Intra-abdominal infection, health care–associated or high-risk community-acquired infection (alternative agent):
Note: Reserve for patients who cannot use beta-lactams (eg, penicillins, cephalosporins, carbapenems). For community-acquired infection, reserve for severe infection or patients at high risk of adverse outcome and/or resistance (Barshak 2021; SIS/IDSA [Solomkin 2010]).
Cholecystitis, acute uncomplicated: IV: 1 to 2 g every 8 hours as part of an appropriate combination; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2021).
Other intra-abdominal infection (eg, cholangitis, complicated cholecystitis, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 1 to 2 g every 8 hours as part of an appropriate combination. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Gomi 2018; Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, total duration is 7 to 10 days (Barshak 2021; Pemberton 2021).
Meningitis, bacterial (community-acquired or health care-associated) (alternative agent) (off-label use): As a component of empiric therapy for health care-associated infection or pathogen-specific therapy (eg, H. influenzae (beta-lactamase positive), Enterobacteriaceae or P. aeruginosa): IV: 2 g every 6 to 8 hours; for empiric therapy, must be used in combination with other appropriate agents (IDSA [Tunkel 2004; Tunkel 2017]).
Osteomyelitis, native vertebral due to P. aeruginosa (off-label use): IV: 2 g every 8 hours for 6 weeks. Note: Double coverage may be considered (ie, aztreonam plus an aminoglycoside) (IDSA [Berbari 2015]).
Pneumonia (alternative agent for patients with severe penicillin allergy [eg, anaphylaxis]):
Community-acquired pneumonia: For empiric therapy of inpatients at risk of infection with a resistant gram-negative pathogen, including P. aeruginosa:
IV: 2 g every 8 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days, or for P. aeruginosa, 7 days. Patients should be clinically stable with normal vital signs before therapy is discontinued (ATS/IDSA [Metlay 2019]; File 2021).
Hospital-acquired or ventilator-associated pneumonia: IV: 2 g every 8 hours; when used for empiric therapy, give as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]).
Severe systemic or life-threatening infections (eg, Pseudomonas aeruginosa): IV: 2 g every 6 to 8 hours; maximum: 8 g/day. Note: Higher doses (8 to 12 g/day) may be needed for patients with cystic fibrosis (Zobell 2013).
Surgical (perioperative) prophylaxis (off-label use): IV: 2 g within 60 minutes prior to surgery. Doses may be repeated in 4 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013).
Urinary tract infection: IM, IV: 500 mg to 1 g every 8 to 12 hours; maximum: 8 g/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
|
CrClc (mL/minute) |
If the usual recommended dose is 1 g every 8 hours |
If the usual recommended dose is 2 g every 6 or 8 hours |
|---|---|---|
|
a Recommendations are expert opinion derived from: Fillastre 1985; Gerig 1984; Gross 2018; Mihindu 1983; Xu 2017; manufacturer's labeling. | ||
|
b Doses >1 g should be given IV. | ||
|
c Calculated using the Cockcroft-Gault equation. | ||
|
d A reduced dose while maintaining the frequency may be preferred in severe infections (Xu 2017), although maintaining the dose but prolonging the dosing interval has been described (Fillastre 1985; Mihindu 1983) and is utilized by some centers. | ||
|
e Dialyzable (~30% to 60% with low flux dialyzers [Fillastre 1985; Gerig 1984]); when scheduled dose falls on a dialysis day, administer after hemodialysis (Gross 2018). | ||
|
30 to <130 |
No dosage adjustment necessary |
No dosage adjustment necessary |
|
10 to <30d |
1 g every 12 hours or 1 g as a single dose then 500 mg every 8 hours |
2 g every 12 hours or 2 g as a single dose then 1 g every 6 or 8 hours |
|
<10d |
1 g every 24 hours or 1 g as a single dose then 250 mg every 8 hours |
2 g every 24 hours or 2 g as a single dose then 500 mg every 6 or 8 hours |
|
Hemodialysis, intermittent (thrice weekly)e |
1 g every 24 hours |
2 g every 24 hours |
|
Peritoneal dialysis |
1 g every 24 hours |
2 g every 24 hours |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
IV: If usual recommended dose is 2 g every 6 to 8 hours: 2 g every 6 hours (Xu 2017; expert opinion). Consider prolonging the infusion time to over 4 hours (Cies 2017; expert opinion).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: 2 g as a single dose followed by 1 g every 8 hours or 2 g every 12 hours (Heintz 2009; expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: 2 g as a single dose followed by 1 to 2 g every 12 hours. Ensure at least 1 dose is infused after PIRRT session ends on PIRRT days (expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution (minor hepatic elimination occurs).
(For additional information see "Aztreonam (systemic): Pediatric drug information")
General dosing, susceptible infection: Infants, Children, and Adolescents (Red Book [AAP 2015]):
Mild to moderate infection: IM, IV: 90 mg/kg/day in divided doses every 8 hours; maximum daily dose: 3,000 mg/day
Severe infection: IM, IV: 90 to 120 mg/kg/day in divided doses every 6 to 8 hours; maximum daily dose: 8 g/day
Cystic fibrosis (Pseudomonas aeruginosa) : Infants, Children, and Adolescents: IV: 150 to 200 mg/kg/day in divided doses every 6 to 8 hours (Kliegman 2016); higher doses have been used: 200 to 300 mg/kg/day divided every 6 hours; maximum daily dose: 12 g/day (Zobell 2012)
Intra-abdominal infections, complicated: Infants, Children, and Adolescents: IV: 90 to 120 mg/kg/day divided every 6 to 8 hours in combination with metronidazole; maximum dose: 2,000 mg (Solomkin 2010)
Peritonitis (peritoneal dialysis), treatment: Infants, Children, and Adolescents: Intraperitoneal: Continuous: Loading dose: 1,000 mg per liter of dialysate; maintenance dose: 250 mg per liter (ISPD [Warady 2012])
Surgical prophylaxis: Children and Adolescents: IV: 30 mg/kg within 60 minutes before procedure; may repeat in 4 hours for prolonged procedure or excessive blood loss; maximum dose: 2,000 mg (Bratzler 2013)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: IM, IV: The following adjustments have been recommended (Aronoff 2007). Note: Renally adjusted dose recommendations are based on doses of 90 to 120 mg/kg/day divided every 8 hours.
GFR ≥30 mL/minute/1.73 m2: No adjustment required
GFR 10-29 mL/minute/1.73 m2: 15 to 20 mg/kg every 8 hours
GFR <10 mL/minute/1.73 m2: 7.5 to 10 mg/kg every 12 hours
Intermittent hemodialysis: 7.5 to 10 mg/kg every 12 hours
Peritoneal dialysis (PD): 7.5 to 10 mg/kg every 12 hours
Continuous renal replacement therapy (CRRT): No adjustment required.
There are no dosage adjustments provided in manufacturer’s labeling. Use with caution (minor hepatic elimination occurs).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Azactam in Dextrose: 1 g/50 mL (50 mL [DSC]); 2 g/50 mL (50 mL [DSC]) [sodium free]
Solution Reconstituted, Injection [preservative free]:
Azactam: 1 g (1 ea); 2 g (1 ea) [sodium free]
Generic: 1 g (1 ea); 2 g (1 ea)
May be product dependent
Injection: Doses >1 g should be administered IV.
IM: Administer by deep injection into large muscle mass, such as upper outer quadrant of gluteus maximus or the lateral part of the thigh.
IV: Administer by slow IV push over 3 to 5 minutes or by intermittent infusion over 20 to 60 minutes. For extended infusion administration (off-label method), administer over 3 (Tennant 2015; Thompson 2016) or 4 hours (Cies 2017).
Parenteral:
IV: IV route is preferred for doses >1,000 mg or in patients with severe life-threatening infections. Administer by IVP over 3 to 5 minutes or by intermittent infusion over 20 to 60 minute.
IM: Administer by deep IM injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh. Doses >1,000 mg should be administered IV. Do not mix with any local anesthetic agent.
Treatment of patients with urinary tract infections, lower respiratory tract infections, septicemia, skin/skin structure infections, intra-abdominal infections, and gynecological infections caused by susceptible gram-negative bacilli
Meningitis, bacterial; Osteomyelitis, native vertebral; Surgical prophylaxis (perioperative)
Aztreonam may be confused with azidothymidine
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Hematologic & oncologic: Neutropenia (children 3% to 11%; adults <1%)
Hepatic: Increased serum transaminases (children, high dose: >3 times ULN: 15% to 20%; children, standard dose: increased serum AST 4%, increased serum ALT 7%)
Local: Pain at injection site (children 12%, adults 2%)
1% to 10%:
Cardiovascular: Phlebitis (intravenous: ≤2%), thrombophlebitis (intravenous: ≤2%)
Dermatologic: Skin rash (children 4%, adults ≤1%)
Gastrointestinal: Diarrhea (≤1%), nausea (≤1%), vomiting (≤1%)
Hematologic & oncologic: Eosinophilia (children 6%, adults <1%), thrombocythemia (children 4%, adults <1%)
Local: Erythema at injection site (intravenous: Children 3%, adults <1%), discomfort at injection site (intramuscular: ≤2%), swelling at injection site (intramuscular: ≤2%)
Renal: Increased serum creatinine (children 6%)
Miscellaneous: Fever (≤1%)
<1%, postmarketing, and/or case reports: Abdominal cramps, anaphylaxis, anemia, angioedema, breast tenderness, bronchospasm, chest pain, Clostridioides difficile–associated diarrhea, confusion, diaphoresis, diplopia, dizziness, dysgeusia, dyspnea, erythema multiforme, exfoliative dermatitis, flushing, gastrointestinal hemorrhage, halitosis, headache, hepatitis, hepatobiliary disease, hypotension, increased serum alkaline phosphatase, increased serum ALT (adults), increased serum AST (adults), induration at injection site, insomnia, jaundice, leukocytosis, malaise, myalgia, nasal congestion, numbness of tongue, oral mucosa ulcer, pancytopenia, paresthesia, petechia, positive direct Coombs test, prolonged partial thromboplastin time, prolonged prothrombin time, pruritus, pseudomembranous colitis, purpura, seizure, sneezing, thrombocytopenia, tinnitus, toxic epidermal necrolysis, urticaria, vaginitis, ventricular bigeminy (transient), ventricular premature contractions (transient), vertigo, vulvovaginal candidiasis, weakness, wheezing
Hypersensitivity to aztreonam or any component of the formulation
Concerns related to adverse effects:
• Beta-lactam allergy: Rare cross-allergenicity to penicillins, cephalosporins, or carbapenems may occur; use with caution in patients with a history of hypersensitivity to beta-lactams.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosing adjustment required.
Special populations:
• Bone marrow transplantation: Use with caution in patients undergoing bone marrow transplant with multiple risk factors for toxic epidermal necrolysis (TEN) (eg, sepsis, radiation therapy, drugs known to cause TEN); rare cases of TEN in this population have been reported.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Aztreonam crosses the placenta and can be detected in the fetus.
Information related to aztreonam for the treatment of urinary tract infections in pregnancy is limited. Use may be considered in pregnant patients allergic to preferred antibiotics (Glaser 2015; Jolley 2010).
Aztreonam is present in breast milk in concentrations <1% of the corresponding maternal serum concentration. In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora (WHO 2002). The poor oral absorption of aztreonam from the gastrointestinal tract (<1%) (Clark 1992) may limit adverse effects to the infant.
Periodic renal and hepatic function tests; monitor for signs of anaphylaxis during first dose
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Monobactam structure makes cross-allergenicity with beta-lactams unlikely.
Absorption: IM: Well absorbed; IM and IV doses produce comparable serum concentrations.
Distribution: Widely into body tissues, cerebrospinal fluid, bronchial secretions, peritoneal fluid, bile, and bone.
Vd: Neonates: 0.26 to 0.36 L/kg; Children: 0.2 to 0.29 L/kg; Adults: 0.15 to 0.18 L/kg (Brogden 1986).
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs).
CSF:blood level ratio: Meninges: Inflamed: 8% to 40%; Normal: ~1%.
Protein binding: 56%.
Metabolism: Hepatic (minor %).
Half-life elimination:
Neonates: <7 days of age, <2.5 kg: 5.71 ± 1.63 hours; <7 days of age, >2.5 kg: 2.56 ± 0.2 hours; 1 week to 1 month of age: 2.43 ± 0.35 hours (Stutman 1984).
Infants and children <12 years of age: ~1.7 ± 0.2 hours (Stutman 1984).
Children with cystic fibrosis: 1.3 hours.
Adults: Normal renal function: 1.5 to 2 hours.
End-stage renal disease: 6 to 8.4 hours (Brogden 1986).
Time to peak: IM: Within 60 minutes (Mattie 1988).
Excretion: Urine (60% to 70% as unchanged drug); feces (~12%).
Altered kidney function: Serum half-life is prolonged.
Anti-infective considerations:
Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC) and AUC24 to MIC ratio:
Organism specific:
Gram-negative organisms (eg, E. coli, P. aeruginosa): Goal: 50% to 60% fT > MIC (bacteriostatic); ≥65% fT > MIC (bactericidal) (Crandon 2013; Ramsey 2016).
Expected drug exposure in normal renal function:
Pediatric patients: Cmax (peak): 30 mg/kg (3-minute infusion), single dose: IV:
Neonates <1 week of age, <2.5 kg: 83 ± 21.3 mg/L (Stutman 1984).
Neonates <1 week of age, >2.5 kg: 97.8 ± 5 mg/L (Stutman 1984).
Neonates ≥1 week to 1 month of age: 97.4 ± 4.3 mg/L (Stutman 1984).
Infants and children ≤2 years of age: 118.7 ± 6.7 mg/L (Stutman 1984).
Children >2 to 12 years of age: 96.9 ± 16.2 mg/L (Stutman 1984).
Adults: Cmax (peak): Single dose (30-minute infusion): IV:
500 mg: 54 mg/L.
1 g: 90 mg/L.
2 g: 204 mg/L.
Postantibiotic effect: Generally little to no postantibiotic effect (<1 hour) for gram-negative bacilli (including P. aeruginosa) (Hanberger 1990; Ramsey 2016).
Solution (reconstituted) (Azactam Injection)
1 g (per each): $34.80
2 g (per each): $69.60
Solution (reconstituted) (Aztreonam Injection)
1 g (per each): $32.77 - $43.30
2 g (per each): $65.54 - $87.97
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