What are the dosing and infusion guidelines for ceftazidime (Ceftazidime)/sulbactam and aztreonam (Aztreonam) in patients with impaired renal function?

Dosing and Infusion Guidelines for Ceftazidime and Aztreonam

Standard Dosing for Normal Renal Function

For adults with normal renal function, administer ceftazidime 1-2 grams IV every 8-12 hours and aztreonam 1-2 grams IV every 8 hours, with higher doses (ceftazidime 2g every 8 hours; aztreonam 2g every 6-8 hours) reserved for severe infections, Pseudomonas aeruginosa, or life-threatening conditions. 1, 2

Ceftazidime Dosing by Infection Severity

• Uncomplicated UTI: 250 mg IV/IM every 12 hours 2
• Complicated UTI: 500 mg IV/IM every 8-12 hours 2
• Uncomplicated pneumonia or mild skin infections: 500 mg to 1 gram IV/IM every 8 hours 2
• Serious infections (gynecologic, intra-abdominal, bone/joint): 2 grams IV every 8-12 hours 2
• Meningitis or life-threatening infections: 2 grams IV every 8 hours 2
• Pseudomonas in cystic fibrosis: 30-50 mg/kg IV every 8 hours (maximum 6 grams/day) 2

Aztreonam Dosing by Infection Severity

• UTI: 500 mg or 1 gram IV/IM every 8-12 hours 1
• Moderately severe systemic infections: 1-2 grams IV/IM every 8-12 hours 1
• Severe or life-threatening infections: 2 grams IV every 6-8 hours 1
• Pseudomonas aeruginosa infections: 2 grams every 6-8 hours recommended at initiation 1

Dosing in Renal Impairment

Ceftazidime Renal Dosing

Give an initial loading dose of 1 gram, then adjust maintenance doses based on creatinine clearance (CrCl). 2

• CrCl 50-31 mL/min: 1 gram every 12 hours 2
• CrCl 30-16 mL/min: 1 gram every 24 hours 2
• CrCl 15-6 mL/min: 500 mg every 24 hours 2
• CrCl <5 mL/min: 500 mg every 48 hours 2
• Hemodialysis: 1 gram loading dose, then 1 gram after each dialysis session 2
• Peritoneal dialysis: 1 gram loading dose, then 500 mg every 24 hours (can add 250 mg per 2L dialysis fluid) 2

The terminal half-life of ceftazidime increases from 1.57 hours in normal subjects to approximately 25 hours in severely uremic patients. 3

Aztreonam Renal Dosing

Give the usual initial dose (500 mg, 1g, or 2g), then reduce maintenance doses by 50% for moderate impairment and 75% for severe impairment. 1

• CrCl 10-30 mL/min: Give half the usual dose at usual intervals (every 6,8, or 12 hours) 1
• CrCl <10 mL/min or hemodialysis: Give one-fourth the usual dose at usual intervals, plus one-eighth the initial dose after each hemodialysis 1

Administration and Infusion Techniques

Standard Infusion

• Ceftazidime: Can be given as IV bolus over 3-5 minutes or as intermittent infusion 2, 3
• Aztreonam: IV route recommended for doses >1 gram or severe infections; can be given IM for smaller doses 1

Extended/Prolonged Infusions for Severe Infections

For critically ill patients or infections with high-MIC organisms (MIC ≥4 mg/L), consider extended infusions of 3-4 hours or continuous infusion to optimize time above MIC. 4

• Extended infusions improve pharmacodynamic target attainment, particularly for Pseudomonas infections 4
• For cefepime (similar β-lactam), continuous infusion has shown independent protective effects in sepsis; this principle applies to ceftazidime 4

Combination Therapy: Ceftazidime-Avibactam Plus Aztreonam

For metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE), the combination of ceftazidime-avibactam plus aztreonam is the preferred treatment, showing significantly lower 30-day mortality. 5, 6

• This combination demonstrates synergy against NDM and VIM producers 5
• Ceftazidime does not interfere with aztreonam/avibactam activity—MICs remain within one 2-fold dilution regardless of ceftazidime concentration 7
• Dosing: Standard doses of both agents (ceftazidime-avibactam 2.5g every 8 hours + aztreonam 2g every 8 hours) 6
• Prolonged infusion (3 hours) of ceftazidime-avibactam improves 30-day survival 6

Duration of Therapy

Continue treatment for at least 48 hours after the patient becomes asymptomatic or bacterial eradication is documented. 1, 2

• Mild-moderate infections: 5-7 days when clinical stability achieved 6
• Severe infections: Minimum 7-14 days 6
• Complicated infections: May require several weeks 1
• Immunocompromised patients: Longer courses often necessary 6

Pediatric Dosing

Ceftazidime

• Neonates (0-4 weeks): 30 mg/kg IV every 12 hours 2
• Infants and children (1 month-12 years): 30-50 mg/kg IV every 8 hours (maximum 6 grams/day) 2
• Severe infections/immunocompromised/meningitis: Use higher end of dosing range 2

Aztreonam

• Mild-moderate infections: 30 mg/kg every 8 hours 1
• Moderate-severe infections: 30 mg/kg every 6-8 hours 1
• Maximum recommended dose: 120 mg/kg/day 1

Critical Pitfalls and Monitoring

• Avoid intramuscular administration for doses >1 gram or in severe infections (septicemia, abscess, peritonitis) 1
• Monitor renal function closely in elderly patients—serum creatinine may not accurately reflect renal status; calculate CrCl using Cockcroft-Gault equation 1, 2
• Therapeutic drug monitoring should be considered in critically ill patients with fluctuating renal function 4
• Do not use ceftazidime or aztreonam for Acinetobacter infections—intrinsic resistance renders them ineffective 5
• Cross-reactivity warning: Avoid aztreonam in patients with immediate-type allergy to ceftazidime or cefiderocol due to shared side-chain structures 8
• In patients with coagulation concerns receiving cefoperazone-sulbactam combinations, vitamin K supplementation reduces bleeding risk 9