A 76-year-old woman comes to the emergency department due to fever and burning with urination for 2 days and right-sided back pain for 1 day. Her temperature is 38.3 C (101 F), blood pressure is 110/80 mm Hg, pulse is 94/min, and respirations are 18/min. Examination is notable for right-sided flank tenderness to palpation. Urinalysis is positive for nitrites, leukocyte esterase, and bacteria. Urine and blood cultures are obtained, and the patient is started on antibiotic therapy. The next day, urine culture grows >100,000 colony-forming units/mL of Escherichia coli. The organism is found to have a methyltransferase that methylates ribosomal RNA. This enzyme most likely confers resistance to which of the following classes of antibiotics?
Common antibiotic resistance mechanisms | |
Penicillins |
|
Vancomycin |
|
Quinolones |
|
Aminoglycosides |
|
Tetracyclines |
|
Rifamycins |
|
ESBL = extended-spectrum beta-lactamase; PBP = penicillin-binding protein. | |
Aminoglycosides interfere with the aminoacyl binding site on the 30S ribosomal subunit. Binding of aminoglycoside causes the cell to misread mRNA and, as a result, it is unable to perform protein synthesis. An important mechanism of resistance to aminoglycosides is the methylation of the aminoglycoside-binding portion of the ribosome, which inhibits the ability of aminoglycosides to interfere with protein translation. Other common resistance mechanisms are the production of enzymes that inactivate the drug by altering its chemical structure or the production of an efflux pump that decreases the drug's intracellular concentration.
(Choices B and D) Carbapenems and penicillins function similarly to other beta-lactam antibiotics by inhibiting a family of enzymes responsible for cell wall construction. Resistance to both can occur through alteration of the antibiotic binding site on the enzyme; decreased permeability of the antibiotic into the cell wall; or production of beta-lactamases, which alter the antibiotic structure by cleaving protein bonds in the antibiotic and inactivating it.
(Choice C) Vancomycin is a glycopeptide antibiotic used to treat methicillin-resistant Staphylococcus aureus infections. It binds to D-alanine-D-alanine, thereby preventing peptidoglycan cell wall synthesis. Bacteria have been identified in which a D-alanine is replaced by a D-lactate, leading to vancomycin resistance.
(Choice E) Resistance to the quinolones occurs by alteration of the genes encoding for DNA gyrase and topoisomerase IV, development of an efflux pump, or alteration of the membrane diffusion channels used by the antibiotic.
Educational objective:
Aminoglycosides work by interfering with the 30S ribosomal subunit and causing the cell to misread messenger RNA, thereby halting protein synthesis. An important mechanism of resistance is the methylation of the aminoglycoside-binding portion of the ribosome, which inhibits the ability of aminoglycoside to interfere with protein translation.