Antibiotics

Inhibitors of Cell Wall Synthesis

PENICILLINS
Structure

All based on the penicillin nucleus (beta-lactam ring)
Chemical synthesis or chemical modification of compounds produced by bulk fermentation of Penicillium moulds

Mechanism

Inhibit formation of peptidoglycan component of the bacterial cell wall
Dividing cells swell osmotically and rupture i.e. bacteriocidal against dividing cells
Resistance conferred by bacterial production of a beta-lactamase which hydrolyses the beta-lactam ring

Adverse effects

Generally well tolerated
Occasional diarrhoea
Allergic reactions including anaphylaxis occur (10% cross reactivity with cephalosporins)

Note

benzylpenicillin cannot be given orally due to hydrolysis by gastric acid
penicillins generally excreted by the kidney (by probenecid-sensitive organic acid transporter)
IV terminal half-life generally short (<2hrs)*

* hence
high peak level (cidal levels) then rapid clearance to low level of
antibiotic to minimise emergence of resistance. e.g. benzylpenicillin
(pen G) IV and phenoxymethylpenicillin (pen V) PO.
Narrow spectrum i.e. gram-positive cocci, gram-positive bacilli & gram-negative cocci
Note

Fully sensitive to penicillinases (all staph should be assumed to be resistant)
Also useful for some spirochaetal infections e.g. leptospirosis and syphilis
Benzylpenicillin is more active than phenoxymethylpen (i.e. not ***************alent potency)

Antistaphylococcal penicillins (-CLOXACILLINS)
e.g. flucloxacillin (Methicillin belongs to this class but it is no longer used clinically; laboratory resistance denotes MRSA status)
Mechanism

Possession of acyl side-chain prevents hydrolysis (of beta-lactam bond)

Adverse effects

cholestatic jaundice
allergic reactions

Notes

Generally
less active (10-20 times versus benzylpen) against penicillin-sensitive
non-staph organisms, thus if mixed infection should use in combination
with benzylpenicillin.

Broad spectrum penicillins e.g. Ampicillin* and amoxycillin.
* pivampicillin is a precursor that is converted in the gut
Mechanisms
chemical modification confers:

Activity against gram negative bacilli e.g. haemophilus influenzae and coliforms
Increased activity against enterococcus (strep.) faecalis
Still degraded by penicillinases

Adverse effects

Ampicillin commonly causes diarrhoea
Ampicillin rash frequent (if not diagnostic) in glandular fever
Allergic reactions

Note

Augmentin is a combination of amoxycillin plus clavulanic acid (penicillinase inhibitor)

<blockquote> - active against penicillinase producing staphylococci, E. coli and H. influenzae</blockquote>
<blockquote> - clavulanic acid is itself associated with diarrhoea and jaundice</blockquote>

Mecillinam is closely related to the broad-spectrum penicillins but has a very different spectrum of activity

<blockquote>- active against gram negatives inc penicillinase producing enterobacteriae
</blockquote><blockquote>- no activity against gram positives or pseudomonas</blockquote><blockquote>- specialist use only</blockquote>

Anti-pseudomonal penicillins
e.g. piperacillin, azlocillin, ticarcillin, carbenicillin

Notes

Expensive agents for specialised use only
Against non-pseudomonads similar spectrum to ampicillin but less effective
Useful for gram-negative infections especially with pseudomonas
Rashes are common

Timentin is ticarcillin plus clavulanic acid
Tazocin is piperacillin plus clavulanic acid

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