A 68-year-old woman is evaluated in the emergency department for a 3-day history of fever,… — USMLE Step 3

A $68$ -year-old woman is evaluated in the emergency department for a $3$ -day history of fever, chills, right flank pain, and dysuria. Her medical history is significant for type $2$ diabetes mellitus, essential hypertension, and stage $3\text{a}$ chronic kidney disease with a baseline serum creatinine of $1.4 \text{ mg/dL}$ . Her daily home medications include metformin, lisinopril, empagliflozin, and atorvastatin.

Vital signs show a temperature of $38.9^\circ\text{C}$ ( $102.0^\circ\text{F}$ ), blood pressure of $92/58 \text{ mmHg}$ , pulse of $112/\text{min}$ , and respiratory rate of $18/\text{min}$ . Physical examination reveals dry mucous membranes and marked right costovertebral angle tenderness.

Laboratory studies show:
Leukocyte count: $16,500/\text{mm}^3$
Serum sodium: $138 \text{ mEq/L}$
Serum potassium: $4.8 \text{ mEq/L}$
Serum creatinine: $2.4 \text{ mg/dL}$
Blood urea nitrogen: $42 \text{ mg/dL}$
Serum bicarbonate: $18 \text{ mEq/L}$
Urinalysis: positive for nitrites, leukocyte esterase, and $>50 \text{ WBCs/hpf}$ .

The patient receives a $1\text{-L}$ bolus of intravenous lactated Ringer solution. Blood and urine cultures are obtained.

Which of the following are appropriate next steps in the pharmacologic management of this patient? (Select all that apply)

Discontinue home metformin therapyAnswer
Initiate intravenous ceftriaxone therapyAnswer
C
Continue home lisinopril therapy
D
Initiate intravenous ampicillin therapy
E
Administer oral sodium polystyrene sulfonate

Answer

The appropriate next steps are to discontinue home metformin therapy and initiate intravenous ceftriaxone therapy.

Discontinuing home metformin is critical because its renal clearance is severely impaired during acute kidney injury (AKI), heavily increasing the risk of life-threatening metformin-associated lactic acidosis, particularly in a patient with sepsis and hypoperfusion. Simultaneously, initiating intravenous ceftriaxone provides optimal empiric antimicrobial therapy for acute complicated pyelonephritis; it covers likely resistant gram-negative organisms (such as E. coli) and, unlike many other antibiotics, does not require renal dose adjustment, making it ideal for a patient with fluctuating renal function.

Step-by-Step Solution

Identify the primary acute diagnosis and its severity.

The patient has acute complicated pyelonephritis presenting with early sepsis.

The combination of fever, severe flank pain, dysuria, hypotension, and a strongly positive urinalysis points to a severe systemic infection originating from the urinary tract.

Evaluate the patient's current organ function, specifically renal status.

The patient has developed acute kidney injury (AKI) superimposed on chronic kidney disease.

Serum creatinine has acutely elevated from a baseline of 1.4 mg/dL to 2.4 mg/dL, secondary to sepsis-induced renal hypoperfusion and volume depletion.

Perform medication reconciliation to identify drugs that are now contraindicated.

Home metformin and lisinopril must be discontinued.

Metformin poses a high risk for lactic acidosis in the setting of AKI. Lisinopril impairs the compensatory efferent arteriolar vasoconstriction needed to maintain glomerular filtration, exacerbating both the AKI and the hypotension.

Select the optimal empiric antimicrobial therapy.

Intravenous ceftriaxone should be initiated.

Ceftriaxone adequately covers resistant gram-negative uropathogens and uniquely avoids the need for dose adjustment in fluctuating renal impairment.

Key Concept

In patients presenting with sepsis and acute kidney injury, simultaneous medication reconciliation (holding nephrotoxic or hemodynamically compromising home medications like ACE inhibitors and metformin) is as critical as initiating appropriate, non-nephrotoxic empiric antibiotics.

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