Ceftolozane-tazobactam: Difference between revisions

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

@@ Line 1: / Line 1: @@
-== Background ==
+==Background==
 *Novel antipseudomonal antibiotic
-=== Mechanism of Action ===
+===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 ===
+===Acitivity===
 *GNB:
-**MDRPsA with less affinity for Pseudomonal AmpC and less affected by efflux and porins
+**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]]
+**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===
-=== PK/PD ===
 *Half-life about 2.5 hours
@@ Line 30: / Line 30: @@
 *No significant drug-drug interactions
-=== Safety ===
+==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 ===
+==Evidence==
 *ASPECT-cIAI: complicated intraabdo infections with metronidazole