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.

Crosses BBB with CSF conc = 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.

partially hepatic

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

highly protein bound and is able to displace bilirubin from albumin binding sites,
causing bilirubin; should be avoided in jaundiced neonates.
Pseudolithiasis or Biliary sludge due to a precipitate of Calcium-ceftriaxone seen occasionally.

May cause injection site irritation. May cause seizures similar to Benpen but only in
susceptible patients. Caution in renal patients due to large amount excreted
unchanged. Should not be used concurrenly with probenecid. Can cause
confusion

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)

ANTIBIOTIC:
CEPHALOSPORIN

ANTIBIOTIC:
CARBAPENEM

used for the
treatment of infections caused by susceptible Gram-positive and Gram-negative bacteria, including infections of the abdomen, bones and joints, CNS, skin and skin
structures, genito-urinary tract (including gonorrhoea), respiratory tract, gynaecological infections, Lyme disease.

broader spectrum of action than other beta lactams
used in serious infections only
Unlike other carbapenems Meropenems do not require coadministration with cilastatin because
it is not degraded by renal dipeptidase

3rd Generation Cephalosporin

Carbapenem (contain a fused beta-lactam & a -5-member ring system that differs from penicillins
because it is unsaturated and contains a carbon instead of a sulphur atom)

Level 1

Level 1

1g daily (2g BD for meningitis)

White powder for IV-
yellowish solution.
Can precipitate with Ca2+ containing solutions

IV: White crystals for reconstitution- 500mg or 1gm.
Very expensive

cephalosporinases hydrolyse β-lactam rings.
PBP modification.
Enterobacter: Change in porins – Impermeable.

Carbapenemases Metallobetalactamases
(Sternotrophomonas)
Efflux pumps.
Pseudomonas: Change PBP, diminish permeability thru porin modification

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

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

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