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]] |
| − | [[Category: |
+ | [[Category:β-lactamase inhibitors]] |
Latest revision as of 12:28, 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
