Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and
prevents crosslinking of bacterial peptidoglycan
inhibits cell wall synthesis
BROADER SPECTRUM

Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested

Configuration: Stability against Betalactamases

Binds to several penicillin binding protein and
prevents crosslinking of bacterial peptidoglycan
inhibits cell wall synthesis
BROADEST SPECTRUM

Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested

Configuration: Stability against Betalactamases and ESBLs

Well absorbed when given IM
IV/IM
Dose is 1-2g daily or BD
On/dur serum peak in 2-3hrs (IM)

IV route only
Dose is 500mg-1g TDS
On/dur peak at 1hr

Crosses the BBB, improved with inflam

Hydrophilic with a small volume of distribution (~0.3 L/kg). Penetrates CSF, particularly with inflamed meninges. CSF concentrations are variable and lower than plasma.

85 – 95% PB
Highly protein bound, non-linear dose response

2% PB
Minimally protein bound

small Vd 0.5L/kg

small Vd 0.3 L/kg

minimally hepatic

Minimal metabolism, mainly non-hepatic hydrolysis to an inactive metabolite. Hepatic impairment has little effect on meropenem pharmacokinetics.

excreted mostly unchanged in urine and
bile

excreted in urine 70% unchanged

half life 8 hours enabling daily dosing

half life 1-1.5 hrs
renal failure significantly increases half life

Bacteriocidal

Active against:
- GP cocci (including pen resistant pneumococcus), sensitive staph
- Extended G-ve cover (aerobes)- enterobacter resistance is rapid
- Inferior anaerobe cover compared to second generation

* ESCAPPMs can induce resistance so treatment failures can occur

v.broad spectrum, gram positive, gram
negative (incl pseudomonal) and anaerobic
coverage (resistant to beta lactamases and
cephalosporinases)

1g daily (2g BD for meningitis)

PK changes in Critical Illness:
----------------

D:
Vd ↑’s in critical illness
loading dose (LD = Vd x desired concentration) may increase
Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs

Protien binding - albumin is generally reduced in critical illness → ↑ Ceftriaxone plasma conc → ↓ dose

M:
minimal change due to lack of metabolism

E:
excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose should not exceed 2gm/day)

Protein binding of ceftriaxone reduces CRRT clearance (nil dose adjustment required)

PK changes in Critical Illness:
----------------

D:
Vd ↑’s in critical illness
loading dose (LD = Vd x desired concentration) may increase
Meropenem is a hydrophilic beta-lactam and Vd may increase in critical illness

M:
minimal change due to lack of metabolism

E:
excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose reduction required)
Low protein binding → Meropenem is cleared via CRRT →↑dose freq