20A05: Exam Report

Outline the mechanisms of antimicrobial resistance (50% of marks). Briefly outline the pharmacology of ciprofloxacin (50% of marks).

71% of candidates passed this question.

Most candidates had a structured answer to mechanisms of resistance that covered the major categories (alter target protein, prevent entry, efflux, degrade drug) and provided an example of a bacteria and the affected antibiotic, as was required to answer the question in full. Ciprofloxacin, whilst perhaps not a first line drug in the ICU, was not well known by many candidates. Better
answers included a brief outline of class, mechanism of action (action on DNA gyrase to inhibit replication), spectrum (Gram negatives particularly mentioning Pseudomonas, lesser Gram-positive cover, not anaerobes, some atypical), PK (with correct dose, wide penetration into tissues including bone/prostate etc., predominantly renal excretion), side effects/toxicity (common or
specific to cipro e.g. QT, tendinitis, arthropathy) and an example of resistance.

T1ii / 20A05: Outline the mechanisms of antimicrobial resistance (50 marks). Briefly outline the pharmacology of ciprofloxacin (50 marks)

Resistance = when the maximal level of the agent tolerated is insufficient to inhibit growth

  1. Natural – bacteria do not possess molecular target for that drug
  2. Acquired:

1. Modification of Antimicrobial Molecule

a. Chemical Alteration of the Antibiotic

        • Production of enzymes capable of introducing chemical changes to the antimicrobial molecule
        • Example: Aminoglycoside Modifying Enzymes (AMEs) which modify the hydroxyl/amino groups of the aminoglycoside, enabling resistance E Faecium

b. Destruction of the Antibiotic Molecule

        • b-lactamases produced by bacteria hydrolyse the b-lactam ring
        • \negates penicillin
        • still sensitive to cephalosporins
        • ESBLs = even more widespread resistance
        • R to cephalosporins/penicillin/b-lactamase inhibitors (Clav Acid)
        • Only Mero is effective

2. Prevention of Antibiotic Reaching Target

a. Decreased permeability

        • Many a/b have targets inside bacteria or on their membrane
        • Example: Vancomycin is not active against Gm- bacteria as it cannot penetrate the outer membrane
        • Example: P aeruginosa is very good at altering porin fn/expression to limit permeability of a/b

b. Efflux pumps

        • P aeruginosa possess an efflux system to pump a/b out of the cell

3. Change/Bypass of Target Site

      • Changing of target site = ¯affinity of drug
      • Example: VRE
        • Glycopeptides bind to D-Ala-D-Ala
        • Bacterial remodelling of cell wall to provide new substrate D-Ala-D-Lactate prevents Vancomycin binding
        • Especially common in enterococci (E Faecium)

4. Resistance Due to Global Cell Adaptive Processes

      • Example: Daptomycin resistance
      • Altered cell wall metabolism resulting in changes in surface charge of the bacteria and produces an electrostatic ‘repulsion’ of Daptomycin from the cell wall of enterococci





400mg (IV) q8h


500-750mg (po) bd (step-down)


Bacteristatic & Bactericidal


Inhibits DNA gyrase enzymes

Promotes breakage of DNA

Time v Concentration

Combination concentration and time dependent killing

Post dose effect



Doesn't Cover

Most G -ve including Pseudomonas

Atypicals including Legionella



Intra-abdominal (with Metronidazole)


Expansion of G -ve cover in setting of renal impairment/allergy where other drugs cannot be used (ie Aminoglycosides)



70% OBA.  Delayed by food


20% PPB


4 metabolites, probably hepatic


Renal excretion of metabolites


CNS – headache, insomnia, dizziness, hallucinations

Renal – interstitial nephritis

CVS – QTC prolongation, TdP, arrhythmias

GI – C Diff

Skin – toxic epidermal necrolysis

Drug Interaction – with warfarin, increases PT

MSK – long term use assosciated with msk toxicity particularly to cartilage ie AAA, spontaneous tendon rupture 


Can evolve on therapy