Ceftazidime Dosing in Adults with Severe Gram-Negative Infections and Renal Impairment
For severe Gram-negative infections in adults with impaired renal function, ceftazidime requires mandatory dose reduction based on creatinine clearance, with a loading dose of 1 gram followed by adjusted maintenance dosing: 1 gram every 12 hours for CrCl 31-50 mL/min, 1 gram every 24 hours for CrCl 16-30 mL/min, 500 mg every 24 hours for CrCl 6-15 mL/min, and 500 mg every 48 hours for CrCl <5 mL/min. 1
Standard Dosing for Normal Renal Function
For adults with normal renal function (CrCl >50 mL/min), the dosing varies by infection severity: 1
- Serious infections (complicated UTI, pneumonia, skin/soft tissue): 500 mg to 1 gram IV every 8 hours 1
- Severe life-threatening infections (including immunocompromised patients, meningitis, serious intra-abdominal/gynecologic infections): 2 grams IV every 8 hours 1
- Pseudomonas lung infections in cystic fibrosis: 30-50 mg/kg IV every 8 hours (maximum 6 grams/day) 1
Renal Dose Adjustment Algorithm
Critical principle: Ceftazidime is excreted almost exclusively by glomerular filtration, making dose reduction essential in renal impairment to prevent drug accumulation and neurotoxicity. 1, 2
Step-by-Step Dosing Approach:
Administer loading dose: Give 1 gram IV regardless of renal function 1
Calculate creatinine clearance using Cockcroft-Gault equation: 1
- Males: CrCl = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
- Females: 0.85 × male value
Apply maintenance dosing based on CrCl: 1
- CrCl 31-50 mL/min: 1 gram every 12 hours
- CrCl 16-30 mL/min: 1 gram every 24 hours
- CrCl 6-15 mL/min: 500 mg every 24 hours
- CrCl <5 mL/min: 500 mg every 48 hours
Important caveat: If the standard dose for the infection type (from Table 3 in FDA labeling) is lower than the renal-adjusted dose, use the lower dose 1
Dialysis Considerations
- Hemodialysis patients: Give 1 gram loading dose, then 1 gram after each dialysis session 1
- Peritoneal dialysis/CAPD: Give 1 gram loading dose, then 500 mg every 24 hours; can incorporate 250 mg per 2L of dialysis fluid 1
- Ceftazidime is removed by both hemodialysis and peritoneal dialysis, necessitating post-dialysis supplementation 1, 2
Modern Context: Ceftazidime-Avibactam Preferred for Resistant Organisms
While traditional ceftazidime remains effective for susceptible Gram-negative bacteria 2, 3, 4, current guidelines strongly favor newer agents for multidrug-resistant organisms: 5
For Carbapenem-Resistant Enterobacterales (CRE):
- First-line: Ceftazidime-avibactam 2.5 g IV every 8 hours (over 2-3 hours) 6, 7
- Alternatives: Meropenem-vaborbactam or imipenem-cilastatin-relebactam 5, 7
Ceftazidime-Avibactam Renal Dosing:
For CrCl >50 mL/min: 2.5 g every 8 hours; dose reductions required for moderate-severe renal impairment per FDA labeling to prevent neurotoxicity 6
Special Scenario - MBL-Producing Organisms:
Combination therapy with ceftazidime-avibactam plus aztreonam is strongly recommended for metallo-β-lactamase producers, as avibactam does not inhibit class B enzymes 5, 7
Critical Safety Monitoring
- Neurotoxicity risk: Monitor for seizures, encephalopathy, and confusion, particularly in renal impairment where beta-lactam accumulation occurs 6
- Therapeutic drug monitoring: Consider in severe infections with renal dysfunction 1
- Duration: Continue for 2 days after clinical resolution; complicated infections may require longer courses 1
Key Clinical Pitfalls to Avoid
- Never skip the loading dose in renal impairment—it ensures rapid therapeutic levels 1
- Avoid using traditional ceftazidime monotherapy for suspected CRE—resistance rates are high and newer agents show superior outcomes 5
- Do not use standard dosing in dialysis patients—ceftazidime is significantly removed during dialysis sessions 1
- Extended infusions (3 hours) may be necessary for severe infections or augmented renal clearance to optimize PK/PD targets 5, 8