Macrolide antibiotics: mechanism and resistance MCQs With Answer

Macrolide antibiotics: mechanism and resistance MCQs With Answer is designed for M.Pharm students preparing for advanced pharmacology exams and clinical therapeutics. This collection emphasizes molecular mechanisms of macrolide action, intracellular pharmacokinetics, and the major genetic and biochemical routes by which bacteria evade macrolide therapy. Each question probes deeper concepts such as 23S rRNA binding sites, erm- and mef-mediated resistance, enzymatic inactivation, diagnostic D-testing, and structure-based strategies (e.g., ketolides) to overcome resistance. Answers are provided for rapid self-assessment. Use these MCQs to test conceptual understanding, reinforce mechanisms at the ribosomal and molecular level, and prepare for problem-solving in antimicrobial stewardship and resistance interpretation.

Q1. Which molecular target is primarily bound by macrolide antibiotics to exert their antibacterial effect?

• 30S ribosomal subunit decoding region
• DNA gyrase A subunit
• 23S rRNA of the 50S ribosomal subunit
• Cell wall transpeptidase (PBP)

Correct Answer: 23S rRNA of the 50S ribosomal subunit

Q2. What is the principal mechanism by which macrolides inhibit bacterial protein synthesis?

• Interruption of initiation complex formation at the 30S subunit
• Inhibition of translocation by blocking the peptide exit tunnel
• Direct inhibition of peptidyl transferase catalytic residue
• Cleavage of mRNA during elongation

Correct Answer: Inhibition of translocation by blocking the peptide exit tunnel

Q3. Methylation of which nucleotide in 23S rRNA is most commonly associated with high-level macrolide resistance mediated by erm genes?

• G748
• A2058 (Escherichia coli numbering)
• C2611
• U2506

Correct Answer: A2058 (Escherichia coli numbering)

Q4. The erm gene family confers resistance to macrolides by which mechanism?

• Active efflux of macrolides from the bacterial cell
• Mutation of ribosomal protein L4 to prevent binding
• Methylation of 23S rRNA causing cross-resistance to macrolide–lincosamide–streptogramin B (MLSB)
• Enzymatic hydrolysis of the macrolide lactone ring

Correct Answer: Methylation of 23S rRNA causing cross-resistance to macrolide–lincosamide–streptogramin B (MLSB)

Q5. The mef(A) gene typically mediates macrolide resistance by which mechanism?

• Ribosomal methylation producing high-level resistance
• Reduced outer membrane permeability
• Energy-dependent efflux pump specific for 14- and 15-membered macrolides
• Phosphotransferase-mediated drug inactivation

Correct Answer: Energy-dependent efflux pump specific for 14- and 15-membered macrolides

Q6. A Staphylococcus aureus isolate is erythromycin-resistant but clindamycin-susceptible. A positive D-test indicates which resistance mechanism?

• Constitutive mef-mediated efflux
• Inducible erm-mediated methylation of 23S rRNA
• Enzymatic hydrolysis by esterases
• Mutation in ribosomal protein L22 only

Correct Answer: Inducible erm-mediated methylation of 23S rRNA

Q7. Which enzymatic mechanism directly inactivates macrolides by phosphorylation?

• erythromycin esterase encoded by ereA
• macrolide phosphotransferase encoded by mph genes
• ribosomal methyltransferase encoded by erm genes
• acetyltransferase targeting 23S rRNA

Correct Answer: macrolide phosphotransferase encoded by mph genes

Q8. Ketolides (e.g., telithromycin) were developed to overcome macrolide resistance. Which feature best explains their improved activity against some erm-mediated strains?

• They exclusively target the 30S ribosomal subunit
• They bind additional contact points in 23S rRNA and have higher ribosomal affinity
• They are substrates for the mef efflux pump and get concentrated
• They inhibit bacterial DNA replication instead of protein synthesis

Correct Answer: They bind additional contact points in 23S rRNA and have higher ribosomal affinity

Q9. Which macrolide is associated with the least clinically significant CYP3A4 inhibition and fewer drug–drug interactions?

• Erythromycin
• Clarithromycin
• Azithromycin
• Telithromycin

Correct Answer: Azithromycin

Q10. Macrolide antibacterial activity is best described as which pharmacodynamic pattern?

• Concentration-dependent killing with short post-antibiotic effect
• Time-dependent (exposure-driven) killing with variable post-antibiotic effect
• Irreversible bactericidal action independent of concentration
• Synergistic only when combined with aminoglycosides

Correct Answer: Time-dependent (exposure-driven) killing with variable post-antibiotic effect

Q11. Mutations in which ribosomal proteins are commonly implicated in decreased macrolide binding leading to resistance?

• S12 and S5
• L4 and L22
• S10 and S14
• L1 and L2 only

Correct Answer: L4 and L22

Q12. A clinical isolate of Streptococcus pneumoniae carries mef(A) but not erm(B). Which pattern of macrolide susceptibility is most likely?

• High-level resistance to macrolides and clindamycin (MLSB phenotype)
• Low- to moderate-level resistance to 14- and 15-membered macrolides, clindamycin remains susceptible
• Pan-macrolide susceptibility due to lack of methylation
• Resistance only to azalides, susceptibility to 14-membered macrolides

Correct Answer: Low- to moderate-level resistance to 14- and 15-membered macrolides, clindamycin remains susceptible

Q13. Which statement is correct regarding macrolide binding relative to the peptidyl transferase center (PTC)?

• Macrolides bind directly to the catalytic site of the PTC blocking peptide bond formation
• Macrolides bind in the nascent peptide exit tunnel near the PTC and impede elongation/translocation
• Macrolides intercalate into mRNA and prevent codon recognition at the A site
• Macrolides bind to the 30S subunit and prevent tRNA alignment

Correct Answer: Macrolides bind in the nascent peptide exit tunnel near the PTC and impede elongation/translocation

Q14. Which clinical pathogen is a classic indication for macrolide therapy due to intrinsic lack of cell wall and susceptibility to protein synthesis inhibitors?

• Escherichia coli
• Mycoplasma pneumoniae
• Pseudomonas aeruginosa
• Enterococcus faecalis

Correct Answer: Mycoplasma pneumoniae

Q15. Which macrolide formulation/classically associated with cholestatic hepatitis (estolate form) should be used cautiously because of hepatic adverse effects?

• Azithromycin dihydrate
• Erythromycin estolate
• Clarithromycin extended-release
• Telithromycin oral suspension

Correct Answer: Erythromycin estolate

Q16. A key pharmacokinetic property that explains macrolides’ high tissue concentrations and clinical efficacy in intracellular infections is:

• Extensive binding to plasma albumin only
• Active uptake and accumulation in phagocytic cells (macrophages, neutrophils)
• Exclusive renal excretion with tubular reabsorption
• High blood–brain barrier penetration leading to CSF accumulation

Correct Answer: Active uptake and accumulation in phagocytic cells (macrophages, neutrophils)

Q17. Inducible expression of erm-mediated resistance is commonly regulated at the genetic level by which mechanism?

• Constitutive promoter upstream of erm always active
• Leader peptide/attenuator sequence that allows translation of erm upon macrolide-induced ribosomal stalling
• Horizontal transfer of plasmid-borne beta-lactamase genes
• Single nucleotide deletions in 23S rRNA causing frameshift

Correct Answer: Leader peptide/attenuator sequence that allows translation of erm upon macrolide-induced ribosomal stalling

Q18. Which laboratory method will most directly detect the genetic basis of macrolide resistance (erm or mef genes) in a bacterial isolate?

• Disk diffusion susceptibility testing only
• Polymerase chain reaction (PCR) targeting erm and mef genes
• Minimum inhibitory concentration (MIC) determination without genotyping
• Gram stain of the isolate

Correct Answer: Polymerase chain reaction (PCR) targeting erm and mef genes

Q19. Which macrolide is acid-labile and often formulated as prodrugs or salts to improve oral bioavailability?

• Azithromycin
• Clarithromycin
• Erythromycin
• Troleandomycin

Correct Answer: Erythromycin

Q20. In Streptococcus pneumoniae, which combination of resistance determinants is most likely to produce high-level macrolide resistance and clinical treatment failure with standard macrolides?

• Presence of mef(A) alone
• Presence of erm(B) alone or erm(B) combined with mef(A)
• Loss of outer membrane porins only
• Topoisomerase IV mutations

Correct Answer: Presence of erm(B) alone or erm(B) combined with mef(A)

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