Protein Synthesis Inhibitors

Study Questions
Choose the ONE best answer.
30.1 Which of the following adverse effects is often employed as a therapeutic use for erythromycin?
A. QTc prolongation
B. Increased gastrointestinal motility
C. Photosensitivity
D. Deposition in bone

Correct answer = B. Macrolides, but especially erythromycin, cause GI distress and increase motility of the GI
tract, which is often used to treat gastroparesis and/or postoperative ileus. QTc prolongation is an adverse effect
of erythromycin but not one employed therapeutically. Photosensitivity and deposition in bone are adverse effects
of tetracyclines.

30.2 Which of the following describes the mechanism of action of tetracycline antibiotics?
A. Bind the 30S subunit of the bacterial ribosome, preventing binding of tRNA to the mRNA–ribosome complex.
B. Bind the 30S ribosomal subunit, interfering with assembly of the functional ribosomal apparatus.
C. Bind irreversibly to a site on the 50S subunit of the bacterial ribosome, inhibiting translocation steps of protein
synthesis.
D. Bind the bacterial 23S ribosomal RNA of the 50S subunit, inhibiting the formation of the 70S initiation complex.

Correct answer = A. Tetracyclines enter susceptible organisms via passive diffusion and also by an energy-
dependent transport protein mechanism unique to the bacterial inner cytoplasmic membrane. The drugs bind
reversibly to the 30S subunit of the bacterial ribosome. This action prevents binding of tRNA to the mRNA–
ribosome complex, thereby inhibiting bacterial protein synthesis. B is the mechanism for aminoglycosides, C is
the mechanism for macrolides, and D is the mechanism for oxazolidinones.

30.3 Linezolid would be a good choice for antibiotic treatment in which of the following patient scenarios?
A. Bacteremia caused by Staphylococcus aureus
B. Urinary tract infection caused by Escherichia coli
C. Pneumonia caused by drug-resistant Streptococcus pneumoniae
D. Diabetic foot infection caused by Pseudomonas aeruginosa

Correct answer = C. Linezolid does have coverage against resistant S. pneumoniae. It is not an optimal choice for
treatment of bacteremia. Linezolid also does not have gram-negative coverage against E. coli and P. aeruginosa.

30.4 After 5 days of clindamycin treatment for a skin infection, a patient develops diarrhea (10 watery stools/day),
severe abdominal pain, and fever. Which of the following organisms would you be concerned about as the
causative pathogen of diarrhea?
A. Escherichia coli
B. Bacteroides fragilis
C. Staphylococcus aureus
D. Clostridium difficile

Correct answer = D. Clindamycin use has been associated with Clostridium difficile–associated diarrhea. This
infection should be considered in a patient who presents with diarrhea while on clindamycin.

30.5 Which of the following statements accurately describes the difference in spectrum of activity between
erythromycin and azithromycin?
A. Azithromycin has better activity against respiratory pathogens such as Haemophilus influenzae and Moraxella
catarrhalis but less potent activity against staphylococci and streptococci.
B. Erythromycin has the same activity as azithromycin against gram-positives and gram-negatives.
C. Azithromycin has better activity against staphylococci and streptococci compared to erythromycin.
D. Erythromycin has better activity against gram-negatives such as H. influenza.

Correct answer = A. Erythromycin has better activity against gram-positive organisms, so B and C are incorrect.
D is incorrect as azithromycin has better activity against H. influenza.

30.6 Which of the following antibiotic agents should not be given to children less than 8 years of age due to its
deposition in bone and teeth?
A. Azithromycin
B. Doxycycline
C. Linezolid
D. Quinupristin/dalfopristin

Correct answer = B. Tetracyclines are contraindicated in this age group because they are deposited in tissues
undergoing calcification, such as teeth and bone, and can stunt growth.

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 30.7 A 77-year-old woman was started on antibiotics for pneumonia treatment. After 3 days of antibiotic therapy,
the serum creatinine doubled. Which of the following antibiotics is most likely responsible for this increase
in serum creatinine?
A. Doxycycline
B. Clarithromycin
C. Tobramycin
D. Linezolid

Correct answer = C. Aminoglycosides such as tobramycin accumulate in the proximal tubular cells of the kidney
and disrupt calcium-mediated transport processes. This results in kidney damage ranging from mild, reversible
renal impairment to severe, potentially irreversible acute tubular necrosis. Nephrotoxicity is not commonly
associated with tetracyclines, macrolides or oxazolidinones.

30.8 A 24-year-old pregnant woman was diagnosed with community-acquired pneumonia and will be managed in
the outpatient setting. Which antibiotic is a safe option for this patient to treat her pneumonia?
A. Azithromycin
B. Doxycycline
C. Fidaxomicin
D. Gentamicin

Correct answer = A. Azithromycin is available orally and considered safe in pregnancy. Doxycycline should not
be used in pregnancy due to its ability to cross the placenta and affect bone and skeletal development in the fetus.
Fidaxomicin does not reach therapeutic concentrations in serum or at this site of infection. It concentrates in the
gut. Gentamicin crosses the placental barrier and may accumulate in fetal plasma and amniotic fluid. It would
also not be used clinically in this outpatient scenario.

30.9 Parents of a 1-month-old baby are told their child has developed “gray baby syndrome.” Which of the
following antibiotics did the baby likely receive?
A. Tobramycin
B. Linezolid
C. Erythromycin
D. Chloramphenicol

Correct answer = D. Gray baby syndrome is an adverse effect caused by chloramphenicol in neonates due to their
underdeveloped renal function and low capacity to glucuronidate the antibiotic. The other agents do not undergo
this glucuronidation.

30.10 Aminoglycosides are commonly used for their concentration-dependent bactericidal activity against which
group of organisms?
A. Gram-positive aerobes
B. Gram-negative aerobes
C. Gram-positive anaerobes
D. Gram-negative anaerobes

Correct answer = B. Although aminoglycosides (such as gentamicin) are sometimes used synergistically against
gram-positive aerobes, this is not their most common use. They are typically used for their activity against gram-
negative aerobes. Aminoglycosides do not have good anaerobic activity.

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Antimycobacterial Drugs
Study Questions
Choose the ONE best answer.
32.1 A 22-year-old female intravenous drug user was admitted to the hospital with a 4-week history of cough and
fever. A chest radiograph showed left upper lobe cavitary infiltrate. Cultures of sputum yielded M.
tuberculosis susceptible to all antimycobacterial drugs. The patient received self-administered isoniazid,
rifampin, pyrazinamide, and ethambutol. Two weeks following initiation of therapy, the patient is concerned
that her urine is a “funny-looking reddish color.” Which drug is the most likely cause?
A. Isoniazid
B. Rifampin
C. Pyrazinamide
D. Ethambutol

Correct answer = B. Rifampin (as well as rifabutin and rifapentine) and its metabolites may color urine, feces,
saliva, sputum, sweat, and tears a bright red-orange. Patients should be counseled that this is an adverse effect
which is not harmful, but can stain clothes and contact lenses.

32.2 A 32-year-old man has been on standard four-drug therapy for active pulmonary tuberculosis for the past 2
months. He has no other comorbid conditions. At his regular clinic visit, he complains of a “pins and
needles” sensation in his feet. Which drug is most likely causing this?
A. Isoniazid
B. Rifampin
C. Pyrazinamide
D. Ethambutol

Correct answer = A. Standard four-drug therapy for active pulmonary tuberculosis includes isoniazid. Isoniazid
can cause peripheral neuropathy with symptoms including paresthesias, such as “pins and needles” and
numbness.

32.3 A 32-year-old man who takes standard four-drug therapy for active pulmonary tuberculosis complains about
a “pins and needles” feeling in his feet. He is diagnosed with peripheral neuropathy. Which vitamin should
have been included in the regimen for this patient to reduce the risk of neuropathy?
A. Niacin
B. Pyridoxine
C. Thiamine
D. Ascorbic acid

Correct answer = B. Concurrent administration of pyridoxine (vitamin B6) prevents the neuropathic actions of
isoniazid. The relative deficiency of pyridoxine appears to be due to the interference of isoniazid with its
activation and enhancement of the excretion of pyridoxine.

32.4 A 23-year-old man was started on standard four-drug antimycobacterial therapy for treatment of active TB.
He has epilepsy, which is controlled with carbamazepine. He has had no seizures in 5 years; however, upon
return to clinic at 1 month, he reports having two seizures since his last visit. Which drug may be the reason
his carbamazepine is less effective?
A. Isoniazid
B. Rifampin
C. Pyrazinamide
D. Ethambutol

Correct answer = B. Rifampin is a potent inducer of cytochrome P450–dependent drug-metabolizing enzymes

32.5 A 26-year-old female HIV patient was recently diagnosed with active tuberculosis. Currently, she is on a
stable HIV regimen consisting of two protease inhibitors and two nucleoside reverse transcriptase inhibitors.
Which is the most appropriate regimen for treatment of her tuberculosis?
A. Rifampin + isoniazid + pyrazinamide + ethambutol
B. Rifabutin + isoniazid + pyrazinamide + ethambutol
C. Rifapentine + isoniazid + pyrazinamide + ethambutol
D. Rifampin + moxifloxacin + pyrazinamide + ethambutol

Correct answer = B. Rifabutin is recommended in place of rifampin in patients coinfected with HIV, since it is a
less potent inducer of CYP enzymes than rifampin. However, rifabutin is a CYP3A4 substrate and “bidirectional”
interactions may result. That is, other medications, such as the protease inhibitors, may affect the concentration of
rifabutin, requiring dose adjustment of rifabutin or use of alternative HIV agents.

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 32.6 A 28-year-old man with MDR-TB is receiving the following medications for treatment: pyrazinamide,
ethionamide, moxifloxacin, streptomycin, and para-aminosalicylic acid. Which drug in his regimen requires
monitoring for QT prolongation?
A. Pyrazinamide
B. Ethionamide
C. Moxifloxacin
D. Streptomycin

Correct answer = C. While rare, prolongation of the QT interval is associated with the fluoroquinolones. QT
interval prolongation is due to the blocking of voltage-gated potassium channels. Of the available quinolones,
moxifloxacin has the greatest risk. The risk may be minimized by avoiding coadministration of other medications,
which may prolong the QT interval. The other agents are not associated with QT prolongation.

32.7 A 46-year-old male patient with active tuberculosis is to be initiated on the four-drug regimen of isoniazid,
rifampin, pyrazinamide, and ethambutol. The patient reports no other conditions except gout. Which pair of
antituberculosis drugs has the potential to worsen his gout?
A. Rifampin and isoniazid
B. Ethambutol and pyrazinamide
C. Rifampin and ethambutol
D. Isoniazid and ethambutol

Correct answer = B. Ethambutol and especially pyrazinamide both may increase uric acid concentrations and
have the potential to precipitate gouty attacks. Pyrazinamide- and ethambutol-induced hyperuricemia may be
controlled by use of antigout medications, such as xanthine oxidase inhibitors. Symptoms of gout must be
monitored closely.

32.8 A 24-year-old man returns to the clinic 1 month after starting treatment for tuberculosis. He is receiving
isoniazid, rifampin, pyrazinamide, and ethambutol. He states that he feels fine, but now is having difficulty
reading and feels he may need to get glasses. Which drug may be causing his decline in vision?
A. Isoniazid
B. Rifampin
C. Pyrazinamide
D. Ethambutol

Correct answer = D. Optic neuritis, exhibited as a decrease in visual acuity or loss of color discrimination, is the
most important side effect associated with ethambutol. Visual disturbances generally are dose related and more
common in patients with reduced renal function. They are reversible (weeks to months) if ethambutol is
discontinued promptly.

32.9 A 36-year-old woman with multidrug-resistant tuberculosis is being treated with the following agents:
streptomycin, cycloserine, pyrazinamide, ethionamide, and p-aminosalicylic acid. Her physician recently
noticed that she appears confused and anxious, and has a slight tremor. Which drug is most likely
contributing to her current state?
A. Streptomycin
B. Cycloserine
C. Pyrazinamide
D. Ethionamide

Correct answer = B. Cycloserine easily penetrates the CNS and may cause adverse effects involving the nervous
system, including psychoses, drowsiness, tremor, paresthesia, aggression, and suicidal ideation, among others.
Patients should be monitored continually for these signs and symptoms.

32.10 Which is correct regarding clofazimine in the treatment of leprosy?

Correct answer = C. Clofazimine is a phenazine dye and causes bronzing (the skin pigment color will change
color, from pink to brownish-black), especially in fair-skinned patients. This occurs in a majority of patients, and
generally is not considered harmful but may take several months to years to fade after discontinuing the
medication.

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