oral Inhalation via Nebulization

75 mg 3 times daily for 28 days. Take doses at least 4 hours apart (e.g., in the morning, after school, at bedtime). Follow 28-day treatment with 28-day period without the drug.

In clinical trials, up to 9 courses used; each course consisted of 28 days of aztreonam oral inhalation therapy (75 mg 3 times daily), followed by 28 days without such therapy.

Peritonitis in Patients Undergoing CAPD†
IV and/or Intraperitoneal†

1-g loading dose given IV followed by maintenance doses of 500 mg given intraperitoneally in 2 L of dialysate every 6 hours.

Alternatively, intraperitoneal loading dose of 1 g per L of dialysate followed by intraperitoneal maintenance doses of 250 mg per L of dialysate.

Prescribing Limits

Pediatric Patients

Treatment of Infections
IV

Maximum recommended in pediatric patients ≥9 months of age is 120 mg/kg daily, but higher dosage may be warranted in those with cystic fibrosis.

Adults

Treatment of Infections
IV or IM

Maximum 8 g daily.

Special Populations

Hepatic Impairment

Treatment of Infections
IV or IM

Dosage adjustments probably not needed in patients with stable primary biliary cirrhosis or other chronic hepatic disease, unless renal function also impaired. Serum half-life only slightly prolonged in patients with hepatic impairment.

Although some clinicians recommend dosage be decreased by 20–25% in patients with alcoholic cirrhosis, especially if long-term therapy required, others suggest this decrease not needed, unless renal function also impaired.

Renal Impairment

Treatment of Infections
IV or IM

Adults with Clcr ≤30 mL/minute: Modify doses and/or frequency of administration based on degree of renal impairment.

Pediatric patients with impaired renal function: Data insufficient to date to make dosage recommendations.

Scr alone may not be sufficiently accurate to assess degree of renal impairment, especially in geriatric adults; dosage preferably should be based on patient’s measured or estimated Clcr.

Adults with Clcr 10–30 mL/minute per 1.73 m2: 1- or 2-g loading dose followed by maintenance doses equal to one-half the usual dose (i.e., 250 mg, 500 mg, or 1 g) given at the usual dosage intervals.

Adults with Clcr <10 mL/minute per 1.73 m2: Loading dose equal to the usual dose (i.e., 500 mg, 1 g, or 2 g) followed by maintenance doses equal to one-fourth the usual dose (i.e., 125 mg, 250 mg, or 500 mg) given at the usual dosage intervals.

Adults undergoing hemodialysis: Loading dose equal to the usual dose (i.e., 500 mg, 1 g, or 2 g) followed by maintenance doses equal to one-fourth the usual dose (i.e., 125 mg, 250 mg, or 500 mg) given at the usual dosage intervals. In those with serious or life-threatening infections, also give a supplemental dose equal to one-eighth the initial dose (i.e., 62.5 mg, 125 mg, or 250 mg) immediately after each dialysis period.

Adults undergoing CAPD: Some clinicians suggest IV loading dose equal to the usual dose (i.e., 500 mg, 1 g, or 2 g) followed by maintenance doses equal to one-fourth the usual dose (i.e., 125 mg, 250 mg, or 500 mg) given at the usual dosage intervals.

Oral Inhalation via Nebulization

Mild, moderate, or severe renal impairment: Dosage adjustments not needed.

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Monitor renal function; make appropriate dosage adjustments if necessary. (See Renal Impairment under Dosage and Administration.)

Cautions for Aztreonam

Contraindications

  • Hypersensitivity to aztreonam or any component in the formulation.

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible bacteria (e.g., S. aureus, E. faecalis) or fungi. Institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all systemic anti-infectives, including aztreonam, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to the development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible. Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Sensitivity Reactions

Hypersensitivity Reactions

IV or IM: Immediate hypersensitivity reactions, including anaphylaxis, bronchospasm, generalized urticaria with or without palpebral and lingual edema and respiratory impairment, and a severe episode of shock, rash, and eosinophilia, reported. Toxic epidermal necrolysis reported rarely.

Oral inhalation via nebulization: Rash reported. Allergic reactions with facial rash, facial swelling, and throat tightness also reported.

Hypersensitivity reactions to aztreonam may occur in patients with or without prior exposure to the drug.

If hypersensitivity reaction occurs, discontinue aztreonam and initiate appropriate treatment (e.g., vasopressors, antihistamines, corticosteroids, maintenance of ventilation). Serious hypersensitivity reactions may require epinephrine and other emergency measures.

Cross-Hypersensitivity

Consider possibility that cross-sensitivity to aztreonam may occur in patients with history of hypersensitivity to other β-lactam antibiotics.

Partial cross-allergenicity occurs among bicyclic β-lactam antibiotics (e.g., penicillins, cephalosporins, cephamycins). Although there appears to be little cross-allergenicity between aztreonam and bicyclic β-lactam antibiotics, hypersensitivity reactions to aztreonam (e.g., localized or urticarial rash, pharyngeal edema) have occurred rarely when the drug was used in patients with a history of hypersensitivity to penicillins and/or cephalosporins. Cross-allergenicity between ceftazidime and aztreonam has been reported in some individuals. In studies that included individuals with documented immediate (IgE-mediated) or nonimmediate (T cell-mediated) hypersensitivity to penicillins who had positive skin test reactions to at least 1 penicillin reagent, all individuals had negative skin test reactions to aztreonam and there were no reactions to aztreonam in those individuals willing to receive an IM aztreonam challenge.

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to β-lactam antibiotics, other drugs, or allergens. Use with caution in patients hypersensitive to β-lactam antibiotics (e.g., penicillins, cephalosporins, cephamycins).

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of aztreonam and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Because aztreonam has little or no activity against gram-positive bacteria and anaerobes, another anti-infective active against such bacteria should be used concomitantly if IV or IM aztreonam used empirically in infections that may involve gram-positive bacteria or anaerobes (e.g., gynecologic, intra-abdominal, or respiratory tract infections).

Precautions Related to Oral Inhalation via Nebulization

Use only to treat patients with cystic fibrosis who are known to have Ps. aeruginosa in the lungs. Use in the absence of known Ps. aeruginosa infection unlikely to provide benefit and increases risk of development of drug-resistant bacteria.

Safety and efficacy not established in pediatric patients <7 years of age, in patients with FEV1 <25% or >75% of predicted, or in patients colonized with Burkholderia cepacia.

Consider that bronchospasm is a known complication associated with nebulized therapies, including aztreonam. In clinical trials in patients pretreated with a bronchodilator, a reduction of ≥15% in FEV1 reported in 3% of patients immediately following a dose of aztreonam given by oral inhalation via nebulization.

In clinical trials, some patients with increases in FEV1 during 28-day course of aztreonam oral inhalation therapy were sometimes treated for pulmonary exacerbations when FEV1 declined after the treatment period. When evaluating whether change in FEV1 after treatment is caused by a pulmonary exacerbation, consider patient's baseline FEV1 measured prior to initiation of aztreonam oral inhalation therapy and presence of other symptoms.

Instruct patients to use a bronchodilator prior to administration of aztreonam inhalation solution. In patients receiving several inhaled drugs, recommended order is bronchodilator, mucolytics, and, lastly, aztreonam. (See Oral Inhalation via Nebulization under Dosage and Administration.)

Specific Populations

Pregnancy

Category B.

IV, IM, or oral inhalation via nebulization: No adequate and controlled studies to date in pregnant women. Do not use during pregnancy unless clearly needed.

Crosses placenta in pregnant women and enters fetal circulation.

Lactation

IV or IM: Low concentrations distributed into milk. Consider temporarily discontinuing breast-feeding during aztreonam therapy.

Oral inhalation via nebulization: Manufacturer states unlikely to pose risk to breast-feeding infants since peak plasma concentrations following 75-mg dose by oral inhalation via nebulization are approximately 1% of peak plasma concentrations reported following 500-mg IV dose.

Pediatric Use

IV or IM: Use in children 9 months to 16 years of age supported by evidence from adequate and well-controlled studies in adults with additional efficacy, safety, and pharmacokinetic data from noncomparative clinical studies in pediatric patients. Adverse effects reported in pediatric patients similar to those reported in adults.

IV or IM: Data insufficient regarding treatment of septicemia or skin and skin structure infections (where skin infection known or suspected to be caused by H. influenzae type b) in pediatric patients <9 months of age. Data also insufficient regarding IM route in pediatric patients or use of the drug in pediatric patients with impaired renal function.

IV or IM: Higher dosage may be warranted in pediatric patients with cystic fibrosis.

Oral inhalation via nebulization: Safety and efficacy not established in pediatric patients <7 years of age; has been used for treatment of newly acquired Ps. aeruginosa respiratory tract infections in a limited number of cystic fibrosis patients 3 months through 6 years of age without unusual adverse effects. In clinical trials evaluating aztreonam inhalation therapy in cystic fibrosis patients ≥7 years of age, pyrexia reported more frequently in pediatric patients than in adults.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Select IV or IM dosage with caution because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients.

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function. Since geriatric patients are more likely to have renal impairment, monitor renal function and adjust IV or IM dosage if needed.

Hepatic Impairment

Monitor hepatic function; adjustment of IV or IM dosage probably not needed, unless renal function also impaired. (See Hepatic Impairment under Dosage.)

Renal Impairment

Monitor renal function. Adjust IV or IM dosage is adults based on degree of renal impairment. (See Renal Impairment under Dosage.)

Common Adverse Effects

IV or IM: Local reactions at injection site (e.g., phlebitis/thrombophlebitis following IV administration or discomfort/swelling following IM administration); GI effects (diarrhea, nausea, vomiting); hypersensitivity (rash).

Oral inhalation via nebulization: Cough, nasal congestion, wheezing, bronchospasm, pharyngolaryngeal pain, pyrexia, chest discomfort, rash, abdominal pain, vomiting.

Interactions for Aztreonam

Drug interactions based on parenteral aztreonam. Formal interaction studies not conducted to date using aztreonam by oral inhalation via nebulization.

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Aminoglycosides

No clinically important effects on aztreonam pharmacokinetics

In vitro evidence of additive or synergistic antibacterial effects against Ps. aeruginosa and some strains of Ps. cepacia Ps. fluorescens, or Ps. maltophilia

In vitro evidence of synergistic antibacterial effects against Enterobacteriaceae (e.g., Enterobacter, E. coli, Klebsiella, Serratia)

In vitro synergism reported occasionally against Acinetobacter, but usually only additive or indifferent

Indifference reported against gram-positive bacteria (e.g., S. aureus, S. epidermidis, E. faecalis)

Monitor renal function, especially if high aminoglycoside dosage used or if therapy is prolonged; risk of aminoglycoside-associated nephrotoxicity and ototoxicity

Chloramphenicol

In vitro studies using K. pneumoniae indicate chloramphenicol can antagonize bactericidal activity of aztreonam

If used concomitantly, some clinicians suggest administering chloramphenicol a few hours after aztreonam; necessity of this precaution not established

Clavulanic acid

In vitro evidence of synergistic effects against some β-lactamase-producing Enterobacter, Klebsiella, or B. fragilis; antagonism also may occur

Concomitant use does not alter in vitro susceptibility of S. aureus to aztreonam since resistance to the drug in these organisms is intrinsic

Clindamycin

Possible increased total urinary excretion of aztreonam, but other pharmacokinetic parameters not affected

In vitro evidence of synergistic effects against some strains of E. coli, Klebsiella, or Enterobacter, indifferent or additive effects reported more frequently

Indifferent or slightly additive effects reported against anaerobic bacteria

Not considered clinically important

Furosemide

Possible increased serum aztreonam concentrations

Not considered clinically important

β-lactam antibiotics

Nafcillin: No clinically important pharmacokinetic interactions

In vitro evidence of additive or synergistic antibacterial effects with some β-lactams (piperacillin, cefotaxime) against some strains of Ps. aeruginosa; antagonism with imipenem against Ps. aeruginosa

In vitro evidence of indifferent or only slightly additive effects with some β-lactams (ampicillin, piperacillin, cefotaxime) against Enterobacteriaceae, including Enterobacter, E. coli, S. marcescens, or Klebsiella

In vitro evidence of synergism with cefoxitin against some strains of Enterobacter, E. coli, Klebsiella, S. marcescens, Salmonella, or Shigella; antagonism also reported against some Enterobacter or S. marcescens

Because of potential for antagonism, do not use β-lactams that are potent inducers of β-lactamase production (e.g., cefoxitin, imipenem) concomitantly with aztreonam

Metronidazole

Possible decreased peak serum concentrations of aztreonam; other pharmacokinetic parameters not affected

In vitro evidence of indifferent or slightly additive effects against anaerobic bacteria

Not considered clinically important

Probenecid

Decreased rate of renal tubular secretion of aztreonam and increased aztreonam concentrations: decreased binding of aztreonam to plasma proteins

Not sufficient to be of therapeutic benefit

Tests for glucose

Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)

Aztreonam Pharmacokinetics

Absorption

Bioavailability

IM: Rapidly and completely absorbed following IM administration; peak serum concentrations generally attained within 1 hour after an IM dose. Peak serum concentrations attained with IM dose are slightly lower than those attained with equivalent IV dose, but serum aztreonam concentrations ≥1 hour after dosing are similar.

Oral inhalation via nebulization: Variable concentrations enter systemic circulation; accumulation does not occur following multiple doses.

Special Populations

IV: Pharmacokinetics in pediatric patients ≥9 months of age similar to those in adults.

Distribution

Extent

IV or IM: Widely distributed into body tissues and fluids. Distributed into skeletal muscle, adipose tissue, skin, bone, gallbladder, liver, lungs, kidneys, atrial appendage, intestines, prostatic tissue, myometrium, endometrium, fallopian tubes, ovaries, and cervical and vaginal tissue. Also distributed into saliva, sputum, bronchial secretions, aqueous humor, and bile, and into pericardial, pleural, peritoneal, synovial, and blister fluids.

IV: Distributed into CSF in adults and pediatric patients; CSF concentrations generally higher in patients with inflamed meninges than in those with uninflamed meninges.

Oral inhalation via nebulization: Sputum concentrations exhibit considerable interindividual variation; accumulation does not occur following multiple doses.

Crosses the placenta and is distributed into amniotic fluid.

Distributed into milk in low concentrations.

Plasma Protein Binding

46–60% bound to serum proteins in healthy adults at serum concentrations of 1–100 mcg/mL.

Adults with impaired renal function and decreased serum albumin concentrations: 22–49% bound to serum proteins.

Elimination

Metabolism

Partially metabolized to several microbiologically inactive metabolites; no active metabolites have been found in serum or urine.

Elimination Route

Eliminated principally in urine as unchanged drug via both glomerular filtration and tubular secretion. Partially excreted in feces, presumably via biliary elimination.

IM or IV: Approximately 58–74% of a dose excreted in urine unchanged, 1–7% excreted as SQ 26,992 (an inactive metabolite), and 3–4% excreted as unidentified inactive metabolites. Urinary excretion of unchanged drug essentially complete 8–12 hours after single dose, but SQ 26,992 excreted for up to 48 hours after the dose.

IV: Approximately 1% of single dose excreted in feces unchanged, 3% as SQ 26,992, and 7.5–10.8% as unidentified inactive metabolites.

Oral inhalation via nebulization: Approximately 10% of total dose excreted unchanged in urine; glomerular filtration and tubular secretion equally involved.

Removed by hemodialysis. Removed to a lesser extent by peritoneal dialysis.

Half-life

Adults with normal renal and hepatic function: Distribution half-life averages 0.2–0.7 hours and elimination half-life averages 1.3–2.2 hours.

Children 2 months to 12 years of age: Elimination half-life averages 1.7 hours.

Neonates: Half-life is longer than in older children and adults and is inversely related to age and birthweight. In neonates <7 days of age, elimination half-life averages 5.5–9.9 hours in those weighing <2.5 kg and 2.6 hours in those weighing >2.5 kg. In neonates 1 week to 1 month of age, elimination half-life averages 2.4 hours.

Oral inhalation via nebulization in adults with cystic fibrosis: Plasma elimination half-life of systemically absorbed drug is approximately 2.1 hours.

Special Populations

Geriatric adults: Elimination half-life is slightly longer than in younger adults and ranges from 1.7–4.3 hours in adults 64–82 years of age with renal function normal for their age.

Cystic fibrosis patients: May eliminate aztreonam at a faster rate than healthy individuals. Serum half-life averaged 1–1.3 hours in several patients with cystic fibrosis.

Patients with hepatic impairment: Half-life is only slightly prolonged since the liver is a minor elimination pathway for the drug. Elimination half-life in patients with cirrhosis but with normal renal function averages 2.2 hours in those with primary biliary cirrhosis and 3.2 hours in those with alcoholic cirrhosis.

Patients with renal impairment: Serum concentrations of aztreonam are higher and serum half-life prolonged. In adults with renal impairment, elimination half-life averages 3.4–3.6, 5.3–5.9, 7.8–7.9, or 8.4–8.7 hours in adults with Clcr of 30–80, 10–29, 3–9, or <2 mL/minute, respectively.

Stability

Storage

Parenteral

Powder for IV or IM Use

Room temperature (20–25°C); avoid excessive heat.

At a concentration of ≤20 mg/mL, aztreonam is chemically and physically stable for 48 hours at 15–30°C or for 7 days when refrigerated at 2–8°C in the following IV infusion solutions: 0.9% sodium chloride injection; 5 or 10% dextrose injection; Ringer’s; lactated Ringer’s; 5% dextrose and 0.2, 0.45, or 0.9% sodium chloride; 1/6 M sodium lactate; 5 or 10% mannitol; 5% dextrose with lactated Ringer’s; 5% dextrose with Plasma-Lyte M; Ionosol B with 5% dextrose; Isolyte E; Isolyte E with 5% dextrose; Isolyte M with 5% dextrose; Normosol-R; Normosol-R with 5% dextrose; or Normosol-M with 5% dextrose. At concentrations >20 mg/mL, aztreonam is stable for 48 hours at 2–8°C in sterile water for injection or 0.9% sodium chloride injection; solutions containing >20 mg/mL prepared using other compatible IV solutions should be used immediately.

IM solutions prepared using sterile water for injection or 0.9% sodium chloride injection are stable for 48 hours at 15–30°C or for 7 days when refrigerated at 2–8°C. IM injections prepared using bacteriostatic water for injection (with benzyl alcohol or parabens) or bacteriostatic sodium chloride injection (with benzyl alcohol or parabens) should be used immediately after reconstitution.

Injection (Frozen) for IV Infusion

−20° C or lower. After thawing, may store up to 48 hours at room temperature (25°C) or up to 14 days at 2–8° C.

Do not refreeze after thawing.

Powder for Inhalation Solution

Kit containing single-dose vials of lyophilized powder for inhalation solution and single-dose ampuls of diluent: 2–8°C. After removal from refrigerator, kit may be stored at room temperature (up to 25°C) for up to 28 days.

Protect lyophilized drug from light; do not use if stored at room temperature for longer than 28 days. Do not use diluent if it is cloudy or contains particles.

Use immediately following reconstitution.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1 253 HID

Compatible

Dextrose 5% in 0.2, 0.45, or 0.9% sodium chloride

Dextrose 5% in Ringer's injection, lactated

Dextrose 5 or 10% in water

Ionosol B with dextrose 5%

Isolyte E

Isolyte B, E, or M with dextrose 5%

Mannitol 5 or 10%

Normosol R

Normosol R or M with dextrose 5%

Plasma-Lyte M with dextrose 5%

Ringer's injection

Ringer's injection, lactated

Sodium chloride 0.9%

Sodium lactate 1/6 M

Drug Compatibility
Admixture CompatibilityHID

Compatible

Ampicillin sodium and sulbactam sodium

Cefazolin sodium

Ciprofloxacin

Clindamycin phosphate

Gentamicin sulfate

Linezolid

Tobramycin sulfate

Incompatible

Metronidazole

Nafcillin sodium

Variable

Ampicillin sodium

Cefoxitin sodium

Vancomycin HCl

Y-Site CompatibilityHID

Compatible

Allopurinol sodium

Amifostine

Amikacin sulfate

Aminophylline

Ampicillin sodium

Ampicillin sodium and sulbactam sodium

Bivalirudin

Bleomycin sulfate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Carboplatin

Carmustine

Caspofungin acetate

Cefazolin sodium

Cefotaxime sodium

Cefotetan disodium

Cefoxitin sodium

Ceftazidime

Ceftriaxone sodium

Cefuroxime sodium

Ciprofloxacin

Cisplatin

Clindamycin phosphate

Co-trimoxazole

Cyclophosphamide

Cytarabine

Dacarbazine

Dactinomycin

Daptomycin

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Docetaxel

Dopamine HCl

Doxorubicin HCl

Doxorubicin HCl liposomal

Doxycycline hyclate

Droperidol

Enalaprilat

Etoposide

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Filgrastim

Floxuridine

Fluconazole

Fludarabine phosphate

Fluorouracil

Foscarnet sodium

Furosemide

Gallium nitrate

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Idarubicin HCl

Ifosfamide

Imipenem and cilastatin sodium

Insulin, regular

Leucovorin calcium

Linezolid

Magnesium sulfate

Mannitol

Mechlorethamine HCl

Melphalan HCl

Meperidine HCl

Mesna

Methotrexate sodium

Methylprednisolone sodium succinate

Metoclopramide HCl

Morphine sulfate

Nalbuphine HCl

Nicardipine HCl

Ondansetron HCl

Pemetrexed disodium

Piperacillin sodium and tazobactam sodium

Potassium chloride

Promethazine HCl

Propofol

Quinupristin/dalfopristin

Ranitidine HCl

Remifentanil HCl

Sargramostim

Sodium bicarbonate

Teniposide

Theophylline

Thiotepa

Ticarcillin disodium and clavulanate potassium

Tigecycline

Tobramycin sulfate

Vinblastine sulfate

Vincristine sulfate

Vinorelbine tartrate

Zidovudine

Incompatible

Acyclovir sodium

Amphotericin B

Amphotericin B cholesteryl sulfate complex

Amsacrine

Azithromycin

Chlorpromazine HCl

Daunorubicin HCl

Ganciclovir sodium

Lansoprazole

Lorazepam

Oritavancin diphosphate

Metronidazole

Mitomycin

Mitoxantrone HCl

Prochlorperazine edisylate

Streptozocin

Variable

Vancomycin HCl

Actions and Spectrum

  • Monobactam antibiotic. Unlike other currently available β-lactam antibiotics, which are bicyclic and contain an adjoining ring fused to the β-lactam ring (e.g., carbapenems, cephalosporins, cephamycins, penicillins), monobactams are monocyclic β-lactam antibiotics.

  • Usually bactericidal, but not as rapidly bactericidal as some other β-lactam antibiotics (e.g., imipenem, cefotaxime, cefoxitin, ceftriaxone).

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.

  • Narrow spectrum of activity. Active against many gram-negative aerobic bacteria, but has little or no activity against gram-positive aerobic bacteria or anaerobic bacteria. Inactive against Chlamydia, Mycoplasma, fungi, and viruses.

  • Gram-negative aerobes: Active in vitro and in clinical infections against Citrobacter (including C. freundii), Enterobacter (including E. cloacae), Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains), Klebsiella oxytoca, K. pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. Also active in vitro against Aeromonas hydrophila, Moraxella catarrhalis (including β-lactamase-producing strains), Morganella morganii, Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Providencia rettgeri, P. stuartii, Serratia marcescens, Salmonella, Shigella, and Yersinia enterocolitica.

  • Inactive against Alcaligenes, Bordetella bronchiseptica, Brucella melitensis, Burkholderia (including B. cepacia, B. cenocepacia, B. gladioli, B. multivorans), Flavobacterium meningosepticum, Legionella pneumophila, and Stenotrophomonas maltophilia.

  • Gram-positive aerobes: May be active against some strains of Streptococcus pyogenes (group A β-hemolytic streptococci, GAS) and groups C and G streptococci, but most are resistant. S. agalactiae (group B streptococci, GBS), viridans streptococci, nonenterococcal group D streptococci, enterococci, Staphylococcus aureus, S. epidermidis, S. saprophyticus, Listeria monocytogenes, and Nocardia are resistant.

  • Anaerobes: Not active against most gram-positive and -negative anaerobes, including Clostridium perfringens, C. difficile, Eubacterium, Peptococcus, Peptostreptococcus, Fusobacterium, Veillonella, Bacteroides fragilis, and Prevotella melaninogenica.

Advice to Patients

  • Advise patients that antibacterials (including aztreonam) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

  • Importance of completing full course of therapy, even if feeling better after a few days.

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with aztreonam or other antibacterials in the future.

  • Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.

  • Advise patients that diarrhea is a common problem caused by systemic anti-infectives and usually ends when the drug is discontinued. Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as ≥2 months after the last dose.

  • Oral inhalation via nebulization: Advise patients to reconstitute the powder for inhalation solution using only the diluent provided by the manufacturer and to administer reconstituted solution only with the Altera nebulizer system.

  • Oral inhalation via nebulization: Advise patients to complete the full 28-day oral inhalation regimen, even if feeling better; if a dose is missed, advise patient to take all 3 daily doses as long as the doses are at least 4 hours apart.

  • Oral inhalation via nebulization: Advise patients to inform their clinician if they have new or worsening symptoms and to immediately contact a clinician if possible allergic reaction occurs.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Aztreonam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Kit

Aztreonam 75 mg powder for inhalation solution for nebulization

0.17% sodium chloride diluent

Cayston

Gilead

Parenteral

For injection

500 mg*

Aztreonam for Injection

1 g*

Azactam

Squibb

Aztreonam for Injection

2 g*

Azactam

Squibb

Aztreonam for Injection

Aztreonam in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (frozen), for IV infusion

20 mg/mL (1 g) in 3.4% Dextrose

Azactam in Iso-osmotic Dextrose Injection (Galaxy [Baxter])

Squibb

40 mg/mL (2 g) in 1.4% Dextrose

Azactam in Iso-osmotic Dextrose Injection (Galaxy [Baxter])

Squibb

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 7, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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