1.
A 65-year-old woman was admitted to the emergency room with altered consciousness,
fever (103.6° F), nausea and vomiting.. Vital signs on admission were: blood pressure 90/50
mm Hg , pulse 115 bpm, respirations 20/min. Physical examination showed a patient in
obvious distress with stiff neck and positive Brudzinski's sign. Pupils were equal, poorly
reactive to light and papilledema was present. An empirical IV therapy was started with
ampicillin, ceftriaxone and vancomycin. Which of the following phrases best explains the
mechanism of action common to all the given drugs?
Correct Answer
E. Inhibition of peptidoglycan synthesis
Explanation
Learning objective: Explain the mechanism of action common to ampicillin, ceftriaxone and
vancomycin.
Answer: E
The signs and symptoms of the patient strongly suggest the diagnosis of meningitis. When the
patient is very ill and the offending organism is unknown an empiric triple antibiotic therapy is
usually given, pending CSF test results. Third generation cephalosporins like ceftriaxone are active
against most gram positive and gram negative bacteria. Since many MR resistant cocci are
increasingly prevalent, vancomycin is usually added. Ampicillin is added to cover Listeria species.
All these antibiotic act by inhibiting the synthesis of peptidoglycan. Ampicillin and ceftriaxone inhibit
the transpeptidation reaction so blocking the cross link formation. Vancomycin inhibits
transglycosylase, so blocking further elongation of peptidoglycan chain.
2.
The diagram below depicts a simplified pathway for the synthesis and breakdown of
bacterial cell wall.
Which of the steps shown in the pathway is specifically inhibited by beta-lactam antibiotics?
Correct Answer
C. 3
Explanation
Learning objective: identify the specific step of the synthesis and breakdown of bacterial cell
wall which is inhibited by beta-lactam antibiotics.
Answer: C
Beta-lactam antibiotics inhibit cell wall synthesis by preventing cross-linking between the peptide
chains of the acetylmuramic acid. This linking is catalyzed by transpeptidase enzymes and beta
lactam antibiotics specifically inhibit these enzymes.
A) This step is inhibited by fosfomycin
B) This step is inhibited by vancomycin
D) This step is enhanced (not inhibited) by beta-lactam antibiotics and this action, together with the
inhibition of transpeptidase, contributes to the final bactericidal effect of these drugs.
3.
A 67-year-old man recently diagnosed with Legionnaires’ disease, started a treatment with
a macrolide antibiotic. Which of the following is the primary site of action of the drug on
bacterial cells?
Correct Answer
G. The ribosomes
Explanation
Learning objective: identify the site of action of clarithromycin.
Answer: G
Macrolide antibiotics act by binding reversibly to the 50S subunit of the bacterial ribosome which is
therefore their primary cellular site of action.
A, B; C; D) Since macrolides act inside the bacterial cell, they must cross all the above mentioned
structures. These site are important for the pharmacokinetic of these drugs but they are not the site
of action of macrolides.
E, F) Macrolides do not affect mitochondria or ribosomes.
4.
A 49-year-old woman, who was on vacation in the south of Italy, presented with fever,
headache and a small, button like skin ulcer, 5 mm in diameter, with a black center. The
diagnosis of Mediterranean spotted fever was made and the woman was prescribed
doxycycline. Which of the following molecular actions most likely mediated the therapeutic
effect of the drug in the patient ‘s disease?
Correct Answer
D. Blockade of binding of aminoacyl-tRNA to bacterial ribosomes
Explanation
Learning objective: explain the mechanism of action of tetracyclines.
Answer: D
Mediterranean spotted fever (also called fiebre boutonneuse) is a disease caused by Rickettsia
conorii. Doxycycline is a tetracycline antibiotic that has became the drug of choice for most
rickettsial diseases, because of its efficacy, long half-life and very good oral bioavailability.
Tetracyclines bind reversibly to the 30s ribosomal subunit and block the access of aminoacyl-tRNA
to the acceptor side of the mRNA ribosome complex. This prevent the addition of amino acids to the
growing peptide chain and therefore inhibits bacterial protein synthesis
5.
A 28-year-old man recently diagnosed with Rocky Mountains spotted fever started a
treatment with doxycycline, two tablets daily. Which of the following is the primary site of
action of this drug?
Correct Answer
C. 30S subunit of bacterial ribosome
Explanation
Learning objective: identify the site of action of tetracyclines.
Answer: C
Tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome and block the access of
aminoacyl-tRNA to the acceptor side of the mRNA ribosome complex. This prevent the addition of
amino acids to the growing peptide chain and therefore inhibits bacterial protein synthesis
6.
A 32-year-old woman on a vacation trip in east Asia was diagnosed with acute
conjunctivitis. A topical treatment with chloramphenicol was able to heal completely the
disease. Which of the following molecular actions most likely mediated the therapeutic
efficacy of the drug in the patient’s disease?
Correct Answer
B. Blockade of transpeptidation reaction of protein synthesis
Explanation
Learning objective: explain the mechanism of action of chloramphenicol
Answer: B
Chloramphenicol enters the cell by facilitated diffusion and binds reversibly with the 50s ribosomal
subunit. In this site it prevents binding of the amino acid containing end of the aminoacyl tRNA to
the acceptor site of the 50S ribosomal subunit. Thus the peptide at the donor site cannot be
transferred to its amino acid acceptor, that is the transpeptidation reaction cannot occur. This
reaction is catalyzed by peptidyl transferase that is therefore indirectly inhibited by chloramphenicol.
7.
A 60-year-old man was recently diagnosed with osteomyelitis due to staphylococci that
turned out to be vancomycin resistant. The patient started a therapy with two antibiotics of
the streptogramin group. Which of the following is the primary site of action of these
antibiotics?
Correct Answer
A. The ribosomes
Explanation
Learning objective: identify the site of action of quinupristin and dalfopristin.
Answer: A
Quinupristin and dalfopristin are antibiotics of the streptogramin group. They bind to tow separate
sites on the 50S bacterial ribosome, forming a stable ternary complex. Thus they synergistically
interrupt protein synthesis.
8.
A 43-year-old woman recently diagnosed with urinary tract infection started a treatment
with trimethoprim-sulfamethoxazole. The inhibition of which of the following molecular
actions most likely mediated the therapeutic effect of the drug in the patient’s disease?
Correct Answer
C. Synthesis of bacterial purines and pyrimidines
Explanation
Learning objective: explain the mechanism of action of sulfonamides
Answer: C
Sulfonamides inhibit folic acid synthesis which in turn inhibits the synthesis of tetrahydrofolate.
Since tetrahydrofolate is needed for the synthesis of purines and pyrimidines, the synthesis of these
molecules is blocked.
A, B, D, E) Sulfonamides have no effect on the function of already formed DNA or NRA
9.
A 33-year-old man was admitted to the hospital with the admitting diagnosis of bacterial
pneumonia. Further exams indicated that pneumonia was due to Mycoplasma pneumonia
and a treatment with a bacteriostatic antibiotic was started. The given antibiotic most likely
belonged to which of the following classes?
Correct Answer
C. Macrolides
Explanation
Learning objective: list the main classes of bacteriostatic antibiotics.
Answer: C
Among the listed classes only macrolides are mainly bacteriostatic antibiotics. All beta-lactam drugs
(including cephalosporin and carbapenems) as well as aminoglycosides and fluoroquinolones are
bactericidal.
10.
A 34-year-old man recently diagnosed with streptococcal pharyngitis started a treatment
with amoxicillin, two tablets daily. Which of the following statements best explains a
prominent feature of the antibacterial action of this beta-lactam antibiotic?
Correct Answer
D. It continues as long as the concentration is greater that MBC
Explanation
Learning objective: describe the antibacterial action of beta-lactam antibiotics.
Answer: D
Beta-lactam antibiotic exert aa bactericidal effect which is time dependent, that is the killing
continues as long as the serum concentration of the drug is grater than the minimum bactericidal
concentration ()MBC).
A) All beta-lactam antibiotics are mainly bactericidal.
B) The antibacterial action of beta-lactam antibiotics is not concentration dependent.
C) Among beta-lactam antibiotics only carbapenems haves a postantibiotic effect.
E) The antibacterial action involves an activation, not an inhibition, of bacterial autolysins which are
able to destroy the bacterial cell wall.
11.
A 44-year-old man was admitted to the emergency room with the admitting diagnosis of
bacterial sepsis. Further exams indicated that Enterococcus faecium was the offending
pathogen and that the bacterium was vancomycin resistant. A treatment with linezolid was
started. Which of the following was most likely the site of action of this drug?
Correct Answer
D. The ribosomes
Explanation
Learning objective: identify the site of action of linezolid.
Answer: D
Linezolid binds to 50S ribosomal subunit at a site near to the 30 S ribosomal subunit so preventing
the formation of the initiation complex
12.
A 34-year-old woman recently diagnosed with salpingitis due to Bacteroides fragilis
started a treatment with a drug that is reduced by anaerobes to a highly reactive nitro radical
anion able to damage bacterial DNA. Which of the following drugs did the patient most likely
take?
Correct Answer
D. Metronidazole
Explanation
Learning objective: explain the mechanism of action of metronidazole.
Answer: D
Metronidazole is an antibiotic active against most microaerophile and anaerobic bacteria and
anaerobic protozoa. These microorganisms , unlike their aerobic counterparts, contains electron
transport components, called ferredoxins, that can donate electrons to metronidazole. This donation
forms a highly reactive nitro radical anion that damages bacterial DNA. and. The ultimate effect is
bactericidal.
13.
A 48-year-old man recently diagnosed with campylobacter diarrhea started a treatment
with an antibiotic that blocks the transfer of peptidyl tRNA from the acceptor site to the
peptidyl site of the bacterial ribosome. The given antibiotic most likely belonged to which of
the following classes?
Correct Answer
C. Macrolides
Explanation
Learning objective: explain the mechanism of action of macrolides
Answer: C.
Macrolide and lincosamides antibiotics block the translocation reaction, i.e. the transfer of peptidyl
tRNA from the acceptor site to the peptidyl site of the bacterial ribosome. The ultimate effect is
mainly bacteriostatic.
14.
A 42-year-old man recently diagnosed with mycoplasmal pneumonia started a treatment
with a fluoroquinolone, two tablet daily. Which of the following molecular actions most likely
mediated the therapeutic effect of the drug in the patient’s disease?
Correct Answer
B. Inhibition of relaxation of supercoiled bacterial DNA
Explanation
Learning objective: explain the mechanism of action of fluoroquinolones
Answer: B
Fluoroquinolones Inhibit bacterial DNA synthesis by blocking the following enzymes:
1) Topoisomerase II (also called DNA gyrase). The blockade prevent the relaxation of supercoiled
DNA which is required for normal transcription (prevalent mechanism in gram-negative bacteria)
2) Topoisomerase IV. The blockade interferes with separation of replicated chromosomal DNA
during cell division (prevalent mechanism in gram-positive bacteria).
15.
A 31-year-old woman, diagnosed with acute cystitis, started a treatment with
trimethoprim-sulfamethoxazole combination. Which of the following groups of steps shown
in the pathway below was most likely inhibited by that treatment?
Correct Answer
A. 1, 2, 3
Explanation
Learning objective: explain the mechanism of action of trimethoprim-sulfamethoxazole
combination.
Answer: A
By inhibiting dihydropteroate synthase, sulfonamides inhibit the formation of folate. By inhibiting
dihydrofolate reductase, trimethoprim inhibits the formation of dihydrofolate and tetrahydrofolate.
Inhibition of these consecutive steps in the formation of tetrahydrofolate constitute a sequential
blockade and results in antibacterial synergy.
B, C, D, E) The synthesis of DNA and RNA from already formed tetrahydrofolate are not inhibited by
trimethoprim sulfamethoxazole.