Background Ceftolozane/tazobactam is a novel antibiotic commonly used in infections by gram-negative bacteria resistant to conventional antibiotics. Drug-dosing errors are common in patients with renal impairment and can cause adverse effects or poor outcomes.
Purpose To determine the adequacy of ceftolozane/tazobactam dose adjustment according to renal function in hospitalised patients.
Material and methods Retrospective observational study in a third-level hospital involving patients treated with ceftolozane/tazobactam from January to August 2018. Variables collected: sex, age, creatinine clearance (CrCl), medical/critical care unit, type of infection, microorganisms isolated, type of therapy (empiric or targeted), posology, treatment duration, effectiveness of treatment (microbiological and/or clinical cure) and dosage adequacy. Underdosing was defined as any dose lower than the Summary of Product Characteristics recommended dose (based on CrCl) and overdosing was the opposite. For pneumonia (off-label), a double dose was considered according to the Stanford Health Care Antimicrobial Dosing Reference Guide.
Results Forty-six patients were included: 65.2% were male, mean age was 65.4±16.2 years and mean CrCl was 61.8±30.6 mL/min. At the beginning of treatment, 41.3% had CrCl <60 mL/min. Sixteen patients (34.8%) were admitted to the intensive care unit. Main infection sites were: respiratory (43.5%), urinary (30.4%) and intra-abdominal (15.2%). Therapy was basically targeted (73.9%) and the most common isolated pathogen was multidrug-resistant Pseudomonas aeruginosa (90.9%). Average treatment duration was 8.4 days.
Evaluation at first day of therapy showed that 29 patients (63.0%) received an inappropriate dosage, 18 (39.1%) were underdosed and 11 (23.9%) were overdosed. During treatment, 16 patients experienced a change in CrCl but dose was not adjusted accordingly in the majority of cases (n=10, 62.5%).
Patients with empiric treatment had a favourable evolution. Among patients with targeted therapy and respiratory, urinary or intra-abdominal infection (n=30) treatment was effective in 23 (76.7%). Ceftolozane/tazobactam was de-escalated in two (6.7%), changed by another antibiotic because of inefficacy in two (6.7%) and discontinued because of poor prognosis in three (10.0%).
Conclusion A considerable proportion of patients treated with ceftolozane/tazobactam were inappropriately dosed. Furthermore, dosage was not adapted to the changes in renal function throughout the treatment. These data highlight the importance of an adequate review of medication.
References and/or acknowledgements No conflict of interest.
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