A patient with community-acquired pneumonia is prescribed doxycycline.
Which statement best explains why doxycycline is effective against
Streptococcus pneumoniae despite the presence of a ribosomal protection
protein (TetM) in some strains?
A. Doxycycline has a higher affinity for the 30S subunit than TetM,
overcoming protection.
B. Doxycycline is actively transported out of the bacterial cell by efflux
pumps, reducing intracellular concentration.
C. Doxycycline inhibits the 50S subunit, bypassing TetM-mediated
resistance.
D. Doxycycline is not affected by TetM because TetM only protects
against aminoglycosides.
Correct Answer: A - Doxycycline has a higher affinity for the 30S
subunit than TetM, overcoming protection.
RATIONALE
TetM is a ribosomal protection protein that displaces tetracyclines
from the 30S subunit. Doxycycline, a second-generation tetracycline,
has higher affinity for the ribosome and can overcome TetM-mediated
resistance in some strains. Options B and C are incorrect because
doxycycline does not target the 50S subunit and efflux would reduce
efficacy, not enhance it. Option D is false; TetM specifically protects
against tetracyclines.
Question 2
Which pharmacokinetic property of aminoglycosides necessitates therapeutic
drug monitoring to minimize nephrotoxicity and ototoxicity?
A. Extensive hepatic metabolism to inactive metabolites.
B. Concentration-dependent killing with a narrow therapeutic index.
C. High oral bioavailability allowing outpatient administration.
D. Protein binding >90%, leading to drug accumulation in adipose tissue.
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,Correct Answer: B - Concentration-dependent killing with a
narrow therapeutic index.
RATIONALE
Aminoglycosides exhibit concentration-dependent killing, meaning
efficacy correlates with peak concentration (Cmax/MIC), while
toxicity correlates with sustained trough levels. Their narrow
therapeutic index requires monitoring of peak and trough levels.
Options A, C, and D are incorrect because aminoglycosides are not
hepatically metabolized, have negligible oral bioavailability, and have
low protein binding.
Question 3
A patient with myasthenia gravis develops a severe gram-negative infection
requiring aminoglycoside therapy. Which adverse effect is of greatest concern
due to the patient's underlying condition?
A. Nephrotoxicity
B. Ototoxicity
C. Neuromuscular blockade
D. Photosensitivity
Correct Answer: C - Neuromuscular blockade
RATIONALE
Aminoglycosides inhibit presynaptic calcium influx and reduce
acetylcholine release, potentially exacerbating muscle weakness in
myasthenia gravis. While nephrotoxicity and ototoxicity are common,
neuromuscular blockade is the most immediate and life-threatening
concern in this population. Photosensitivity is not associated with
aminoglycosides.
Question 4
Which statement accurately describes the mechanism of action of tetracyclines
at the 30S ribosomal subunit?
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, A. They cause misreading of mRNA codons, leading to premature
termination.
B. They block the binding of aminoacyl-tRNA to the A site, preventing
peptide elongation.
C. They inhibit peptidyl transferase activity, preventing peptide bond
formation.
D. They prevent the initiation complex from forming by binding to the
50S subunit.
Correct Answer: B - They block the binding of aminoacyl-tRNA
to the A site, preventing peptide elongation.
RATIONALE
Tetracyclines reversibly bind to the 30S subunit and block the
attachment of aminoacyl-tRNA to the A site, halting protein synthesis.
Aminoglycosides cause mRNA misreading (option A), while peptidyl
transferase inhibition (option C) is characteristic of chloramphenicol
and macrolides. Option D is incorrect because tetracyclines target the
30S, not 50S, subunit.
Question 5
A patient with a prosthetic joint infection due to methicillin-resistant
Staphylococcus aureus (MRSA) is being considered for doxycycline therapy.
Which factor most likely limits the use of doxycycline in this scenario?
A. Doxycycline is bactericidal against MRSA.
B. Doxycycline has poor penetration into bone and joint tissue.
C. Doxycycline is primarily excreted renally and requires dose
adjustment.
D. Doxycycline is inactive against MRSA due to efflux pumps.
Correct Answer: B - Doxycycline has poor penetration into bone
and joint tissue.
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