About This Calculator

The Ceftolozane-Tazobactam Dose Calculator is a clinical support tool designed for healthcare professionals. It helps determine the appropriate intravenous (IV) dosage of ceftolozane-tazobactam (Zerbaxa®) based on the patient’s specific indication and renal function. Dosing is adjusted according to creatinine clearance (CrCl), which the tool can estimate using the Cockcroft-Gault equation.

This tool is intended for educational and informational purposes and should not replace clinical judgment, institutional protocols, or professional medical advice.

Outputs Explained

After processing the inputs, the calculator provides the following key outputs:

• Recommended Dose: The precise dose of ceftolozane-tazobactam and the dosing frequency (e.g., 1.5 g IV every 8 hours). For patients on hemodialysis, this may include both a loading and maintenance dose.
• Calculation Basis: A summary of the key parameters used for the calculation, such as the patient’s indication (cUTI/cIAI or HAP/VAP) and their estimated or manually entered creatinine clearance.
• Clinical Notes: Important context-specific information, such as administration advice for patients on hemodialysis or warnings for severe renal impairment.

How to Use the Calculator

To ensure accurate dose calculation, follow these steps:

1. Select Indication: Choose the appropriate indication for treatment: “Complicated UTI / Intra-abdominal Infection” or “Hospital/Ventilator-Acquired Pneumonia.”
2. Enter Patient Data: For automatic CrCl calculation, input the patient’s age (years), weight (kg or lbs), sex, and serum creatinine (mg/dL or µmol/L). The tool uses the Cockcroft-Gault formula for this estimation.
3. Use Overrides (If Applicable):
   • Check “Manually Enter Creatinine Clearance” to input a known CrCl value directly. This will disable the patient data fields.
   • Check “End-Stage Renal Disease on Hemodialysis (HD)” or “Continuous Renal Replacement Therapy (CRRT)” for specific dosing recommendations for these populations.
4. Calculate: Click the “Calculate Dose” button to view the results. Use the “Reset” button to clear all fields for a new calculation.

Dosing Overview

Ceftolozane-tazobactam dosing is dependent on both the infection being treated and the patient’s renal function. The dose for HAP/VAP is higher than for cUTI/cIAI. As renal function declines (lower CrCl), the dose and/or frequency is reduced to prevent drug accumulation and potential toxicity.

Renal Dose Adjustments (IV every 8 hours)

Switching Therapy

Ceftolozane-tazobactam is an intravenous antibiotic used for serious infections. Decisions regarding switching to an alternative IV or oral antibiotic (de-escalation) should be based on clinical response, microbiological culture and susceptibility results, and infectious diseases consultation. This calculator does not provide guidance on switching therapies.

Missed Dose

In a hospital setting, if a scheduled dose of ceftolozane-tazobactam is missed, it should be administered as soon as it is remembered. The subsequent doses should be adjusted to maintain the correct dosing interval from the time the missed dose was given. Do not administer two doses at once to make up for a missed dose. Always follow institutional protocols for managing missed medication administrations.

Safety Alerts

Use of ceftolozane-tazobactam requires careful consideration of the following:

• Decreased Efficacy in Renal Impairment: In a clinical trial for cIAI, clinical cure rates were lower in patients with a baseline CrCl of 30 to 50 mL/min. Monitor renal function closely during treatment.
• Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported with beta-lactam antibacterials. Inquire about previous hypersensitivity to cephalosporins, penicillins, or other beta-lactams before initiating therapy.
• Clostridioides difficile-Associated Diarrhea (CDAD): CDAD has been reported with nearly all systemic antibacterial agents and may range in severity from mild diarrhea to fatal colitis.

Frequently Asked Questions

Why does the calculator require age, weight, and sex?

These demographic data points are necessary variables for the Cockcroft-Gault equation, which the calculator uses to estimate creatinine clearance (CrCl), a key indicator of renal function for drug dosing.

How does the dosing for HAP/VAP differ from cUTI/cIAI?

The recommended dose for Hospital-Acquired and Ventilator-Acquired Pneumonia (HAP/VAP) is double the dose for Complicated Urinary Tract and Intra-abdominal Infections (cUTI/cIAI) across all levels of renal function, reflecting the severity and nature of the infection.

How does the calculator handle patients on hemodialysis (HD)?

For patients with End-Stage Renal Disease (ESRD) on HD, the tool provides a one-time loading dose followed by a significantly reduced maintenance dose administered every 8 hours. The prescribing information notes that doses should be administered after the HD session on dialysis days.

What guidance is provided for patients on CRRT?

The tool recognizes that dosing for patients on Continuous Renal Replacement Therapy (CRRT) is complex and highly dependent on the specific CRRT modality and effluent rate. It advises consulting institutional protocols or a clinical pharmacist, as a standard recommendation cannot be provided.

Can I use this calculator for pediatric patients?

No. The safety and effectiveness of ceftolozane-tazobactam in patients under 18 years of age have not been established. The Cockcroft-Gault equation is also intended for use in adults.

What weight should be used for obese patients?

The calculator uses the actual body weight entered. The use of ideal, adjusted, or actual body weight in the Cockcroft-Gault equation for obese patients is a matter of clinical debate. Clinicians should use their judgment and consider institutional guidelines when dosing obese patients.

What happens if a patient’s CrCl is less than 15 mL/min but they are not on dialysis?

The calculator indicates that dosing recommendations for this specific patient population have not been established in clinical trials. Treatment should be approached with caution and ideally with specialist consultation.

Does the calculator account for Augmented Renal Clearance (ARC)?

No, the tool does not specifically account for ARC (e.g., CrCl > 130 mL/min). In such cases, standard dosing for normal renal function (CrCl > 50 mL/min) is recommended, but therapeutic drug monitoring should be considered if available and clinically indicated.

References

1. ZERBAXA® (ceftolozane and tazobactam) Prescribing Information. U.S. Food and Drug Administration. Revised: 06/2019.
2. Merck & Co., Inc. ZERBAXA Product Information for Healthcare Professionals. Accessed October 2023.
3. Tumbarello M, Viale P, Bassetti M, et al. A review of ceftolozane/tazobactam for the treatment of complicated urinary tract and intra-abdominal infections. Infection and Drug Resistance. 2016;9:63-74. doi:10.2147/IDR.S86035.
4. Kollef MH, Nováček M, Kivistik Ü, et al. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. The Lancet Infectious Diseases. 2019;19(12):1299-1311. doi:10.1016/S1473-3099(19)30403-7.