Beta-lactams

Beta-lactams inhibitors

1. Penicillins - PREPARATIONS OF PENICILLINS
   • BENZYL PENICILLIN - prophylaxis (Benzathine)/meningitis
   • Resistant Penicillin - one indication - Anti-Staph
   • Amino-Penicillins - Broad -SPECTRUM PENICILLINS
   • Anti-Pseudomonal Penicillins - -Ve pseudmonas & ampicillin resistant proteus
   • Amidino-Penicillens
2. Cephalosporins - 1st +Ve & 3rd -Ve except 2,4 broad - UTI’s, Bacterial Meningitis, RTI, ENT, Pseudomanl
3. Monobactams - -Ve activity
4. Carbapenems - antibiotic of last resort

All beta-lactams have a few things in common

1. All beta-lactams can cause hypersensitivity reactions, ranging from mild rashes to drug  fever to acute interstitial nephritis (AIN) to anaphylaxis. There is cross-reactivity between some agents (e.g., peniciilin and cephalosporin), but it is difficult to predict exactly how often that will occur.

   It seems that similarities between side chains of beta-lactams are responsible for cross-reactivity.

2. Seizures can result from very high doses of any beta-lactam, & some cause other neurologic effects. Accumulation to toxic levels can occur when the dose of a beta-lactam is not properly adjusted for a patient’s renal function Did you check your patient’s renal function? In that case change dosage strength

3. All beta-lactams share a mechanism of : Cidal

• They form complexes with (Irreversibly inhibit ) enzymes - trans- and carboxypeptidases (PCP), (i.e., penicillin binding proteins) in bacterial cell walls), which control synthesis of peptidoglycan – component of cell-wall of microorganisms (final steps of cell wall synthesis)=formation of peptide bridges between adjacent stands of peptidoglycan i.e  prevents cross linking of the glycan strands leading to leading to swelling and lysis, killing the organism.
  • Involves activation of autolytic enzymes in the cell wall, and results in lysis of organism.

4. All beta-lactams can be destroyed by beta-lactamases, enzymes produced by bacteria to destroy beta-lactams. Some beta-lactams such as penicillins are easily destroyed, whereas others such as carbapenems are stable against most beta-lactamases. But nature has shown us that whenever a beta-lactam is developed, a beta-lactamase capable of hydrolyzing it inevitably emerges.

   • B-Lactamase can be overcomed by :
   1. Give a B-Lactamase inhibitor at same time Clavulanic Acid & Sulbactam….etc EX: Augmentin
   2. Modify the antibiotic structure to make it more resistant EX: Amoxicillin

5. All beta-lactams lack activity against atypical organisms such as Mycoplasma pneumoniae and Chlamydia pneumoniae which lacks cell wall. so Add another drug to your regimen if you are concerned about these organisms, as in cases of community-acquired pneumonia (CAP).

6. All but one of the currently available beta-lactams lack activity against methicillin-resistant Staphylococcus (MRSA). So,  Add vancomycin or another agent if this bacterium is suspected.

The available beta-lactams, only the Cephalosporins ceftaroline has anti-MRSA activity 5th gen