A previously healthy 24-year-old man is hospitalized due to 3 days of fever, chills, myalgia, and severe headache. The symptoms started on the last day of his camping trip in the Appalachian Mountains and have rapidly progressed. Temperature is 38.9 C (102 F), blood pressure is 100/56 mm Hg, and pulse is 120/min. On examination, the patient is lethargic and confused. There is no neck rigidity. The lungs are clear on auscultation and heart sounds are normal. The abdomen is soft and nontender. There is a prominent erythematous maculopapular rash on the distal forearms. No lymphadenopathy is present. The patient should be immediately initiated on a medication that targets which of the following?

Question

A previously healthy 24-year-old man is hospitalized due to 3 days of fever, chills, myalgia, and severe headache.  The symptoms started on the last day of his camping trip in the Appalachian Mountains and have rapidly progressed.  Temperature is 38.9 C (102 F), blood pressure is 100/56 mm Hg, and pulse is 120/min.  On examination, the patient is lethargic and confused.  There is no neck rigidity.  The lungs are clear on auscultation and heart sounds are normal.  The abdomen is soft and nontender.  There is a prominent erythematous maculopapular rash on the distal forearms.  No lymphadenopathy is present.  The patient should be immediately initiated on a medication that targets which of the following?

Quizplus · Accepted Answer

This patient developed fever, headache, myalgia, and a maculopapular rash while camping in the Appalachian Mountains, raising strong suspicion for Rocky Mountain Spotted Fever (RMSF). The causative pathogen is Rickettsia rickettsii, a weakly gram-negative, obligate intracellular bacterium. Transmission occurs following a tick bite from specific tick vectors (eg, American dog tick) present in the eastern and south-central United States and mountainous regions west of the Mississippi River. R rickettsii moves from the tick salivary glands to the human host after 6-12 hours of attachment. The pathogen enters vascular endothelial cells via endocytosis and subsequently lyses the endosome using specific virulence factors. It then replicates in the cytosol and nucleus of the host cell and spreads rapidly to adjacent cells via filopodia, leading to a lymphohistiocytic vasculitis. Manifestations begin with fever, headache, myalgia, and malaise followed 3-5 days later by a characteristic macular rash that becomes petechial over time. The rash typically begins on the ankles or wrists and spreads toward the center of the body (centripetally) as well as to the palms and soles. Thrombocytopenia frequently occurs as platelets are consumed due to widespread vascular injury. Antibiotic therapy is required to prevent progression and, potentially, death. First-line therapy is doxycycline, which inhibits protein synthesis by binding the 30s bacterial ribosomal subunit. (Choice A) Fluoroquinolones prevent DNA gyrase and topoisomerase from unwinding bacterial double-stranded circular DNA. Fluoroquinolones can be used to treat typhoid fever, a Salmonella infection that typically occurs in individuals who travel to developing nations. Symptoms include a step-wise fever, salmon-colored rose spots on the trunk, and intestinal bleeding/perforation. (Choice B) Trimethoprim-sulfamethoxazole inhibits bacterial replication by blocking 2 successive steps in bacterial folate metabolism: Sulfamethoxazole competes with para-aminobenzoic acid in the synthesis of dihydrofolic acid, and trimethoprim inhibits dihydrofolate reductase. (Choice D) Azole medications inhibit fungal ergosterol synthesis, which disrupts fungal cell membranes. Itraconazole can be used to treat pulmonary histoplasmosis, which usually causes subacute pneumonia with hilar or mediastinal lymphadenopathy. (Choice E) Penicillin medications inhibit peptidoglycan cross-linking, which disrupts bacterial (spirochetal) cell membranes. Penicillin is the first-line therapy for syphilis, a spirochetal infection that can present with fever and a diffuse, symmetric maculopapular rash that involves the palms and soles (secondary syphilis). However, patients typically have a mild (not high) fever and diffuse lymphadenopathy. (Choice F) Nucleotide and non-nucleoside reverse transcriptase inhibitors block viral reverse transcription. Although acute retroviral syndrome (early HIV infection) can present with a diffuse maculopapular rash and fever, patients also often have diffuse lymphadenopathy, a sore throat, and painful oral ulcers. In addition, RMSF is more likely in this case given this patient's recent camping trip. Educational objective: Rocky mountain spotted fever is a tick-borne illness due to Rickettsia rickettsii, a weakly gram-negative, obligate intracellular organism that has an affinity for vascular endothelial cells. Patients usually have nonspecific symptoms (eg, fever, malaise, myalgia) followed by a macular-petechial rash that begins on the ankles and wrists and spreads to the center of the body as well as to the palms and soles. Urgent treatment with doxycycline, an inhibitor of bacterial protein synthesis, is required.

A Previously Healthy 24-Year-Old Man Is Hospitalized Due to 3