Contains a beta lactam ring structure. Betalactam antibiotics inhibit the growth of sensitive bacteria by inactivating transpeptidase enzymes located in the bacterial cell membrane, inhibiting crosslinkage of peptidoglycans and thus impairing cell wall synthesis

bactericidal

Binds to the bacterial 30S ribosomal subunit to inhibit protein synthesis and thus bacterial growth

Inhibits Glycopeptide synthetase  prevents peptidoglycan formation in bacterial cell well
(Unlike penicillins, prevents the transfer and addition of the muramylpentapeptide
building blocks that make up the peptidoglycan molecule itself.)
May also alter membrane permeability and selectively inhibit RNA synthesis.
Antimicrobial activity Dependent on Duration above MIC, not concentration

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

BA 62%

BA no oral absorption, rapid and complete IM.
IV (poor lipid solubility)
doses 3-10mcg/kg depending on severity
onset / duration 30mins

bioavailabilty Oral: Poor; I.M.: Erratic; Intraperitoneal: ~38%
IV. dose loading 20mg/kg then 1-1.5g daily based on levels

Good oral absorption (80%)

Undergoes first pass

Coadministration of calcium or magnesium reduces absorption

penetration into CSF occurs with inflamed meninges only

lip sol low - reduces gut absorption
some CSF penetration with inflamed meninges (30%)

Distributes widely in
body tissue and fluids, except for CSF, improved CSF penetration with inflamed meninges

High CSF and tissue penetration

20% PB

<30% PB

~50% PB

30% PB

Vd 0.2-0.3 L/kg

Vd: 0.4-1 L/kg

Vd 2-3L/kg

Some Hepatic Metabolism

not metabolised

Little or no metabolism

Little hepatic metabolism

Mostly unchanged in urine.
Rest is feces and bile

excretion urine as unchanged drug

excretion via kidneys unchanged
Not effectively removed by dialysis

Active tubular secretion

half life 1.5-3 hrs, +++ in renal impairment (up to 70hrs)

half life Biphasic half life, prolonged in renal fail. Mean t1/2 4-6hrs

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

ototoxicity
nephrotoxicity (worse with loop diuretics or pre-existing renal disease)
pre-jn Ach release   post-jn sensitivity to Ach NMBD activity can cause paralysis.

May cause C.Diff.

Hypersensitivity reactions including anaphylaxis.
Rapid infusion is associated with histamine release - red-man syndrome.
Ototoxicity rare, dose related. Nephrotoxicity has declined with improved formulations, usually resolves with cessation of drug

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)

Moderate spectrum
Semisynthetic
Can penetrate some gram
negative outer membranes,
but susceptible to betalactamases. Often given with clauvanic acid
Targets
Strep, Listeria, Enterococcus, Haemophilus

provide good gram negative coverage and some gram positive
most often used against enteric infections and in sepsis
usually used in combination with a beta lactam

active against most gram positive bacteria (including staphlycocci, streptococci, enterococci, listeria monocytogenes, clostridium sp, and Bacillus sp.), with limited gram negative activity.

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:
AMINOGLYCOSIDE

ANTIBIOTIC:
GLYCOPEPTIDE

ANTIBIOTIC:
QUINOLONE

aminoglycoside of choice because of its lower cost and reliable activity against GNB.
It is often used in combination
with a beta lactam antibiotic for serious but uncultured infections. They also have
limited gram positive coverage including staph and some strep

It possesses a broad spectrum of activity against gram positive bacteria including MRSA.
Acts synergistically with aminoglycosides, cephalosporins and rifampicin (although synergy testing required as vancomycin + cephalosporin may act antagonistically against some strains of staph epidermis)

Betalactam

Aminoglycoside

Tricyclic glycopeptide antibiotic produced by streptococcus orientalis

Quinolone

Level 1

Level 1

Level 1

Level 3

Level 1

clear solution for injection. Requires monitoring of levels especially
if there is any renal impairment, to prevent complications

Store at 2-8 degrees, clear solution. Slowly due to vessel irritation (& risk of red man syndrome).
Monitoring required to avoid toxic levels (aiming serum conc 15+/-3).

PO and IV, topical eye drops and ointment

Bacteria produce beta lactamases, which hydrolyse and inactivate the antibiotic

Resistance
MRSA
Many Staph
-Betalactamase prod

Alteration in access to target site – membrane impermeability / transport defect in the active transport.
Lack of O2-transport channels: Anaerobes
Multiple enzymes which block gentamicin (acetytransferases, adenyltransferases, phosphotransferases)

VanA resistance – gene mutation leading to decreased affinity of peptidoglycan precursors for vancomycin.
Induced by exposure to vanc / teicoplanin
Van B resistance – similar but only induced by vancomycin; strains may remain susceptible to teicoplanin

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