ceftolozane/tazobactam

Ceftolozane: binds to bacterial cell wall membrane, causing cell death. Spectrum is extended compared with other penicillins. Tazobactam: Inhibits beta-lactamase, an enzyme that can destroy penicillins.

Therapeutic effects:

Death of susceptible bacteria.

Spectrum:

Active against Bacteroides fragilis, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcesens, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Ceftolozane: minimal metabolism, excreted almost entirely (>95%) unchanged in urine; tazobactam: 80% excreted unchanged in urine, some metabolized to an inactive M1 metabolite which is excreted unchanged in urine.

Half-Life: Ceftolozane: 2.8 hr; tazobactam: 0.9 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Known serious hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam or other beta-lactams;
Pedi: eGFR 50 mL/min/1.73 m2.

Use Cautiously in:

CCr 30–<50 mL/min (effectiveness may be ↓ in adults);
CCr <50 mL/min (dose adjustment recommended in adults);
OB: Use during pregnancy only if potential benefit outweighs potential risks;
Lactation: Use cautiously if breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

CV: atrial fibrillation, hypotension

Derm: rash

F and E: hypokalemia

GI: diarrhea, abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, nausea, vomiting

Hemat: anemia, thrombocytosis

Neuro: anxiety, dizziness, headache, insomnia

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Complicated Intra-abdominal Infections or Complication Urinary Tract Infections

IV (Adults ): 1.5 g (1 g ceftolozane/0.5 g tazobactam) every 8 hr for 4–14 days for complicated intra-abdominal infection or 7 days for complicated urinary tract infection.
IV (Children <18 yr and eGFR >50 mL/min/1.73 m²): 30 mg/kg (max dose = 1.5 g) every 8 hr for 5–14 days for complicated intra-abdominal infection or 7–14 days for complicated urinary tract infection.

Renal Impairment

(Adults ): CCr 30–50 mL/min: 750 mg (500 mg ceftolozane/250 mg tazobactam) every 8 hr; CCr 15–29 mL/min: 375 mg (250 mg ceftolozane/125 mg tazobactam) every 8 hr; End-stage renal disease on hemodialysis: Single loading dose of 750 mg (500 mg ceftolozane/250 mg tazobactam), then 150 mg (100 mg ceftolozane/50 mg tazobactam) every 8 hr (on dialysis days administer as soon as possible after dialysis).

Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia

IV (Adults ): 3 g (2 g ceftolozane/1 g tazobactam) every 8 hr for 8–14 days.

Renal Impairment

(Adults ): CCr 30–50 mL/min: 1.5 g (1 g ceftolozane/0.5 g tazobactam) every 8 hr; CCr 15–29 mL/min: 750 mg (500 mg ceftolozane/250 mg tazobactam) every 8 hr; End-stage renal disease on hemodialysis: Single loading dose of 2.25 g (1.5 g ceftolozane/0.75 g tazobactam), then 450 mg (300 mg ceftolozane/150 mg tazobactam) every 8 hr (on dialysis days administer as soon as possible after dialysis).

Availability ⬆ ⬇

Powder for injection: 1 g ceftolozane/0.5 g tazobactam/vial

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
Before initiating therapy, obtain a history to determine previous use of and reactions to penicillins, cephalosporins, or other beta-lactams. Persons with a negative history of sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several mo following cessation of therapy.

Lab Test Considerations:

Monitor CCr at least daily in patients with changing renal function and adjust dose accordingly.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute with 10 mL of sterile water for injection or 0.9% NaCl for injection; shake gently to dissolve for final volume of 11.4 mL.Diluent: Withdraw 11.4 mL for 1.5 g (1.0 g/0.5 g dose, 5.7 mL for 750 mg (500 mg/250 mg) dose, 2.9 mL for 375 mg (250 mg/125 mg) dose, or 1.2 mL for 150 mg (100 mg/50 mg) dose and add to 100 mL of 0.9% NaCl or D5W. Solution is clear, colorless to slightly yellow; do not administer solutions that are discolored or contain particulate matter. Solution is stable for 24 hr at room temperature or 7 days if refrigerated; do not freeze.
Rate: Infuse over 1 hr.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of ceftolozane/tazobactam to patient.
Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇