A Gram‑negative bacillus isolated from a urinary tract infection shows resistance to third‑generation cephalosporins due to production of extended‑spectrum β‑lactamase (ESBL). (a) Explain the biochemical mechanism by which ESBL confers resistance to these antibiotics. (b) Propose an oral antibiotic that would be effective against this organism and justify your choice based on its mechanism and the resistance profile.
Answer
(a) ESBL enzymes hydrolyse the β‑lactam ring of third‑generation cephalosporins, rendering the drug inactive. (b) A fluoroquinolone such as ciprofloxacin is effective because it is orally available, penetrates urine, and is not hydrolysed by ESBL enzymes. Alternatively, a carbapenem like ertapenem could be used, but it is not available orally.
Step-by-step solution
- Describe ESBL as a β‑lactamase capable of hydrolysing the β‑lactam ring.
- Explain that hydrolysis destroys the antibacterial activity of third‑generation cephalosporins.
- Identify that ESBL does not inactivate fluoroquinolones.
- State that ciprofloxacin is orally available and penetrates the urinary tract, making it suitable.
- Mention that carbapenems are also not hydrolysed by ESBL, but lack oral formulations, so ciprofloxacin is the practical choice.
Common mistake: Assuming ESBL also inactivates carbapenems
Concept tested: Mechanism of ESBL resistance and treatment choice
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