USMLE1-AntiBacterial-Pencillins-1

PENICILLINS-1

The structure common to all penicillins is a beta-lactam ring fused with a thiazolidine nucleus.

Mechanism of Action:

• Bactericidal, require intact beta-lactam ring structure for activity.
• Bind to Penicillin-binding proteins(PBPs) on cytoplasmic membrane, then decrease transpeptidation reactions involved in “cross-linking” of peptidoglycan chains
• Activation of autolytic enzymes.

Mechanisms of Resistance:

• Penicillinases(beta-lactamases) break Lactam ring structure (eg;Staphylococci).
• Structural change in PBPs (eg;Methicillin Resistant Staphylococcus aureus [MRSA], penicillin resistant pnemococci)
• Change in Porin structure (eg;Pseudomonas)
• Reduced permeability - gram –ve organism.

Penicillins may be classified into four groups:

1. Natural penicillins (G and V)
2. Antistaphylococcal (penicillinase resistant) penicillins
3. Aminopenicillins
4. Antipseudomonal penicillins.

Note: Natural penicillins have therapeutic effects limited to streptococci and a few gram-negative organisms.

Natural penicillins:

• Penicillin G
• Penicillin V

Antistaphylococcal penicillins (penicillinase resistant Pc):

• Nafcillin , Oxacillin,Cloxacillin, Flucloxacillin, Dicloxacillin

Aminopenicillins:

• Ampicillin ,Amoxicillin

Antipseudomonal penicillins:

• Carbenicillin, Mezlocillin, Piperacillin, Ticarcillin.

Clinical uses of penicillin G:

• Endocarditis caused by S. viridans (or Streptococcus bovis)
• Pharyngitis (group A –beta hemolytic streptococci)
• Cat bite cellulitis (Pasteurella multocida)
• Syphilis (Treponema pallidum)--->Pc G DOC
• Intravenous penicillin G---->DOC for meningitis caused by S. pneumoniae.
• Benzathine penicillin G(IM route)---> DOC for rheumatic fever prophylaxis

Clinical uses of penicillin V:

• Penicillin V is used to treat streptococcal infections when oral therapy is appropriate and desirable.
• Penicillin V (oral route) DOC--->for rheumatic heart disease/carditis prophylaxis may be casued by ARF/RF

Antistaphylococcal (penicillinase resistant) Pc:

• Nafcillin, oxacillin, cloxacillin, and dicloxacillin are more resistant to bacterial beta-lactamases than is penicillin G.
• Nafcillin : Primariliy eliminated through the biliary route.

Indications of Antistaphylococcal (penicillinase resistant) Pc:
severe staphylococcal infections like:

• Cellulitis (but….Group A streptococci is the causative agent for rapidly spreading cellulitis and necrotizing fasciitis in most healthy young patients).
• Erysipelas: a specific form of cellulitis
• Empyema (collection of pus within a naturally existing anatomical cavity, such as the lung pleura)
• Endocarditis, Osteomyelitis, Pneumonia, Septic arthritis, Toxic shock syndrome.

Aminopenicillins: Ampicillin, Amoxicillin
good oral bioavailability

• ampicillin is effective treatment for meningitis caused by Listeria monocytogenes.

Indications for ampicillin include:

• meningitis caused by Listeria monocytogenes--->DOC
• serious infections like enterococcal endocarditis
• pneumonia caused by beta-lactamase-negative H. influenzae.

Amoxicillin oral therapy is appropriate for

Clinically acute nonserious bacterial infections like otitis media and sinusitis.

Amoxicillin also has use in multidrug regimens for the eradication of Helicobacter pylori in duodenal and gastric ulcers.

Aminopenicillins uses:

Infections caused by the following organisms:

• Haemophilius influenzae
• E.coli
• Listeria monocytogenes
• Proteous mirabilis
• Salmonella typhi

Ampicillin

• Active against gram +ve and gram - ve organisams
• Diarrhea is a side effect

Aminopenicillins

• Active against gram +ve (mainly) and gram -ve organisams.

Antipseudomonal Penicillins:  Carbenicillin, Ticarcillin, Mezlocillin, Piperacillin

The antipseudomonal penicillins have comparable spectra of activity against many gram-positive and gram-negative pathogens, including most anaerobes.

Antipseudomonal penicillins are used to treat

• Pneumonias associated with cystic fibrosis--->DOC (Fluroquinolone e.g. Ciprofloxacin also DOC)
• Mechanical ventilation---For prophylaxis of pseudomonal infection--->DOC
• UTI (if…..caused by E.coli, Pseudomonas, proteus, Kebsiella)
• It has good activity against Pseudomonas aeruginosa
• ►High dose cause bleeding by interfering with platelet function.