Ceftolozane-tazobactam: Difference between revisions
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==Background== |
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*Novel antipseudomonal antibiotic |
*Novel antipseudomonal antibiotic |
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===Mechanism of Action=== |
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*Structure is similar to [[ceftazidime]], but with C3 substitution |
*Structure is similar to [[ceftazidime]], but with C3 substitution |
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*[[Ceftolozane]] is stable against AmpC β-lactamases and is somewhat resistant to efflux pumps and |
*[[Ceftolozane]] is stable against AmpC β-lactamases and is somewhat resistant to efflux pumps and |
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*[[Tazobactam]] is active against most class A and some class C β-lactamases |
*[[Tazobactam]] is active against most class A and some class C β-lactamases |
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*Bactericidal |
*Bactericidal |
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===Acitivity=== |
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*GNB: |
*GNB: |
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*Variable against anaerobes |
*Variable against anaerobes |
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===Pharmacokinetics and Pharmacodynamics=== |
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=== PK/PD === |
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*Half-life about 2.5 hours |
*Half-life about 2.5 hours |
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*No significant drug-drug interactions |
*No significant drug-drug interactions |
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== Dosing == |
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* Urinary tract and intraabdominal infection: ceftolozane-tazobactam 1.5 g (1 g / 0.5 g) IV q8h |
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* Pneumonia: ceftolozane-tazobactam 3 g IV q8h |
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==Safety== |
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*Adverse events similar to other cephalosporins |
*Adverse events similar to other cephalosporins |
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*GI effects, [[Clostridioides difficile]], liver enzymes |
*GI effects, [[Clostridioides difficile]], liver enzymes |
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==Evidence== |
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*ASPECT-cIAI: complicated intraabdo infections with metronidazole |
*ASPECT-cIAI: complicated intraabdo infections with metronidazole |
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Revision as of 13:38, 12 September 2020
Background
- Novel antipseudomonal antibiotic
Mechanism of Action
- Structure is similar to ceftazidime, but with C3 substitution
- Ceftolozane is stable against AmpC β-lactamases and is somewhat resistant to efflux pumps and
- Tazobactam is active against most class A and some class C β-lactamases
- Bactericidal
Acitivity
- GNB:
- MDRPsA with less affinity for Pseudomonal AmpC and less affected by efflux and porins
- Enterobacterales, including many ESBLs
- Activity against AmpC organisms is variable (50% for Enterobacter vs 97% for Escherichia coli)
- Not active against carbapenemase-producing organisms
- Limited activity against Oxa-48
- Limited activity against Acinetobacter species and Stenotrophomonas maltophilia
- GPC: possibly active against Strep pneumo and pyogenes, but none against Staph and Enterococcus
- Variable against anaerobes
Pharmacokinetics and Pharmacodynamics
- Half-life about 2.5 hours
- Protein binding 20%
- Good penetration into lung
- Renally cleared
- No significant drug-drug interactions
Dosing
- Urinary tract and intraabdominal infection: ceftolozane-tazobactam 1.5 g (1 g / 0.5 g) IV q8h
- Pneumonia: ceftolozane-tazobactam 3 g IV q8h
Safety
- Adverse events similar to other cephalosporins
- GI effects, Clostridioides difficile, liver enzymes
Evidence
- ASPECT-cIAI: complicated intraabdo infections with metronidazole
- Solomkin CID 2015;60:1462-1471
- Compared to meropenem
- ASPECT-cUTI: complicated UTI
- Wagenlehner Lancet 2015;385:1949-1956
- Compared to levofloxacin
- ASPECT-NP: nosocomial pneumonia
- Kolleff Lancet ID 2019;19:1299
- Compared to meropenem
