ß-lactam antibiotics: mechanisms and resistance MCQs With Answer

Introduction

This quiz collection on ß‑lactam antibiotics — mechanisms and resistance — is designed for M.Pharm students preparing for Advanced Pharmacology‑II. It summarizes core concepts: how ß‑lactams inhibit cell‑wall biosynthesis by targeting penicillin‑binding proteins, structural features that determine spectrum and stability, and the diverse molecular mechanisms bacteria evolved to resist them (altered PBPs, β‑lactamases, porin loss, efflux, mobile genetic elements). Questions emphasize clinical and laboratory relevance — β‑lactamase classes, inhibitor spectra, PK/PD principles, diagnostic tests and examples of resistance genes — to build understanding useful for therapeutics, antimicrobial stewardship and research.

Q1. Which statement best describes the primary molecular mechanism by which ß‑lactam antibiotics inhibit bacterial cell wall synthesis?

• Intercalation into the cell membrane causing depolarization
• Acylation of active‑site serine in penicillin‑binding proteins, inhibiting peptidoglycan transpeptidation
• Inhibition of DNA gyrase leading to impaired replication
• Blockade of 30S ribosomal subunit preventing protein synthesis

Correct Answer: Acylation of active‑site serine in penicillin‑binding proteins, inhibiting peptidoglycan transpeptidation

Q2. According to the Ambler molecular classification, which statement about ß‑lactamase enzyme classes is correct?

• Class B enzymes are serine hydrolases, while classes A, C and D are metallo‑enzymes
• Classes A, C and D are serine ß‑lactamases; class B are zinc‑dependent metallo‑ß‑lactamases
• Ambler classification groups enzymes by inhibitor susceptibility rather than sequence
• Class D enzymes require copper ions for activity

Correct Answer: Classes A, C and D are serine ß‑lactamases; class B are zinc‑dependent metallo‑ß‑lactamases

Q3. Methicillin resistance in Staphylococcus aureus (MRSA) is primarily mediated by which mechanism?

• Overproduction of chromosomal class C β‑lactamase
• Mutations in porin channels reducing drug uptake
• Acquisition of mecA gene encoding altered PBP2a with low affinity for ß‑lactams
• Efflux pump upregulation specific for penicillins

Correct Answer: Acquisition of mecA gene encoding altered PBP2a with low affinity for ß‑lactams

Q4. Which description correctly summarizes the spectrum of the newer non‑ß‑lactam inhibitor avibactam?

• Irreversible inhibitor active exclusively against class B metallo‑ß‑lactamases
• Non‑ß‑lactam inhibitor active against class A, many class C and some class D enzymes but not class B
• Broad inhibitor that inactivates all Ambler classes A–D equally
• Only effective against class C enzymes and inactive against class A carbapenemases

Correct Answer: Non‑ß‑lactam inhibitor active against class A, many class C and some class D enzymes but not class B

Q5. Which pharmacokinetic/pharmacodynamic (PK/PD) parameter most closely predicts clinical efficacy of ß‑lactam antibiotics?

• Peak concentration to MIC ratio (Cmax/MIC)
• Area under the concentration–time curve to MIC ratio (AUC/MIC)
• Time that free drug concentration remains above the MIC during dosing interval (T>MIC)
• Total daily dose irrespective of dosing interval

Correct Answer: Time that free drug concentration remains above the MIC during dosing interval (T>MIC)

Q6. A carbapenem‑resistant Enterobacterales isolate lacks detectable carbapenemase genes but shows high MICs to ertapenem and meropenem. The most likely resistance mechanism is:

• Overexpression of altered PBPs identical to mecA
• Combined loss or modification of outer membrane porins together with high‑level ESBL or AmpC production
• Acquisition of plasmid encoding aminoglycoside‑modifying enzymes
• Production of chloramphenicol acetyltransferase

Correct Answer: Combined loss or modification of outer membrane porins together with high‑level ESBL or AmpC production

Q7. The nitrocefin disk test used in microbiology laboratories detects ß‑lactamase production by which principle?

• Binding to PBPs causing color change
• Chromogenic hydrolysis of a cephalosporin substrate that changes color on ß‑lactam ring cleavage
• Measurement of pH decrease due to bacterial growth
• Electrochemical detection of liberated zinc ions

Correct Answer: Chromogenic hydrolysis of a cephalosporin substrate that changes color on ß‑lactam ring cleavage

Q8. Structurally, how do penicillins and cephalosporins differ in their fused ring systems?

• Penicillins have a dihydrothiazine ring fused to the ß‑lactam; cephalosporins have a thiazolidine ring
• Penicillins have a thiazolidine ring fused to the ß‑lactam; cephalosporins have a dihydrothiazine ring
• Both classes share an identical fused bicyclic core with no differences
• Penicillins contain an aromatic ring fused to the ß‑lactam while cephalosporins do not

Correct Answer: Penicillins have a thiazolidine ring fused to the ß‑lactam; cephalosporins have a dihydrothiazine ring

Q9. Extended‑spectrum β‑lactamases (ESBLs) are characterized by which of the following?

• Hydrolysis limited to penicillins and first‑generation cephalosporins only
• Hydrolysis of oxyimino‑cephalosporins (e.g., cefotaxime, ceftazidime) and inhibition by clavulanic acid
• Exclusive resistance to carbapenems and inhibition by EDTA
• Expression only in Gram‑positive cocci

Correct Answer: Hydrolysis of oxyimino‑cephalosporins (e.g., cefotaxime, ceftazidime) and inhibition by clavulanic acid

Q10. Which antibiotic is a potent inducer of chromosomal AmpC ß‑lactamase expression in organisms such as Enterobacter spp.?

• Cefepime
• Cefoxitin
• Aztreonam
• Linezolid

Correct Answer: Cefoxitin

Q11. Which structural modification distinguishes carbapenems from penicillins and contributes to their broad PBP affinity and relative stability to many ß‑lactamases?

• Replacement of the ß‑lactam carbonyl with an amide group
• Substitution of sulphur at position 1 of the fused ring by a carbon atom and an endocyclic double bond
• Attachment of a bulky aromatic R‑side chain identical to aminoglycosides
• Introduction of a quaternary ammonium group on the ß‑lactam ring

Correct Answer: Substitution of sulphur at position 1 of the fused ring by a carbon atom and an endocyclic double bond

Q12. Clavulanic acid enhances activity of amoxicillin primarily by which mechanism?

• Acting as a competitive PBP inhibitor that synergizes with amoxicillin
• Functioning as a membrane permeabilizer increasing drug uptake
• Being a mechanism‑based (suicide) inhibitor that irreversibly acylates many serine β‑lactamases
• Chelating divalent cations required for enzyme stability

Correct Answer: Being a mechanism‑based (suicide) inhibitor that irreversibly acylates many serine β‑lactamases

Q13. Penicillin‑binding proteins (PBPs) perform which essential enzymatic reaction during peptidoglycan synthesis?

• Polymerization of N‑acetylmuramic acid into long glycan strands
• Transpeptidation: cross‑linking peptide side chains by recognizing D‑Ala‑D‑Ala termini
• Removal of N‑acetylglucosamine residues from the glycan backbone
• Methylation of lipid II carrier molecules

Correct Answer: Transpeptidation: cross‑linking peptide side chains by recognizing D‑Ala‑D‑Ala termini

Q14. The “inoculum effect” relevant to ß‑lactam therapy refers to:

• Increased efficacy of antibiotics at higher bacterial densities
• Reduced susceptibility of bacteria to an antibiotic as the starting inoculum increases, often due to elevated ß‑lactamase production
• Faster bactericidal kinetics when inoculum is large
• Dependence of MIC determinations on the age of the antibiotic solution

Correct Answer: Reduced susceptibility of bacteria to an antibiotic as the starting inoculum increases, often due to elevated ß‑lactamase production

Q15. Clinical cross‑reactivity between penicillins and cephalosporins is most strongly associated with which factor?

• Shared intact ß‑lactam ring only, irrespective of side chains
• Similarity of the lateral (R) side‑chain structures rather than the common ß‑lactam nucleus
• Both classes always exhibit high cross‑reactivity so they should never be co‑administered
• Only generation of the cephalosporin determines cross‑reactivity, not side chains

Correct Answer: Similarity of the lateral (R) side‑chain structures rather than the common ß‑lactam nucleus

Q16. Which laboratory approach is commonly used to detect metallo‑ß‑lactamase (class B) activity by inhibition?

• Combined disk test using EDTA to chelate zinc and inhibit class B enzymes
• Nitrocefin test specifically differentiating class B from class A
• Modified Hodge test that uses clavulanic acid as inhibitor
• PCR for blaOXA‑48 only

Correct Answer: Combined disk test using EDTA to chelate zinc and inhibit class B enzymes

Q17. Which ß‑lactam/ß‑lactamase inhibitor combination is particularly effective clinically against KPC (class A carbapenemase) producing Enterobacterales?

• Piperacillin‑tazobactam
• Ceftolozane‑tazobactam
• Ceftazidime‑avibactam
• Amoxicillin‑clavulanate

Correct Answer: Ceftazidime‑avibactam

Q18. Aztreonam, a monobactam antibiotic, is unique among ß‑lactams because it:

• Has activity mainly against anaerobic Gram‑positive cocci
• Is inherently resistant to serine ß‑lactamases, including ESBLs
• Is active primarily against aerobic Gram‑negative bacilli and is stable to many metallo‑ß‑lactamases
• Exhibits potent activity against MRSA due to binding PBP2a

Correct Answer: Is active primarily against aerobic Gram‑negative bacilli and is stable to many metallo‑ß‑lactamases

Q19. The post‑antibiotic effect (PAE) of ß‑lactams is generally described as:

• Prolonged and significant against Gram‑negative organisms making once‑daily dosing optimal
• Minimal or short, particularly against Gram‑negative bacteria, so efficacy relies on maintaining T>MIC
• Irrelevant to dosing strategies because ß‑lactams are concentration‑dependent
• Dependent solely on protein binding and not on bacterial species

Correct Answer: Minimal or short, particularly against Gram‑negative bacteria, so efficacy relies on maintaining T>MIC

Q20. The global dissemination of CTX‑M type ESBLs (blaCTX‑M) has been most strongly linked to which genetic mobility mechanism?

• Chromosomal point mutations within the core genome without mobile elements
• Plasmid‑mediated transfer often mobilized by insertion sequence ISEcp1 and integron platforms
• Transduction exclusively by bacteriophages carrying mecA
• Spontaneous generation in response to antibiotic exposure without horizontal transfer

Correct Answer: Plasmid‑mediated transfer often mobilized by insertion sequence ISEcp1 and integron platforms

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