A 32-year-old woman comes to the emergency department due to a mass under her right arm. She first noticed the mass 3 days ago and it has become progressively more swollen and painful. The patient has also had 5 days of high fever, chills, generalized muscle aches, and severe fatigue. She works for the city sanitation department and mentions there has been a recent surge in the rat population due to reduced frequency of trash removal. Temperature is 38.9 C (102 F), blood pressure is 110/70 mm Hg, pulse is 98/min, and respirations are 14/min. Physical examination reveals an enlarged, tender right axillary lymph node that is spontaneously draining purulent fluid. Several lymph nodes in the cervical, axillary, and inguinal regions are enlarged bilaterally. There are no other wounds or rashes. Blood cultures and an aspirate from a swollen axillary lymph node grow gram-negative bacilli. First-line treatment for this patient's infection most likely involves a drug with which of the following mechanisms of action?
Plague | |
Microbiology |
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Epidemiology |
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Manifestations |
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This patient with rapidly progressive systemic symptoms, generalized lymphadenopathy, and an enlarged, painful lymph node likely has bubonic plague, an infection caused by the gram-negative bacillus/coccobacillus Yersinia pestis. This highly virulent pathogen is endemic to areas of North and South America, Asia, Africa, and Russia. It is primarily transmitted by rodent fleas.
Manifestations begin with rapidly progressive fever, chills, weakness, and headache. Painful regional lymphadenopathy develops concurrently or within a few days; lymph nodes swell, develop overlying erythema, and often drain purulent fluid (buboes). When left untreated, plague progresses to sepsis with disseminated intravascular coagulation (DIC); the disease is sometimes called "black death" due to tissue necrosis from DIC.
The most common first-line treatment for plague is an aminoglycoside. This class of antibiotic prevents bacterial protein synthesis by binding with high affinity to the 30S ribosomal subunit. Aminoglycosides have particular potency against the Enterobacteriaceae family, Francisella tularensis, and Y pestis.
(Choice A) Trimethoprim-sulfamethoxazole blocks bacterial dihydrofolate formation and reduction, which inhibits the generation of purine nucleic acids for DNA synthesis and repair. Although trimethoprim-sulfamethoxazole can be used for plague, it is not a first-line therapy due to overall low efficacy (mortality rate 20-30%).
(Choice C) Penicillin agents inhibit the bacterial enzyme transpeptidase, which catalyzes the final cross-linking step in peptidoglycan elongation. Although penicillin antibiotics are often administered with gentamicin to treat infection with gram-positive organisms (penicillin disrupts the cell wall so gentamicin can enter the cytoplasm), Y pestis is a gram-negative pathogen; therefore, penicillins are not helpful.
(Choice D) Azole antibiotics inhibit the fungal enzyme 14 alpha-demethylase, which helps generate ergosterol. Ergosterol is a crucial component of the cell membrane of yeasts. Bacteria would be unaffected by inhibition of this fungal enzyme.
(Choice E) Vancomycin binds to the D-alanyl–D-alanine terminus of peptidoglycan, which blocks transpeptidase from elongating the peptidoglycan chain. Although vancomycin is sometimes used for streptococcal or staphylococcal adenitis, it has no efficacy against gram-negative pathogens.
Educational objective:
Yersinia pestis, the cause of bubonic plague, is transmitted primarily by rodent fleas. Manifestations include rapid-onset systemic symptoms (eg, high fever, chills, weakness, headache) and painful, purulent regional lymphadenitis. First-line treatment is with aminoglycosides, which block bacterial protein synthesis by binding to the 30S ribosomal subunit.