A 32-year-old man with HIV is diagnosed with pulmonary tuberculosis and started on a 4-drug combination therapy. On a follow-up visit 3 weeks later, he reports red urine and red staining of his contact lenses. A drug susceptibility test of his sputum isolates of Mycobacterium tuberculosis shows resistance to several antimycobacterial agents. Which of the following best explains the bacterial resistance to the drug responsible for this patient's current symptoms?

Question

A 32-year-old man with HIV is diagnosed with pulmonary tuberculosis and started on a 4-drug combination therapy.  On a follow-up visit 3 weeks later, he reports red urine and red staining of his contact lenses.  A drug susceptibility test of his sputum isolates of Mycobacterium tuberculosis shows resistance to several antimycobacterial agents.  Which of the following best explains the bacterial resistance to the drug responsible for this patient's current symptoms?

Quizplus · Accepted Answer

11ec160b_3bfe_5e35_9249_4dc6d1cbe821_MD0001_00 This patient with HIV has active pulmonary tuberculosis, typically treated with a 4-drug combination of a rifamycin (eg, rifampin, rifabutin), isoniazid, pyrazinamide, and ethambutol (RIPE therapy). The rifamycins commonly cause harmless red-orange discoloration of body fluids (urine, sweat, saliva, tears), which explains this patient's symptoms. They inhibit DNA-dependent RNA polymerase, thereby preventing transcription and leading to a deficiency of proteins necessary for mycobacterial survival. Structural alteration of this DNA-dependent RNA polymerase induces bacterial resistance. Unlike isoniazid, rifamycins are not specific to mycobacteria. (Choice A) Structural alteration of enzymes involved in DNA winding-unwinding would promote resistance to fluoroquinolones, drugs that bind and inhibit DNA gyrase in bacterial cells, causing fracture of the DNA chain. (Choice C) Antibiotics that act on the ribosome can be divided into those that act on the 50S subunit (eg, chloramphenicol, clindamycin, linezolid, macrolides) and those that act on the smaller 30S subunit (tetracycline, doxycycline, aminoglycosides). (Choice D) Decreased bacterial catalase-peroxidase activity is a mycobacterial response to isoniazid. Before it can inhibit mycolic acid synthesis, isoniazid must be converted to its active form by the mycobacterial catalase-peroxidase enzyme. (Choice E) Upregulation of beta-lactamase synthesis would cause bacterial resistance to beta-lactam drugs such as penicillins, aminopenicillins, cephalosporins, and monobactams. Infections caused by organisms expressing beta-lactamase require the addition of a beta-lactamase inhibitor (eg, clavulanic acid, sulbactam, tazobactam) or the use of a carbapenem. Educational objective: The rifamycins block the action of the bacterial DNA-dependent RNA polymerase, thereby inhibiting transcription. Resistance is acquired by modification of the rifampin binding site on the bacterial DNA-dependent RNA polymerase. Common side effects include hepatotoxicity, blood dyscrasias, and harmless red-orange discoloration of body fluids.

A 32-Year-Old Man with HIV Is Diagnosed with Pulmonary Tuberculosis