Beta-lactam Antibiotics

Composition

  • Contain a ‘beta-lactam’ ring structure
    • Note that a drawback of these antibiotics is that some bacteria can secrete beta-lactamases which breaks down this ring and thus inhibits the agent’s action

Mechanism of action/Pharmacokinetics

  • Bactericidal- inhibits enzymes involved in cell wall synthesis (preventing cross-linking of peptidoglycan in the cell wall)
  • Mostly metabolised/excreted via the kidneys (ceftriaxone has a biliary excretion component also)
  • Penicillins can distribute well to the urine, synovial fluid, pleural fluid, CSF.  They are useful for skin/soft tissue infections (Strep pyogenes), meningitis (N meningitidis or S pneumoniae)
  • Cephalosporins also have a fairly good distribution to the CSF and are used in a number of infections in the hospital setting.
  • Generally safe (see below for allergy)

Classification/examples

  • Penicillins
    • Natural penicillins e.g. benzylpenicillin and phenoxymethylpenicillin provides good cover against Gram-possitive organisms and anaerobic organisms: staphylococci, streptococci, neisseriae, spirochaetes and certain other organisms e.g. oral anaerobic organisms (e.g. in dental disease)
      • However, resistance (beta-lactamases) is largely found in staphylococci and gonnococci
      • Other staphylococci and pneumococci can be resistant to penicillin via other mechanisms
    • Aminopenicillins e.g. amoxicillin and ampicillin have the added ability to cover some Gram-negative organisms (enterobacteria)
      • Resistance is quite common so they are not routinely used first line for the treatment of gram-negative infections
        • Mostly due to beta-lactamase production.  This can be overcome by the addition of a beta-lactamase inhibitor e.g. clavulanic acid (e.g. co-amoxiclav) or sulbactam
    • Carboxypenicillins (e.g. ticarcillin) and ureidopenicillins (e.g. piperacillin) are very effective against Gram-negative organisms, particularly Pseudomonas spp. which is resistant to other types of antibiotics
      • Can also be enhanced by beta-lactamase inhibitors (e.g. tazocin: piperacillin + tazobactam)
  • Cephalosporins
    • Structure
      • Beta-lactam ring is fuse with a dihydrothiazide ring (cf thiazolidine ring of penicillins)
    • Efficacy/Clasification
      • Generally good broad-spectrum agents.
      • No effect against Enterococcus spp
      • First-generation cephalosporins (e.g. cephalexin)
        • Rarely used in hospital setting, (occasionally in the community)
        • Effective against Gram-Positive aerobic cocci e.g. Strep pyogenes (group A strep), Group B strep and streptococcus viridans
      • 2nd generation (e.g. cefuroxime)
        • less active against gram-positive but more active against gram-negative organims.  Cephamycins are also active against anaerobic Gram-negative bacilli
      • 3rd generation (e.g. cefotaxime, ceftriaxone)
        • generally broad-spectrum, covering a spread of both gram-positive (e.g. S aureus, Group A and B strep, Strep pneumoniae) and gram-negative organisms (e.g. H influenzae, Moraxella, Neisseria and Enterobacteriaceae)
        • generally used in hospital-acquired/severe gram-negative organism infection e.g. bacterial meningitis
  • Others 
    • Carbapenems e.g. Imipenem
      • Often an antibiotic of last resort and is truly broad-spectrum

NOTE: Beta-lactam antibiotics tend to work synergistically with aminoglycoside

Adverse effects

  • Penicillin allergy affects 0.7-10% of patients
    • Note it is important to ask about the features of the ‘allergy’ (distinguish from an intolerance)
    • DO NOT prescribe penicillins to a penicillin allergic patient. Avoid cephalosporins also where possible
  • Cephalosporins are associated with C difficile infection and so they are rarely used without a laboratory (and C&S) diagnosis
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