Ceftolozane-tazobactam: Difference between revisions
From IDWiki
No edit summary |
m (Text replacement - " species]]" to "]]") |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
| − | == |
+ | ==Background== |
*Novel antipseudomonal antibiotic |
*Novel antipseudomonal antibiotic |
||
| − | === |
+ | ===Mechanism of Action=== |
*Structure is similar to [[ceftazidime]], but with C3 substitution |
*Structure is similar to [[ceftazidime]], but with C3 substitution |
||
| − | *[[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 |
*[[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 |
||
*Bactericidal |
*Bactericidal |
||
| − | === |
+ | ===Acitivity=== |
*GNB: |
*GNB: |
||
| − | **MDRPsA with less affinity for |
+ | **MDRPsA with less affinity for pseudomonal AmpC and less affected by efflux and porins |
**Enterobacterales, including many ESBLs |
**Enterobacterales, including many ESBLs |
||
***Activity against AmpC organisms is variable (50% for [[Enterobacter]] vs 97% for [[Escherichia coli]]) |
***Activity against AmpC organisms is variable (50% for [[Enterobacter]] vs 97% for [[Escherichia coli]]) |
||
**Not active against carbapenemase-producing organisms |
**Not active against carbapenemase-producing organisms |
||
**Limited activity against Oxa-48 |
**Limited activity against Oxa-48 |
||
| − | **Limited activity against [[Acinetobacter |
+ | **Limited activity against [[Acinetobacter]] and [[Stenotrophomonas maltophilia]] |
*GPC: possibly active against Strep pneumo and pyogenes, but none against Staph and Enterococcus |
*GPC: possibly active against Strep pneumo and pyogenes, but none against Staph and Enterococcus |
||
*Variable against anaerobes |
*Variable against anaerobes |
||
| + | ===Pharmacokinetics and Pharmacodynamics=== |
||
| − | === PK/PD === |
||
*Half-life about 2.5 hours |
*Half-life about 2.5 hours |
||
| Line 30: | Line 30: | ||
*No significant drug-drug interactions |
*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 |
*Adverse events similar to other cephalosporins |
||
*GI effects, [[Clostridioides difficile]], liver enzymes |
*GI effects, [[Clostridioides difficile]], liver enzymes |
||
| − | == |
+ | ==Evidence== |
*ASPECT-cIAI: complicated intraabdo infections with metronidazole |
*ASPECT-cIAI: complicated intraabdo infections with metronidazole |
||
| Line 47: | Line 55: | ||
**Compared to meropenem |
**Compared to meropenem |
||
| − | [[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
