Nine days after undergoing an open right partial nephrectomy for localized renal cell carc… — USMLE Step 2 CK

Nine days after undergoing an open right partial nephrectomy for localized renal cell carcinoma, a 58-year-old man is assessed by the surgical team prior to planned discharge. His postoperative course was notable for a urinary tract infection diagnosed on postoperative day 2, which was effectively treated with oral trimethoprim-sulfamethoxazole based on susceptibility testing. Today, the patient reports that he feels completely well, has a robust appetite, and is eager to return home. However, his vital signs show a temperature of $39.4^\circ\text{C}$ ( $102.9^\circ\text{F}$ ), blood pressure of $128/82\text{ mm Hg}$ , pulse of $82\text{/min}$ , and respirations of $14\text{/min}$ . Oxygen saturation is $98\%$ on room air. Physical examination reveals a clean, well-approximated flank incision with no erythema, induration, or drainage. The lungs are clear to auscultation bilaterally. There is no costovertebral angle tenderness. The lower extremities show no edema or calf tenderness.

Laboratory studies show:

Test	Result
Leukocyte count	$8,500\text{/mm}^3$
Neutrophils	$60\%$
Eosinophils	$11\%$
Lymphocytes	$25\%$
Monocytes	$4\%$

Urinalysis is unremarkable. Which of the following is the most appropriate next step in management?

Discontinue trimethoprim-sulfamethoxazole and observeAnswer
B
Obtain blood cultures and start intravenous vancomycin and piperacillin-tazobactam
C
Order a computed tomography scan of the abdomen and pelvis
D
Perform duplex ultrasonography of the lower extremities
E
Order a chest radiograph and sputum culture

Answer

Discontinue trimethoprim-sulfamethoxazole and observe.

The correct approach is to discontinue trimethoprim-sulfamethoxazole and observe the patient. This presentation is classic for drug fever, a hypersensitivity reaction most commonly seen 1 to 2 weeks after initiating an offending medication (frequently antibiotics such as penicillins, cephalosporins, and sulfonamides). Key clinical clues include a very high fever in a patient who appears inappropriately well, often accompanied by relative bradycardia (a heart rate that is lower than expected for the degree of temperature elevation; normally, pulse increases by roughly

10\text{ beats/min}

for every

1^\circ\text{C}

of fever). Laboratory findings frequently reveal peripheral eosinophilia, as seen in this patient, though its absence does not rule out the condition. The appropriate management is to withdraw the suspected offending agent, which typically leads to defervescence within 48 to 72 hours.

Step-by-Step Solution

Analyze the timing of the patient's postoperative fever.

The new fever is occurring on postoperative day 9, which is 7 days after the initiation of trimethoprim-sulfamethoxazole.

The timing of postoperative fever helps narrow the differential diagnosis. Late fevers (occurring after day 7) are typically due to deep surgical site infections, central line infections, deep venous thrombosis, or drug fever.

Evaluate the clinical presentation in relation to the degree of fever.

The patient has a very high fever (

39.4^\circ\text{C}

) but appears remarkably well with no focal signs of infection (clean wound, clear lungs, normal urinalysis).

A severe infection causing such a high fever would typically make a patient appear toxic or ill. The dissociation between the high fever and the patient's benign clinical appearance is a major diagnostic clue.

Interpret the vital signs and laboratory results.

The patient exhibits relative bradycardia (pulse

82\text{/min}

despite high fever) and peripheral eosinophilia (

11\%

) without an overall leukocytosis.

Relative bradycardia and eosinophilia, combined with a benign clinical appearance 1-2 weeks after initiating an offending medication, strongly point to a diagnosis of drug fever.

Key Concept

Drug fever should be suspected in a patient who develops a high fever 1 to 2 weeks after starting a new medication (often an antibiotic), especially if they appear clinically well and exhibit relative bradycardia and peripheral eosinophilia.

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