Introduction

Antibacterial; monocyclic β-lactam antibiotic; monobactam.

Uses for Aztreonam

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.

Although aztreonam has good in vitro activity against many gram-negative bacteria, it has relatively poor activity against extended-spectrum β-lactamase (ESBL)-producing strains of E. coli and K. pneumoniae.

For the treatment of peritoneal dialysis-associated peritonitis, aztreonam has been administered [Web]^{† [off-label]}.

Gynecologic Infections

Treatment of gynecologic infections (e.g., endometritis, 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.

The combination of clindamycin and gentamicin has been the gold standard for treatment of endometritis; however, a regimen consisting of aztreonam plus clindamycin has been used.

Oral or topical antibiotics (e.g., clindamycin, metronidazole) are generally used for the treatment of other common gynecologic infections (e.g., bacterial vaginosis).

Respiratory Tract Infections

Treatment of lower respiratory tract infections (e.g., pneumonia, 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^{† [off-label]}, Hafnia^{† [off-label]}, K. oxytoca^{† [off-label]}, Morganella^{† [off-label]}, 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.

A joint guideline by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) includes aztreonam as an empiric treatment option for Ps. aeruginosa in adults with community-acquired pneumonia treated in the inpatient setting. The guideline recommends empiric coverage for Ps. aeruginosa only if locally validated risk factors for the pathogen are present.

In adults with hospital-acquired and ventilator-associated pneumonia, IDSA suggests aztreonam as an empiric treatment option for gram-negative/antipseudomonal coverage; if patient has a severe penicillin allergy and aztreonam is used instead of a β-lactam-based antibiotic, coverage for methicillin-sensitive S. aureus (MSSA) should be included.

Also has been used alone or in conjunction with an aminoglycoside for treatment of acute exacerbations of bronchopulmonary Ps. aeruginosa infections in some patients with cystic fibrosis.

Aztreonam for inhalation solution (Cayston) is used via nebulization to improve respiratory symptoms in cystic fibrosis patients ≥7 years of age with Ps. aeruginosa in the lungs. Safety and efficacy of this preparationnot 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^†.

The Surviving Sepsis Campaign guidelines recommend immediate administration of appropriate antimicrobials in adults with possible sepsis or septic shock. Empiric antimicrobials with adequate coverage should be selected based on patient’s risk for certain pathogens (e.g., MRSA, multidrug-resistant organisms).

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.

Aztreonam is not included as a potential antimicrobial of choice in IDSA guidelines on the management of skin and skin structure infections; when broad-spectrum empiric treatment is necessary for suspected polymicrobial infection, other antibiotics are generally recommended.

When empiric treatment of moderate or severe diabetic foot infections is indicated, IDSA recommends a broad-spectrum regimen pending results of in vitro culture and susceptibility testing. When probable pathogens include MRSA, Enterobacteriaceae, Pseudomonas, and obligate anaerobes, IDSA recommends an empiric regimen of vancomycin in conjunction with ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, or a carbapenem. If aztreonam, ceftazidime, or cefepime is used in conjunction with vancomycin, the empiric regimen should also include an additional anti-infective for anaerobic coverage.

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.

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.

CNS Infections

Treatment of healthcare-associated ventriculitis and meningitis^† caused by susceptible aerobic gram-negative bacteria in patients with anaphylaxis or other contraindications to β-lactam therapy (including carbapenems).

Has been effective for adults and children with meningitis due to Ps. aeruginosa, H. influenzae, and other Enterobacteriaceae.

IDSA guidelines suggest that choice between aztreonam and other alternatives (such as ciprofloxacin for Ps. aeruginosa or trimethoprim-sulfamethoxazole for β-lactamase-producing Enterobacteriacea) should consider local susceptibility patterns and known co-infecting organisms.

Antimicrobial Prophylaxis in Surgery

Antimicrobial 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^†.

An anti-infective active against staphylococci (e.g., vancomycin) also should be used if aztreonam is used for empiric therapy in these patients. Some guidelines have suggested a regimen of aztreonam and vancomycin as an alternative empiric regimen in patients with immediate-type penicillin hypersensitivity.

Aztreonam Dosage and Administration

Administration

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

Also administered by oral inhalation via nebulization using the commercially available powder for inhalation solution.

Has been administered intraperitoneally^† in dialysis fluid.

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 is 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.

Rate of Administration

Administer 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 patient condition. 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

Neonates ≤7 days of age^†: AAP recommends 30 mg/kg every 12 hours in those whose gestational age is <34 weeks or 30 mg/kg every 8 hours in those whose gestational age is ≥34 weeks.

Neonates 8–28 days of age^†: AAP recommends 30 mg/kg every 8 hours in those whose gestational age is <34 weeks or 30 mg/kg every 6 hours in those whose gestational age is ≥34 weeks.

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 90–120 mg/kg daily given in 3 or 4 divided doses.

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.

Intra-abdominal Infections

IV

30 mg/kg IV every 6–8 hours has been used in children >9 months of age. Higher doses may be reasonable in critically ill pediatric patients who may have an increased volume of distribution and/or accelerated clearance of antimicrobial agents.

Cystic Fibrosis Patients with Ps. Aeruginosa

Oral Inhalation via Nebulization

Children ≥7 years of age: 75 mg 3 times daily for 28 days. Administer 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

1 or 2 g every 8 or 12 hours.

Severe Systemic or Life-threatening Infections

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

Usual dosage 1–2 g IV every 8 hours. In patients with impaired renal function, an initial dose of 1–2 g IV followed by 0.5–1 g IV every 6–12 hours is usually given.

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. Administer 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 Cl_cr ≤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.

S_cr 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 Cl_cr.

Adults with Cl_cr 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 Cl_cr <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. One modeling study suggests that aztreonam 1 g (for MICs up to 4 mg/L) or 2 g (for MICs up to 8 mg/L) daily after hemodialysis would yield adequate concentrations.

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.

Contraindications

• Hypersensitivity to aztreonam or any component in the formulation.

Warnings/Precautions

Hypersensitivity

Immediate hypersensitivity reactions, including anaphylaxis, bronchospasm, generalized urticaria with or without palpebral and lingual edema and respiratory impairment, and shock, rash, and eosinophilia, reported with parenteral aztreonam. Toxic epidermal necrolysis reported rarely.

Rash reported with orally inhaled aztreonam. Allergic reactions with facial rash, facial swelling, and throat tightness also reported.

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

Prior to initiation of therapy, assess whether patient has had 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).

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.

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

Clostridioides difficile-associated Diarrhea and Colitis

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridiodes 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.

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.

Toxic Epidermal Necrolysis

Toxic epidermal necrolysis reported in a few patients undergoing bone marrow transplant; these patients had multiple risk factors including sepsis and radiation therapy, and were receiving other drugs associated with toxic epidermal necrolysis.

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 got empiric treatment of infections that may involve gram-positive bacteria or anaerobes (e.g., gynecologic, intra-abdominal, or respiratory tract infections).

Overgrowth of Nonsusceptible Organisms

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

Precautions Related to Oral Inhalation Therapy

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.

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.

Specific Populations

Pregnancy

No adequate and controlled studies to date in pregnant women. Do not use during pregnancy unless clearly needed.

Crosses placenta and enters fetal circulation.

Lactation

IV or IM: Low concentrations (<1%) distributed into milk. Consider temporarily discontinuing breast-feeding during aztreonam therapy.

Oral inhalation via nebulization: Peak plasma concentrations following 75-mg dose by oral inhalation via nebulization are approximately 1% of peak plasma concentrations following 500-mg IV dose. Systemic absorption following inhaled administration is likely minimal. Effects on the infant or on milk production are unknown.

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.

Renal Impairment

Monitor renal function. Adjust IV or IM dosage is adults based on degree of renal impairment.

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.

Administration

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

Also administered by oral inhalation via nebulization using the commercially available powder for inhalation solution.

Has been administered intraperitoneally^† in dialysis fluid.

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 is 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.

Rate of Administration

Administer 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 patient condition. 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

Neonates ≤7 days of age^†: AAP recommends 30 mg/kg every 12 hours in those whose gestational age is <34 weeks or 30 mg/kg every 8 hours in those whose gestational age is ≥34 weeks.

Neonates 8–28 days of age^†: AAP recommends 30 mg/kg every 8 hours in those whose gestational age is <34 weeks or 30 mg/kg every 6 hours in those whose gestational age is ≥34 weeks.

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 90–120 mg/kg daily given in 3 or 4 divided doses.

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.

Intra-abdominal Infections

IV

30 mg/kg IV every 6–8 hours has been used in children >9 months of age. Higher doses may be reasonable in critically ill pediatric patients who may have an increased volume of distribution and/or accelerated clearance of antimicrobial agents.

Cystic Fibrosis Patients with Ps. Aeruginosa

Oral Inhalation via Nebulization

Children ≥7 years of age: 75 mg 3 times daily for 28 days. Administer 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

1 or 2 g every 8 or 12 hours.

Severe Systemic or Life-threatening Infections

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

Usual dosage 1–2 g IV every 8 hours. In patients with impaired renal function, an initial dose of 1–2 g IV followed by 0.5–1 g IV every 6–12 hours is usually given.

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. Administer 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 Cl_cr ≤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.

S_cr 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 Cl_cr.

Adults with Cl_cr 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 Cl_cr <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. One modeling study suggests that aztreonam 1 g (for MICs up to 4 mg/L) or 2 g (for MICs up to 8 mg/L) daily after hemodialysis would yield adequate concentrations.

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.

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