Aminoglycosides: mechanism and resistance MCQs With Answer

Aminoglycosides: mechanism and resistance MCQs With Answer

Introduction: This quiz set is designed for M.Pharm students preparing for Advanced Pharmacology-II. It focuses on aminoglycoside antibiotics, covering their molecular mechanism of action, pharmacodynamic properties, clinical uses, toxicities, and detailed mechanisms of bacterial resistance. Questions emphasize ribosomal interactions, oxygen-dependent uptake, enzymatic modification (AAC, ANT, APH), methyltransferase-mediated resistance, plasmid-encoded determinants, and clinical implications such as dosing strategies and therapeutic monitoring. Each item tests conceptual understanding and application relevant to postgraduate pharmacology exams and research. Use these MCQs to deepen your mechanistic knowledge and to prepare for both written and oral assessments.

Q1. Which primary molecular event explains the bactericidal action of aminoglycosides?

• Inhibition of peptidoglycan cross-linking by binding to PBPs
• Inhibition of DNA gyrase leading to double-strand breaks
• Irreversible binding to the 30S ribosomal subunit causing misreading of mRNA
• Disruption of bacterial cell membrane by detergent-like activity

Correct Answer: Irreversible binding to the 30S ribosomal subunit causing misreading of mRNA

Q2. Aminoglycoside uptake into Gram-negative bacteria requires which condition for effective transport across the cytoplasmic membrane?

• Low extracellular pH to protonate the drug
• Active electron transport chain and oxygen-dependent membrane potential
• Presence of β-lactamase enzymes
• High extracellular magnesium concentration

Correct Answer: Active electron transport chain and oxygen-dependent membrane potential

Q3. Which class of bacterial enzymes chemically modifies aminoglycosides and commonly mediates high-level resistance?

• β-lactamases
• Aminoglycoside-modifying enzymes: acetyltransferases (AAC), nucleotidyltransferases (ANT), phosphotransferases (APH)
• Methyltransferases that methylate 23S rRNA
• Peptidoglycan hydrolases

Correct Answer: Aminoglycoside-modifying enzymes: acetyltransferases (AAC), nucleotidyltransferases (ANT), phosphotransferases (APH)

Q4. Methylation of which ribosomal component is a well-known mechanism conferring high-level aminoglycoside resistance?

• Methylation of 16S rRNA
• Methylation of 23S rRNA
• Methylation of 30S ribosomal protein S12
• Methylation of peptidoglycan precursors

Correct Answer: Methylation of 16S rRNA

Q5. Which genetic element most commonly facilitates rapid horizontal spread of aminoglycoside resistance genes among Gram-negative bacteria?

• Chromosomal point mutations only
• Plasmids and transposons carrying AME and methyltransferase genes
• Spontaneous loss of ribosomal proteins
• Phage-mediated lysis

Correct Answer: Plasmids and transposons carrying AME and methyltransferase genes

Q6. The synergistic killing effect when aminoglycosides are combined with β-lactams is mainly due to:

• β-Lactams competing for the same ribosomal binding site
• β-Lactams increasing cell wall permeability facilitating aminoglycoside uptake
• β-Lactams inhibiting aminoglycoside-modifying enzymes
• β-Lactams neutralizing aminoglycoside toxicity

Correct Answer: β-Lactams increasing cell wall permeability facilitating aminoglycoside uptake

Q7. Which pharmacodynamic property best describes aminoglycoside killing activity?

• Time-dependent killing with need for continuous infusion
• Concentration-dependent killing with significant post-antibiotic effect
• Both time- and concentration-dependent equally
• Static activity only, requiring combination with bactericidal drugs

Correct Answer: Concentration-dependent killing with significant post-antibiotic effect

Q8. A point mutation in the rpsL gene encoding ribosomal protein S12 most directly causes resistance to which aminoglycoside?

• Gentamicin via enhanced uptake
• Streptomycin via reduced ribosomal binding
• Tobramycin via increased efflux pump expression
• Amikacin via enzymatic acetylation

Correct Answer: Streptomycin via reduced ribosomal binding

Q9. Which of the following clinical toxicities of aminoglycosides is primarily associated with accumulation in cochlear hair cells?

• Nephrotoxicity due to proximal tubular cell accumulation
• Ototoxicity leading to irreversible hearing loss
• Hepatotoxicity with elevated transaminases
• Bone marrow suppression with anemia

Correct Answer: Ototoxicity leading to irreversible hearing loss

Q10. Why are aminoglycosides generally ineffective against anaerobic bacteria?

• Anaerobes possess 50S ribosomes that do not bind aminoglycosides
• Aminoglycoside uptake requires oxygen-dependent membrane potential absent in anaerobes
• Anaerobes produce AAC enzymes constitutively
• Anaerobes sequester aminoglycosides in the cell wall

Correct Answer: Aminoglycoside uptake requires oxygen-dependent membrane potential absent in anaerobes

Q11. Which laboratory mechanism test specifically detects aminoglycoside-modifying enzymes in a bacterial isolate?

• Disk diffusion for β-lactams
• Matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) to detect modified drug peaks
• Catalase test
• Oxidase test

Correct Answer: Matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) to detect modified drug peaks

Q12. Which aminoglycoside is designed to resist many common aminoglycoside-modifying enzymes and is often used for multidrug-resistant infections?

• Streptomycin
• Amikacin
• Neomycin
• Gentamicin

Correct Answer: Amikacin

Q13. Acquisition of 16S rRNA methyltransferase genes (e.g., armA) results in what phenotype?

• Sensitivity to all aminoglycosides due to enhanced uptake
• High-level, broad-spectrum aminoglycoside resistance by blocking drug binding
• Resistance only to streptogramins
• Loss of plasmid-mediated β-lactam resistance

Correct Answer: High-level, broad-spectrum aminoglycoside resistance by blocking drug binding

Q14. What is the primary clinical rationale for once-daily (extended-interval) aminoglycoside dosing?

• To reduce the incidence of hepatotoxicity
• To exploit concentration-dependent killing and allow renal recovery to reduce nephrotoxicity
• To maintain constant plasma levels for time-dependent killing
• To avoid interaction with β-lactam antibiotics

Correct Answer: To exploit concentration-dependent killing and allow renal recovery to reduce nephrotoxicity

Q15. Which resistance mechanism reduces intracellular aminoglycoside concentration by actively transporting the drug out of the cell?

• Ribosomal methylation
• Aminoglycoside-modifying enzymes
• Efflux pump overexpression
• Loss of porin channels only

Correct Answer: Efflux pump overexpression

Q16. A bacterial isolate exhibits decreased aminoglycoside susceptibility due to decreased permeability. Which structural change most likely causes this?

• Overproduction of 16S rRNA methyltransferase
• Loss or modification of outer membrane porin proteins
• Mutation in DNA gyrase
• Upregulation of peptidoglycan synthesis

Correct Answer: Loss or modification of outer membrane porin proteins

Q17. Which laboratory parameter is most important to monitor to minimize aminoglycoside toxicity during therapy?

• Daily liver function tests
• Serum trough concentrations and renal function (serum creatinine)
• Complete blood count for neutropenia
• Serum potassium monthly

Correct Answer: Serum trough concentrations and renal function (serum creatinine)

Q18. Enzymatic acetylation of aminoglycosides is catalyzed by which enzyme family and what is their substrate specificity principle?

• β-lactamases that hydrolyze the drug’s β-lactam ring
• AAC enzymes (acetyltransferases) that transfer acetyl groups to amino moieties of aminoglycosides, varying by enzyme and drug
• NADH-dependent oxidases that oxidize the sugar moiety
• Ribosomal methyltransferases that methylate protein components

Correct Answer: AAC enzymes (acetyltransferases) that transfer acetyl groups to amino moieties of aminoglycosides, varying by enzyme and drug

Q19. How does combined use of an aminoglycoside with a β-lactam antibiotic reduce the development of resistance clinically?

• β-Lactams inhibit aminoglycoside-modifying enzymes directly
• β-Lactams increase uptake of aminoglycosides and reduce selective pressure on a single target, lowering emergence of resistant mutants
• β-Lactams prevent renal accumulation of aminoglycosides
• Combination prevents ototoxicity and nephrotoxicity

Correct Answer: β-Lactams increase uptake of aminoglycosides and reduce selective pressure on a single target, lowering emergence of resistant mutants

Q20. Which molecular diagnostic finding in a clinical isolate would most strongly predict pan-aminoglycoside resistance?

• Presence of a single aac(3) gene only
• Detection of 16S rRNA methyltransferase gene such as armA or rmtA
• Mutation in porin gene alone
• Elevated catalase activity

Correct Answer: Detection of 16S rRNA methyltransferase gene such as armA or rmtA

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