Ceftolozane + Tazobactam
Indications
Ceftolozane + Tazobactam is used for:
Complicated Intra-abdominal Infections
Adult Dose
Complicated Intra-abdominal Infections
Indicated for use in combination with metronidazole for complicated intra-abdominal infections (cIAI) cause by Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius
1.5 g IV q8hr x4-14 days
Complicated Urinary Tract Infections
Indicated for complicated urinary tract infections (cUTI), including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa
1.5 g IV q8hr x7 days
Bacterial Pneumonia
Indicated for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens
3 g IV q8hr x8-14 days
Child Dose
<18 years: Safety and efficacy not established
Renal Dose
Renal impairment
cIAI or cUTI
CrCl 30-50 mL/min: 750 mg (500 mg/250 mg) IV q8hr
CrCl 15-29 mL/min: 375 mg (250 mg/125 mg) IV q8hr
ESRD on hemodialysis: Administer a single loading dose of 750 mg (500 mg/250 mg) followed by a 150-mg (100 mg/50 mg) maintenance dose administered q8hr for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis)
HABP/VABP
CrCl 30-50 mL/min: 1.5 g (1 g/0.5 g) IV q8hr
CrCl 15-29 mL/min: 750 mg (500 mg/250 mg) IV q8hr
ESRD on hemodialysis: Administer a single loading dose of 2.25 g (1.5 g/0.75 g) followed by a 450-mg (300 mg/150 mg) maintenance dose administered q8hr for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following dialysis completion)
Administration
IV Preparation
Reconstitute vial with 10 mL of sterile water for injection or 10 mL 0.9% NaCl and gently shake to dissolve
Final volume is ~11.4 mL
Must be further diluted; reconstituted solution is NOT for direct injection
Withdraw appropriate volume for dose and add to 100 mL of 0.9% NaCl or D5W
Inspect for particulate matter and discoloration; color ranges from clear, colorless solutions to solutions that are clear and slightly yellow
Dose volume
3 g (2 g/1 g): 2 vials of 11.4 mL each (entire contents from 2 vials)
2.25 g (1.5 g/0.5 g): 11.4 mL from 1 vial (entire contents) and 5.7 mL from a second vial
1.5 g (1 g/0.5 g): 11.4 mL (entire vial contents)
750 mg (500 mg/250 mg): 5.7 mL
450 mg (300 mg/150 mg): 3.5 mL
375 mg (250 mg/125 mg): 2.9 mL
150 mg (100 mg/50 mg): 1.2 mL
IV Administration
Infuse IV over 1 hr
Contra Indications
Hypersensitivity to any of the components
Precautions
Clinical cure rates lower in patients with baseline CrCl of 30 to ≤50 mL/min when compared with other antibiotics in clinical trials
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions reported with beta-lactam antibacterial agents
As with all antibiotics, Clostridium difficile-associated diarrhea (CDAD) has been reported; if suspected, discontinue and initiate prompt treatment for CDAD
Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria
Pregnancy-Lactation
Pregnancy
There are no data available on ceftolozane/tazobactam or its individual components regarding use in pregnant women to assess drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes
Human data: Although available studies with multiple cephalosporins cannot definitively establish absence of risk, published data from prospective cohort studies, case series, and case reports over several decades have not identified an association of cephalosporin use during pregnancy with major birth defects, miscarriage, or other adverse maternal or fetal outcomes
Lactation
There are no data on presence of either drug component in human milk; there are no data on effects of either drug component on breastfed infant, or on milk production
Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal conditions
Interactions
Adverse Effects
Side effects of Ceftolozane + Tazobactam :
>10% (HABP/VABP)
Increased hepatic transaminase (11.9%)
1-10% (cIAI or cUTI)
Nausea (2.8-7.9%)
Headache (2.5-5.8%)
Diarrhea (1.9-6.2%)
Pyrexia (1.7-5.6%)
Constipation (1.9-3.9%)
Insomnia (1.3-3.5%)
Vomiting (1.1-3.3%)
Hypokalemia (0.8-3.3%)
ALT increased (1.7-1.5%)
AST increased (1-1.7%)
Anemia (0.4-1.5%)
Thrombocytosis (0.4-1.9%)
Abdominal pain (0.8-1.2%)
Anxiety (0.2-1.9%)
Dizziness (0.8-1.1%)
Hypotension (0.4-1.7%)
Atrial fibrillation (0.2-1.2%)
Rash (0.9-1.7%)
1-10% (HABP/VABP)
Renal impairment/failure (8.9%)
Diarrhea (6.4%)
Intracranial hemorrhage (4.4%)
Vomiting (3.3%)
Clostridium difficile colitis (2.8%)
Mechanism of Action
Ceftolozane: Cephalosporin that has demonstrated potent in vitro activity against Pseudomonas aeruginosa
Tazobactam: Beta-lactamase inhibitor