Ceftolozane-tazobactam: Difference between revisions

Revision as of 13:24, 26 August 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

PK/PD

Half-life about 2.5 hours
Protein binding 20%
Good penetration into lung
Renally cleared
No significant drug-drug interactions

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 ==
-*Antipseudomonal antibiotic
-*[[Ceftolozane]] is stable against AmpC β-lactamases and is somewhat resistant to efflux
+*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
+=== PK/PD ===
+*Half-life about 2.5 hours
+*Protein binding 20%
+*Good penetration into lung
+*Renally cleared
+*No significant drug-drug interactions
+=== 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
 [[Category:Antibiotics]]