What is the appropriate use and dosage of Ceftolizine for an adult patient?

Ceftolozane/Tazobactam: Appropriate Use and Dosage for Adult Patients

Ceftolozane/tazobactam is indicated for critically ill adults with healthcare-associated intra-abdominal infections or hospital-acquired pneumonia when multidrug-resistant Pseudomonas aeruginosa or ESBL-producing organisms are suspected, dosed at 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) intravenously every 8 hours, or 3 g every 8 hours for pneumonia. 1

Primary Indications

Healthcare-Associated Intra-Abdominal Infections

• For critically ill patients with healthcare-associated IAI, ceftolozane/tazobactam 1.5 g IV every 8 hours plus metronidazole 500 mg every 6 hours is recommended as a carbapenem-sparing regimen. 1
• This regimen is specifically indicated when patients have recent antibiotic exposure, reside in nursing homes with indwelling catheters, or have post-operative IAI. 1
• Vancomycin 25-30 mg/kg loading dose then 15-20 mg/kg every 8 hours must be added for enterococcal coverage. 1

Difficult-to-Treat Pseudomonas Aeruginosa Infections

• For any clinical syndrome caused by difficult-to-treat P. aeruginosa (DTR-PA), ceftolozane/tazobactam 1.5-3 g IV every 8 hours is recommended. 1
• The 3 g dose (2 g ceftolozane/1 g tazobactam) infused over 1 hour every 8 hours is specifically indicated for hospital-acquired or ventilator-associated pneumonia. 1
• Treatment duration is 5-10 days for complicated UTI and complicated intra-abdominal infection, and 10-14 days for hospital-acquired pneumonia and bloodstream infection. 1

Mechanism and Spectrum of Activity

• Ceftolozane's chemical structure is similar to ceftazidime but with a modified side-chain at the 3-position of the cephem nucleus, conferring potent antipseudomonal activity. 2
• The drug evades multiple P. aeruginosa resistance mechanisms including efflux pumps, reduced porin uptake, and PBP modification, making it active against carbapenem-resistant, piperacillin/tazobactam-resistant, and ceftazidime-resistant strains. 2
• Tazobactam extends activity to include most ESBL-producing Enterobacteriaceae and some anaerobic species. 2

Pharmacokinetics and Dosing Considerations

• Ceftolozane demonstrates linear pharmacokinetics with a mean plasma half-life of 2.3 hours, steady-state volume of distribution of 13.1-17.6 L, and low plasma protein binding (20%). 2
• Dose adjustment is required for creatinine clearance <50 mL/min. 2
• The drug is primarily eliminated via urinary excretion (≥92%), and the pharmacokinetic-pharmacodynamic index correlating with efficacy is %fT>MIC. 2

Critical Combination Requirements

For Intra-Abdominal Infections

• Metronidazole 500 mg IV every 6 hours must be added to ceftolozane/tazobactam for adequate anaerobic coverage in IAI. 1
• For patients at high risk for invasive candidiasis, add echinocandins (caspofungin 70 mg loading dose then 50 mg daily, anidulafungin 200 mg loading dose then 100 mg daily, or micafungin 100 mg daily). 1

For Suspected MDR Pseudomonas

• In patients with suspected or proven infection with MDR (non-metallo-beta-lactamase-producing) P. aeruginosa, consider antibiotic combinations with ceftolozane/tazobactam. 1

Important Caveats and Limitations

• Ceftolozane/tazobactam has no activity against metallo-beta-lactamase-producing organisms or carbapenemase-producing Klebsiella pneumoniae (use ceftazidime/avibactam instead). 1
• The drug has limited activity against anaerobes such as Bacteroides fragilis, necessitating metronidazole co-administration for polymicrobial infections. 2
• For documented beta-lactam allergy, consider antibiotic combinations with amikacin 15-20 mg/kg every 24 hours instead. 1

Treatment Duration and Monitoring

• Treatment duration should be individualized based on infection site, source control, underlying comorbidities, and initial response to therapy. 1
• For complicated UTI and IAI: 5-10 days. 1
• For hospital-acquired pneumonia and bloodstream infection: 10-14 days. 1
• Clinical response should guide continuation rather than predetermined protocols. 1