Quinolones: mechanism and resistance MCQs With Answer

Introduction

The following quiz focuses on quinolones — a critical class of antibacterial agents studied in Advanced Pharmacology-II. It emphasizes their molecular mechanism of action, pharmacokinetic/pharmacodynamic relationships, and the major genetic and biochemical mechanisms that confer resistance. Questions are crafted for M.Pharm students and cover DNA gyrase and topoisomerase IV targeting, QRDR mutations, plasmid-mediated resistance (qnr, aac(6′)-Ib-cr, qepA, oqxAB), efflux and permeability changes, and laboratory/clinical implications of resistance. Use this set to test understanding of how quinolones kill bacteria, how resistance emerges and spreads, and how PK/PD principles guide dosing strategies to limit resistance development.

Q1. Which enzyme is the primary target of quinolones in Gram-negative bacteria?

• DNA gyrase (gyrA/gyrB)
• Topoisomerase IV (parC/parE)
• RNA polymerase
• Peptidoglycan transpeptidase

Correct Answer: DNA gyrase (gyrA/gyrB)

Q2. What is the principal bactericidal mechanism of quinolones?

• Inhibition of cell wall synthesis by preventing peptidoglycan cross-linking
• Stabilization of DNA–topoisomerase cleavage complexes leading to double-stranded DNA breaks
• Competitive inhibition of folate synthesis enzymes
• Disruption of the bacterial cell membrane via detergent-like action

Correct Answer: Stabilization of DNA–topoisomerase cleavage complexes leading to double-stranded DNA breaks

Q3. Which PK/PD index best correlates with quinolone efficacy and prevention of resistance?

• Time above MIC (T>MIC)
• Peak concentration to MIC ratio (Cmax/MIC)
• Area under the concentration–time curve to MIC ratio (AUC/MIC)
• Minimum bactericidal concentration (MBC)

Correct Answer: Area under the concentration–time curve to MIC ratio (AUC/MIC)

Q4. In many Gram-positive organisms (e.g., Streptococcus pneumoniae), the primary quinolone target at typical concentrations is:

• DNA gyrase
• Topoisomerase IV
• Ribosomal 30S subunit
• Cell wall autolysin

Correct Answer: Topoisomerase IV

Q5. Which of the following plasmid-mediated mechanisms protects DNA gyrase from quinolone binding?

• aac(6′)-Ib-cr acetyltransferase
• qnr-encoded pentapeptide repeat proteins
• oqxAB chromosomally encoded pump
• Mutated porin expression

Correct Answer: qnr-encoded pentapeptide repeat proteins

Q6. The aac(6′)-Ib-cr gene confers reduced susceptibility to certain fluoroquinolones by which mechanism?

• Pumping drug out of the cell via an efflux pump
• Acetylation of the quinolone molecule
• Altering the drug target through mutation
• Decreasing outer membrane porin expression

Correct Answer: Acetylation of the quinolone molecule

Q7. High-level quinolone resistance most commonly arises by which genetic process?

• Acquisition of single plasmid encoding a complete resistance pathway
• Stepwise accumulation of chromosomal point mutations in gyrA and then parC
• Loss of plasmids encoding susceptibility factors
• Overexpression of ribosomal protection proteins

Correct Answer: Stepwise accumulation of chromosomal point mutations in gyrA and then parC

Q8. Which plasmid-encoded gene is commonly associated with an efflux mechanism that reduces quinolone susceptibility?

• NorA
• QepA
• AcrAB
• gyrB

Correct Answer: QepA

Q9. A frequent mutation site in the quinolone resistance-determining region (QRDR) of gyrA in E. coli is substitution of which residue?

• Serine 83
• Glycine 45
• Lysine 65
• Alanine 120

Correct Answer: Serine 83

Q10. Induction of the bacterial SOS response during quinolone exposure contributes to resistance primarily by:

• Direct enzymatic degradation of the drug
• Increasing horizontal gene transfer and error-prone mutagenesis
• Enhancing outer membrane synthesis
• Stimulating peptidoglycan cross-linking

Correct Answer: Increasing horizontal gene transfer and error-prone mutagenesis

Q11. Which laboratory method is most definitive for identifying specific point mutations in gyrA or parC associated with quinolone resistance?

• Disk diffusion susceptibility testing
• DNA sequencing of the QRDR
• Culture on selective media
• Enzyme-linked immunosorbent assay (ELISA)

Correct Answer: DNA sequencing of the QRDR

Q12. The qnr proteins confer quinolone resistance by which of the following actions?

• Direct enzymatic degradation of fluoroquinolones
• Binding and protecting DNA–gyrase/topoisomerase complexes from quinolone inhibition
• Increasing drug efflux through the cell membrane
• Altering intracellular pH to inactivate the drug

Correct Answer: Binding and protecting DNA–gyrase/topoisomerase complexes from quinolone inhibition

Q13. Which statement best describes cross-resistance among fluoroquinolones?

• Resistance to one fluoroquinolone never affects others in the class
• Target site mutations often confer cross-resistance to multiple fluoroquinolones
• Plasma protein binding eliminates cross-resistance
• Cross-resistance only occurs with macrolides, not fluoroquinolones

Correct Answer: Target site mutations often confer cross-resistance to multiple fluoroquinolones

Q14. Coadministration of oral quinolones with divalent cation-containing antacids reduces oral absorption because:

• Divalent cations induce hepatic enzyme metabolism of quinolones
• Quinolones form insoluble chelate complexes with Mg2+/Ca2+, decreasing bioavailability
• Antacids increase intestinal motility and reduce contact time
• Antacids elevate gastric pH which chemically degrades quinolones

Correct Answer: Quinolones form insoluble chelate complexes with Mg2+/Ca2+, decreasing bioavailability

Q15. Which combination of resistance mechanisms most often results in the highest level of quinolone resistance?

• Single gyrA mutation combined with increased efflux or decreased permeability
• Single parC mutation alone
• Both gyrA and parC mutations together
• Only plasmid-mediated qnr without chromosomal mutations

Correct Answer: Both gyrA and parC mutations together

Q16. Which phenotypic test can suggest the presence of active efflux-mediated quinolone resistance?

• PCR amplification of parC
• Reduction in MIC when tested in the presence of an efflux pump inhibitor
• Observation of swarming motility on agar
• Latex agglutination assay for qnr proteins

Correct Answer: Reduction in MIC when tested in the presence of an efflux pump inhibitor

Q17. Which gene encodes an acetyltransferase that can modify and reduce susceptibility to ciprofloxacin?

• qnrA
• aac(6′)-Ib-cr
• gyrA
• parC

Correct Answer: aac(6′)-Ib-cr

Q18. Quinolones are classified pharmacodynamically as:

• Bacteriostatic agents
• Bactericidal agents
• Fungistatic agents
• Virucidal agents

Correct Answer: Bactericidal agents

Q19. The post-antibiotic effect (PAE) of quinolones refers to:

• The immediate bactericidal activity during drug exposure
• Persistent suppression of bacterial growth after drug concentrations fall below the MIC
• Enzymatic inactivation of the drug by bacteria
• Increased mutation rate during drug exposure

Correct Answer: Persistent suppression of bacterial growth after drug concentrations fall below the MIC

Q20. Which dosing strategy is most likely to minimize selection of quinolone-resistant mutants?

• Low daily doses for prolonged periods to reduce toxicity
• High-dose, short-duration regimens that achieve optimal AUC/MIC targets
• Intermittent subtherapeutic dosing to allow immune clearance
• Using quinolones only as topical agents

Correct Answer: High-dose, short-duration regimens that achieve optimal AUC/MIC targets

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