Ceftolozane-tazobactam: Difference between revisions
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==Background== |
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*Antipseudomonal antibiotic |
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*Novel antipseudomonal antibiotic |
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===Mechanism of Action=== |
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*Structure is similar to [[ceftazidime]], but with C3 substitution |
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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 |
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===Acitivity=== |
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*GNB: |
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**MDRPsA with less affinity for pseudomonal AmpC and less affected by efflux and porins |
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**Enterobacterales, including many ESBLs |
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***Activity against AmpC organisms is variable (50% for [[Enterobacter]] vs 97% for [[Escherichia coli]]) |
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**Not active against carbapenemase-producing organisms |
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**Limited activity against Oxa-48 |
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**Limited activity against [[Acinetobacter]] and [[Stenotrophomonas maltophilia]] |
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*GPC: possibly active against Strep pneumo and pyogenes, but none against Staph and Enterococcus |
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*Variable against anaerobes |
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===Pharmacokinetics and Pharmacodynamics=== |
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*Half-life about 2.5 hours |
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*Protein binding 20% |
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*Good penetration into lung |
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*Renally cleared |
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*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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*Multi-drug-resistant [[Pseudomonas aeruginosa]]: |
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**[[Cystitis]]: 1.5 g IV q8h infused over 1 h |
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**Other infections: 3 g IV q8h infused over 3 hours |
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==Safety== |
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*Adverse events similar to other cephalosporins |
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*GI effects, [[Clostridioides difficile]], liver enzymes |
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==Evidence== |
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*ASPECT-cIAI: complicated intraabdo infections with metronidazole |
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**Solomkin CID 2015;60:1462-1471 |
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**Compared to meropenem |
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*ASPECT-cUTI: complicated UTI |
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**Wagenlehner Lancet 2015;385:1949-1956 |
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**Compared to levofloxacin |
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*ASPECT-NP: nosocomial pneumonia |
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**Kolleff Lancet ID 2019;19:1299 |
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**Compared to meropenem |
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[[Category: |
[[Category:Cephalosporins]] |
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[[Category: |
[[Category:β-lactamase inhibitors]] |
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Latest revision as of 16:28, 28 January 2022
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 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
- Multi-drug-resistant Pseudomonas aeruginosa:
- Cystitis: 1.5 g IV q8h infused over 1 h
- Other infections: 3 g IV q8h infused over 3 hours
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
