• Note that a predictable adverse reaction of an antibiotic such as nausea and vomiting is different from a true allergy – in this case antibiotic can be used with monitoring and management of the side effect
• Immediate hypersensitivity response – urticaria, bronchospasm, angioedema, anaphylaxis – potentially life-threatening
  • Avoid and find an appropriate non-b-lactam antibiotic
  • On the advice of an immunologist or infectious diseases specialist, desensitization may be considered
• Delayed hypersensitivity – rash (maculopapular) onset days after commencing
  • May be appropriate to use anotherb-lactam antibiotic in this context or even penicillin if the history suggests other factors involved. Should be commenced with close review
  • 5% cross-reactivity with cephalosporins (less than previously thought)
  • 1% cross-reactivity with carbapenems

• Gram positives: Streptococcus, Staphylococcus, faecalis
• Anaerobes (some penicillins)
• Gram negatives: coli, Klebsiella, Pseudomonas, Neisseria (gonorrhoea, meningitidis), Haemophilus

• Since their early use resistance to penicillins has been a problem
• Resistance is mainly due to production of enzymes (b-lactamases) that destroy b-lactam ring of penicillins
• Production of b-lactamases may be chromosomal or plasmid-mediated (plasmids can be transferred between bacteria)

• Factors to Consider
  • Patient Factors
    • age
    • weight
    • renal function (most penicillins are renally excreted)
  • Organism Factors
    • site of infection (if CNS infection then likely require higher dose)
    • MIC – minimum concentration to inhibit growth (important in endocarditis)
• Penicillinsare excreted rapidly hence the dosing intervals are often relatively short (4-6 hourly)
• Dose and interval reduction often required for renal impairment
  • Electronic Therapeutic Guidelines (eTG) is a good guide
• Somepenicillins can cause hepatic toxicity (e.g. flucloxacillin)
  • Usually dose and interval adjustment is not required in liver disease
  • Liver function should be monitored in patients in whom it is a concern
• For the above case start with 1g flucloxacillinQID
  • If admission is required, start with IV and when clinically improving convert to oral

• Drug interactions with penicillins are not as common as with some other drugs
• Probenecid (used for treatment of gout) is renally excreted and consequently impairs penicillin excretion
  • This is exploited to optimise penicillin dosing in certain settings (eg outpatient, hospital in the home)
• Oral contraceptive pill for some but not all penicillins

• Common and class-wide
  • gastrointestinal (vomiting, diarrhoea)
  • rash
  • drug fever
• Tazocin-specific
  • platelet dysfunction
  • neutropaenia
  • deranged LFTs
• Rare side effects
  • haemolyticanaemia
  • interstitial nephritis
  • seizures

• Patients heavily pretreated with broad spectrum antibiotics
• If fevers persist and inflammatory markers remain elevated despite appropriate antibiotic cover
• History of overseas travel to areas with prevalent multi-drug-resistant organisms (eg India)

Resources Available to Aid Antibiotic Prescription

• eTG – classes, spectra, dose adjustment
• Antimicrobial Stewardship program at individual hospitals
• Local policies and guidelines
• Local infectious disease team or microbiologist

• Penicillins were the first class of antibiotics discovered and still have a role to play despite the emergence of resistance
• Adhering to local guidelines will ensure selection of the right drug for the right patient at the right dose for the correct indication and help preserve penicillins for ongoing use
• Always consider both host and organism factors when prescribing antibiotics

• Calderwood, S B. PencillinsUpToDate May 2015