A 31-year-old man comes to the emergency department with a 2-week history of fever, night sweats, and productive cough. He has also had a 5-kg (11-lb) weight loss. He has no other medical problems. The patient is a software engineer who moved to the United States from Uzbekistan 15 years ago. He takes no medications and has no known drug allergies. His temperature is 38.3 C (101 F), blood pressure is 110/80 mm Hg, pulse is 94/min, and respirations are 18/min. He weighs 60 kg (132.3 lb). Pulse oximetry shows 94% on room air. Chest-x ray reveals a cavitary lesion on the right. Sputum culture is obtained. When exposed to drug A, isolates of the pathogen growing in culture quickly become less resistant to decoloration with an acid-alcohol agent and stop proliferating. Which of the following is drug A most likely to be?

Question

A 31-year-old man comes to the emergency department with a 2-week history of fever, night sweats, and productive cough.  He has also had a 5-kg (11-lb) weight loss.  He has no other medical problems.  The patient is a software engineer who moved to the United States from Uzbekistan 15 years ago.  He takes no medications and has no known drug allergies.  His temperature is 38.3 C (101 F), blood pressure is 110/80 mm Hg, pulse is 94/min, and respirations are 18/min.  He weighs 60 kg (132.3 lb).  Pulse oximetry shows 94% on room air.  Chest-x ray reveals a cavitary lesion on the right.  Sputum culture is obtained.  When exposed to drug A, isolates of the pathogen growing in culture quickly become less resistant to decoloration with an acid-alcohol agent and stop proliferating.  Which of the following is drug A most likely to be?

Quizplus · Accepted Answer

11ec160b_3bfe_fa77_9249_b13c85889afc_MD0001_00 Isoniazid is an antimicrobial agent that is active only against mycobacteria. Its specificity is derived from its inhibition of mycolic acid synthesis. Mycolic acids form long branched-chain fatty acids in the outer portion of the mycobacterial peptidoglycan cell wall; they are essential for proper cell wall structure and virulence factor synthesis (eg, sulfatides, wax D, cord factor). If mycobacteria are unable to synthesize mycolic acids, they cannot create proper cell walls or divide to form new cells. Mycolic acids in the cell wall cause mycobacteria to be acid-fast as they retain the carbolfuchsin dye and resist decoloration by an acid-alcohol decolorizing agent. (Choice A) The fluoroquinolones (eg, ciprofloxacin) are emerging as new components of the multi-drug regimen used to treat tuberculosis. They inhibit DNA gyrase, leading to fractures in the bacterial chromosome and an inability to code for proteins necessary for survival. Fluoroquinolones would not have an immediate effect on the acid-fastness of mycobacteria. (Choice C) Rifampin is an essential component of the multi-drug regimen used to treat active tuberculosis. Rifampin halts bacterial protein synthesis by inhibiting bacterial DNA-dependent RNA polymerase, thereby preventing DNA transcription into mRNA. Rifampin would inhibit mycobacterial growth in an in vitro culture, but it would not cause the mycobacteria to lose their acid-fastness. (Choice D) Streptomycin is an aminoglycoside that inhibits the bacterial 30S (small) ribosomal subunit, thereby halting protein synthesis. Mycobacterial cell growth is restricted and eventually cell death results. However, the acid-fastness of the organism is not affected. Streptomycin is also indicated in the treatment of plague (caused by Yersinia pestis) and tularemia (caused by Francisella tularensis). (Choice E) Vancomycin binds to D-alanyl-D-alanine residues, inhibiting polymerization and cross-linking of the glycopeptides forming the cell wall of gram-positive bacteria (not mycobacteria). Educational objective: Isoniazid is an antimycobacterial agent that specifically inhibits the synthesis of mycolic acids, which are essential components of the unique mycobacterial peptidoglycan cell wall. Without mycolic acids, the mycobacteria lose their acid-fastness and become unable to synthesize new cell walls or multiply. __________ References: Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis. (http://www.ncbi.nlm.nih.gov/pubmed/12164478)

A 31-Year-Old Man Comes to the Emergency Department with a 2-Week