β lactam antibiotic
Binds to penicillin binding protein (transpeptidase) and
prevents crosslinking of bacterial peptidoglycan
impairs cell wall synthesis

Bacteriocidal antimicrobials that block DNA replication by blocking tropoisomerase enzymes, which are essential for the supercoiling, replication and separation of circular bacterial DNA

Poorly absorbed orally
Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.

Good oral absorption (80%)

Undergoes first pass

Coadministration of calcium or magnesium reduces absorption

Widely distributed in body tissues and fluids.

Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low

High CSF and tissue penetration

30% PB

30% PB

Vd <1L/kg

Vd 2-3L/kg

Piperacillin is not metabolized in man.

Tazobactam is mainly metabolized to M1, an inactive metabolite.

Little hepatic metabolism

Renal: 80% unchanged + metabolite

Active tubular secretion

Half-life of Piperacillin-tazobactam: 0.7 to 1.2 hours

T1/2= 3 hours (renal dose adjustment required)

1. Hypokalaemia (lower sodium concentration so hypernatraemia less likely)
2. Piptaz + vancomycin associated with increased AKI
3. LFT derangement
Neutropenia

1. CNS Toxicity- GABA antagonists and may precipitate seizures in epileptic patients, particularly in presence of NSAIDs
2. Tendonitis and tendon rupture
3. QT prolongation- Low risk of Torsade’s in absence of other predisposing factors
4. Hemolysis in G6PD
5. Photosensitivity
6. Arthralgias and cartilage toxicity (generally avoided in children)
7. Dysglycaemia (hyper and hypoglycaemia)

Pseudomonas
Beta-lactamase producing bacteria
Gram negatives
Anaerobes

Broad spectrum
Active against both gram positive and gram negative bacteria

particularly effective against
GNB (E.Coli, H.influenza, Klebsiella, Legionella, Moraxella, Proteus, and Pseudomonas)
Less effective against Gram-positive bacteria (such as MSSA, Strep pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones

ANTIBIOTIC:
PENICILLIN

ANTIBIOTIC:
QUINOLONE

used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes.
E.g: cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections.

Antipseudomonal penicillin

Quinolone

Level 1

Level 3

Level 1

PO and IV, topical eye drops and ointment

Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance

Alteration in target enzyme – changes to the DNA binding surface of DNA supergyrase infers resistance
Alteration in drug entry – altered expression of outer membrane porin proteins that form channels for passive diffusion of ciprofloxacin
Increase in efflux of drug – expression of nonspecific energy dependent efflux pumps which remove drug

Removed by haemodialysis