Ceftolozane with tazobactam

SCOPE: §4.2 is COMPLETE in the bundle (no truncation marker) and the three regimens above are every indication in its Table 1, so no licensed adult regimen has been omitted. VERBATIM §4.2 Table 1 (intravenous dose of Zerbaxa by type of infection in adult patients (18 years or older) with creatinine clearance greater than 50 mL/min): 'Complicated intra-abdominal infection** 1 g ceftolozane / 0.5 g tazobactam, Every 8 hours, 1 hour, 4-14 days'; 'Complicated urinary tract infection / Acute pyelonephritis 1 g ceftolozane / 0.5 g tazobactam, Every 8 hours, 1 hour, 7 days'; 'Hospital-acquired pneumonia, including ventilator-associated pneumonia*** 2 g ceftolozane / 1 g tazobactam, Every 8 hours, 1 hour, 8-14 days'. The footnotes are dosing-relevant: creatinine clearance is estimated using the Cockcroft-Gault formula; complicated intra-abdominal infection is '**To be used in combination with metronidazole when anaerobic pathogens are suspected'; hospital-acquired/ventilator-associated pneumonia is '***To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.' NO MAXIMUM DOSE is populated for adults: the SPC gives a per-indication dose table, not an adult ceiling. The 2 g / 1 g pneumonia dose is the highest licensed adult regimen but it is that indication's dose and must NOT be applied to intra-abdominal or urinary infection, where the dose is 1 g / 0.5 g. The label's only explicit maximum is the PAEDIATRIC one (1 g ceftolozane / 0.5 g tazobactam per dose), which is recorded in paedDose. ELDERLY (65 years or older): 'No dose adjustment is necessary for the elderly based on age alone.' HEPATIC IMPAIRMENT: 'No dose adjustment is necessary in patients with hepatic impairment.' RENAL IMPAIRMENT: see renalAdjustment — the dose is reduced at creatinine clearance of 50 mL/min or below and differs between the pneumonia and the non-pneumonia indications. §4.4 warns that in trials of complicated intra-abdominal and complicated urinary tract infection, efficacy was lower in adult patients with moderate renal impairment than in those with normal or mildly impaired renal function at baseline; a decline in renal function has been seen in adults receiving ceftolozane/tazobactam.

dosePerKg refers to the CEFTOLOZANE component and is a PER-DOSE figure given every 8 hours, not a daily total — the matching tazobactam dose is 10 mg/kg per dose. VERBATIM §4.2 Table 2 (intravenous dose of Zerbaxa by type of infection in paediatric patients (from birth* to below 18 years of age) with eGFR** greater than 50 mL/min/1.73 m2): complicated intra-abdominal infection*** — '20 mg/kg ceftolozane / 10 mg/kg tazobactam up to a maximum dose of 1 g ceftolozane / 0.5 g tazobactam****', every 8 hours, 1 hour infusion, 5-14 days*****; complicated urinary tract infection / acute pyelonephritis — '20 mg/kg ceftolozane / 10 mg/kg tazobactam up to a maximum dose of 1 g ceftolozane / 0.5 g tazobactam****', every 8 hours, 1 hour infusion, 7-14 days*****. Footnotes, verbatim: '*Defined as > 32 weeks gestational age and ≥ 7 days postnatal.' '**eGFR estimated using Bedside Schwartz equation.' '***To be used in combination with metronidazole when anaerobic pathogens are suspected.' '****Children weighing > 50 kg should not exceed the maximum dose of 1 g ceftolozane / 0.5 g tazobactam.' '*****The total treatment duration shown may include intravenous Zerbaxa followed by appropriate oral therapy.' THE WEIGHT CEILING BINDS AT 50 kg: at and above 50 kg the dose is the fixed 1 g / 0.5 g, not 20 mg/kg. NOT LICENSED IN CHILDREN FOR PNEUMONIA, verbatim: 'The safety and efficacy of ceftolozane/tazobactam in children and adolescents below 18 years of age have not yet been established for the treatment of hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).' PAEDIATRIC RENAL IMPAIRMENT — NO REGIMEN EXISTS, verbatim: 'There is insufficient information to recommend a dose regimen for paediatric patients with moderate or severe renal impairment (eGFR ≤ 50 mL/min/1.73 m2) or end stage renal disease.' No concentration is populated: this is a powder for concentrate reconstituted and diluted per §6.6, which is not in this bundle. Verify the paediatric regimen against a children's formulary before use.