Paper II — 2022 May (Supplementary) (2010 Scheme) — Q2
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Paper II
2022 May (Supplementary) (2010 Scheme)
Question
A 40 years old female patient admitted to hospital with a complaint of fever with chills
and right loin pain since 5 days. She is a known diabetic. Urine microscopy shows
plenty of pus cells and gram negative bacilli. Her serum creatinine is moderately
elevated. Ultra sonogram of abdomen suggestive of acute pyelonephritis of right
kidney.
(a) List four groups of drugs with example, useful against gram negative organisms 2 mark(s)
(b) Explain the mechanism of action and two adverse effects of each group 2 mark(s)
(c) Describe the mechanism of action of Fluoroquinolones 1 mark(s)
(d) Mention the antibiotics to be avoided for the above patient 1 mark(s)
Q26 marksEssays
Answer
a) Four groups of drugs active against Gram-negative organisms, with examples
Group
Example
Aminoglycosides
Gentamicin
Fluoroquinolones
Ciprofloxacin
Third-generation cephalosporins
Ceftriaxone
Carbapenems
Imipenem
b) Mechanism of action and two adverse effects of each group
Aminoglycosides — bind the 30S ribosomal subunit, causing misreading of the genetic code and blockade of the initiation complex, producing non-functional proteins (bactericidal despite being protein synthesis inhibitors). Adverse effects: nephrotoxicity (reversible acute tubular necrosis), ototoxicity (often irreversible, cochlear and vestibular).
Fluoroquinolones — inhibit DNA gyrase and topoisomerase IV, blocking DNA replication. Adverse effects: tendinopathy/tendon rupture, cartilage damage in developing joints (traditionally avoided in children/pregnancy).
Carbapenems — inhibit cell wall synthesis via penicillin-binding proteins, broadest beta-lactam spectrum. Adverse effects: seizures (imipenem, especially in renal impairment), hypersensitivity (partial cross-reactivity with penicillins).
c) Mechanism of action of fluoroquinolones
Fluoroquinolones inhibit two bacterial type II topoisomerase enzymes: DNA gyrase (introduces negative supercoils ahead of the replication fork, the primary target in Gram-negative organisms) and topoisomerase IV (separates interlinked daughter DNA circles after replication). Blocking these enzymes prevents DNA unwinding/religation, causing accumulated double-strand breaks and bactericidal cell death.
d) Antibiotics to avoid in this patient
Given her renal impairment (moderately elevated creatinine), aminoglycosides should be avoided or used only with extreme caution and dose adjustment — reduced clearance raises the risk of both nephrotoxicity and ototoxicity. Nitrofurantoin should also be avoided — it does not achieve adequate tissue levels for upper urinary tract infection (pyelonephritis) even in normal renal function, and is specifically contraindicated in renal impairment since inadequate urinary concentration reduces efficacy while systemic accumulation raises toxicity risk.
