USMLE1-AntiBacterial - Pencillins-2

Beta-lactamase/Penicillinase inhibitors:
Clavulanic acid
Sulbactum
Tazobactum

• Beta-lactamases are enzymes produced by gram + ve & gram –ve organisms that inactivate beta lactam antibiotics by opening beta lactam ring.
• Beta lactamase inhibitors have--->no antibacterial activity of their own.

beta-lactam antibiotic + beta-lactamase inhibitors combinations
• Ampicillin-Sulbactam
• Ticarcillin-Clavulanic acid
• Piperacillin- Tazobactam
• Amoxicillin–Clavulanic acid

ü  Amoxicillin–clavulanic acid is the only combination drug with oral bioavailability.

Beta-lactamase inhibitor :
Clavulanic acid : Naturally occurring beta lactamase inhibitor Inhibits wide variety of beta lactamases
• Amoxicillin + Clavulanic acid
• Ticarcillin + Clavulanic acid
Sulbactum, Tazobactum: Semi synthetic beta-lactamase inhibitor Oral bioavailability poor

Combinations given parenterally
• Ampicillin + Sulbactum
• Piperacillin + Tazobactum
The addition of the beta- lactamase inhibitor significantly broadens the spectrum of antibacterial activity against beta-lactamase-producing organisms
Elimination of the combination drugs occur primarily by renal excretion. Therefore, all of the beta-lactamase inhibitor combinations require dose adjustments in patients with renal insufficiency

clinical uses: in treating infections with known or suspected mixed bacterial flora, such as biliary infections, diabetic foot ulcers, endomyometritis, and peritonitis

Penicillins safe in Pregnancy:
• Ampicillin
• Penicillin G
• penicillin V
Adverse Effects of Pencillins:
Penicillins are among the safest drugs , although adverse reactions do occur.
• Hypersensitivity:
The major antigenic determinent of Pc hypersensitivity is its metabolite. penicilloic acid which reacts with proteins and serve as a hapten to cause an immune reaction.Incidence 5% to 7% with wide range of reactions (types 1 to 4).
• Urticarial skin rash common, but severe reactions, including anaphylaxis are possible.
• Interstitial nephritis occurs with Methicillin.
• cross-allergenicity between individual Pc.
• GI distress(NVD),especially Ampicillin
• Diarrhea by disruption of normal balance of intestinal microorganisms
• Superinfections leading to Candidiasis or Colitis
• Neurotoxicity : Pcs are irritating to neural tissues and can provoke seizures
• Jarisch Herxheimer Reaction in the treatment of Syphilis, Penicillin injected in a secondary syphilitic patient produce fever, exacerbation of lesions and vascular collapse
• Maculopapular Rash common with Ampicillin. Although rashes can develop with all the Pc, maculopapular rashes are most common with ampicillin.