penicillins

see also:

• antibiotics

• penicillins belong to the group of antibiotics (including cephalosporins) which act upon the beta lactam ring and thus compromise the bacterial cell wall in a bactericidal manner
• penicillins act via binding to penicillin-binding proteins on the bacterial cell wall

• reactions to beta-lactam antibiotics can be classified into:
  • immediate
    • IgE mediated and classically manifest as anaphylaxis, urticaria, angioedema, bronchospasm and allergic rhinoconjunctivitis.
    • occurs in ~10% of patients with “allergy” to penicillin
    • while penicillin-induced anaphylaxis is rare (0.01-0.05% of courses), it may be fatal in 10% of cases
    • it is difficult to obtain reliable data about the frequency of cephalosporin anaphylaxis, but published figures are 0.0001-0.1%
  • non-immediate
    • such as maculopapular or morbilliform rashes are probably T-cell mediated.
    • less common but serious adverse reactions to cephalosporins include serum sickness-like reactions, acute interstitial nephritis and cytopenias.

• penicillins and cephalosporins exhibit partial and incomplete cross-reactivity
  • early studies in the 1960's and 1970's suggested that this was ~18% (ie 18% of patients with penicillin allergy would also have cephalosporin allergy), however, these studies were apparantly falsely high due in part to being done at a time when cephalospirins were often contaminated with penicillin
    • before the 1980s, pharmaceutical companies used Acremonium (formally called Cephalosporium) to create both penicillins and cephalosporins
    • in addition, the authors of the early studies loosely defined ‘‘allergy’’ and did not account for the fact that penicillin-allergic patients have an increased risk of adverse reactions to any medication
  • patients with a penicillin allergy have a ~3x normal risk of other allergies - even to medications not structurally related to penicillins
  • the overall cross reactivity between penicillins and cephalosporins in individuals who report a penicillin allergy is approximately 1% and, in those with a confirmed penicillin allergy, 2.55%. ¹⁾
  • cross-reactivity between penicillins and 3rd generation cephalosporins approaches 0% ²⁾
• Camapagna et al recommend that in patients with a documented IgE-mediated response to penicillin, third- and fourth-generation cephalosporins can be used generously. First- and second-generation cephalosporins with R1 side chains similar to that of penicillin (ie, cefaclor, cefadroxil, cefatrizine, cefprozil, cephalexin, and cephradine) should be avoided ³⁾
• a history of mild reactions to penicillin, such as rashes, does not imply that a reaction to cephalosporins will not be life-threatening - if a 1st or 2nd generation cephalosporin is prescribed to a patient with penicillin allergy, the first dose should be taken in a monitored setting ⁴⁾
• anaphylaxis

• mainly active against Gram +ves, Neisseria & enterococci
  • eg. benzyl penicillin, Pen V, procaine penicillin

• active against Staph. aureus but NOT MRSA
• eg. flucloxacillin, dicloxacillin, methicillin

• active against many Gram -ves but NOT Enterobacter, indole+ve Proteus
• eg. amoxycillin/amoxicillin, ampicillin

• active against Pseudomonas but used with aminoglycosides to prevent resistance developing.
• eg. carbenicillin, ticarcillin, piperacillin
• see also Tazocin (piperacillin + tazobactam)

• substances that resemble beta lactams & competitively inhibit beta lactamases
• used to extend the activity of penicillins
• eg. clavulanic acid, sulbactam, tazobactam (see Tazocin (piperacillin + tazobactam))