A 43-year-old man comes to the emergency department due to 2 weeks of intermittent fevers, malaise, and headaches. He has a history of HIV and has not been taking his antiretroviral drugs recently. Five years ago, the patient spent a year in jail. Temperature is 38.2 C (100.8 F). Cerebrospinal fluid (CSF) analysis shows markedly elevated protein and low glucose, and CSF cultures grow Mycobacterium tuberculosis. Resistance testing shows the following: Which of the following best explains the resistance pattern seen in these bacteria?

Question

A 43-year-old man comes to the emergency department due to 2 weeks of intermittent fevers, malaise, and headaches.  He has a history of HIV and has not been taking his antiretroviral drugs recently.  Five years ago, the patient spent a year in jail.  Temperature is 38.2 C (100.8 F).  Cerebrospinal fluid (CSF) analysis shows markedly elevated protein and low glucose, and CSF cultures grow Mycobacterium tuberculosis.  Resistance testing shows the following:  Which of the following best explains the resistance pattern seen in these bacteria?

Quizplus · Accepted Answer

11ec160b_380c_b164_9249_b7cec1dc1800_MD0001_00 This patient with HIV has fever, headache, and central nervous system (eg, spinal fluid) culture growing Mycobacterium tuberculosis, consistent with M tuberculosis meningitis. Initial management is best accomplished through combination therapy with isoniazid (INH), rifampin, pyrazinamide, and either an injectable aminoglycoside or a fluoroquinolone. Streptomycin is one of the older drugs in the aminoglycoside family; therefore, bacterial resistance to this antibiotic is widespread, resulting in its current usage being limited mainly to the treatment of tuberculosis, plague, and tularemia. Like other aminoglycosides, streptomycin can be administered only parenterally. It works by interfering with the 16s rRNA of the bacterial 30S ribosomal subunit, thereby preventing bacterial protein synthesis. Mutations of the genes that encode ribosomal proteins are responsible for aminoglycoside resistance because they lead to modifications in the ribosomal binding sites for these drugs. Other resistance mechanisms to aminoglycosides include aminoglycoside-modifying enzymes (eg, transferases) and mutated porins. (Choice B) Structural alteration of enzymes involved in DNA winding-unwinding is the means by which many microorganisms become resistant to fluoroquinolone antibiotics. Fluoroquinolones inhibit the bacterial enzymes DNA gyrase (topoisomerase II) and topoisomerase IV. (Choice C) Structural alteration of enzymes involved in RNA synthesis is the mechanism through which organisms become resistant to rifampin. Rifampin inhibits the bacterial DNA-dependent RNA polymerase, thereby preventing the transcription of DNA into mRNA. (Choice D) Decreased activity of bacterial catalase-peroxidase is a mechanism of mycobacterial resistance to INH. Mycobacterial catalase-peroxidase is required for the initial enzymatic conversion of INH to its active metabolite within the mycobacterial cells; without this enzyme, INH is unable to inhibit mycobacterial mycolic acid synthesis. (Choice E) Increased activity of enzymes involved in cell wall polysaccharide synthesis is the means by which mycobacteria develop resistance to ethambutol. Ethambutol interferes specifically with mycobacterial peptidoglycan cell wall synthesis, possibly through inhibition of arabinosyl transferase. This drug is ineffective against organisms other than mycobacteria. Educational objective:

A 43-Year-Old Man Comes to the Emergency Department Due to 2