A 72-year-old man is evaluated in the intensive care unit for worsening abdominal pain, pr… — USMLE Step 2 CK

A $72$ -year-old man is evaluated in the intensive care unit for worsening abdominal pain, progressive distension, and high fever. He was admitted $8$ days ago for a complicated urinary tract infection and has been receiving intravenous ceftriaxone. Three days ago, he developed profuse, watery diarrhea, which abruptly ceased this morning. His temperature is $39.1^\circ\text{C}$ ( $102.4^\circ\text{F}$ ), blood pressure is $82/50\text{ mmHg}$ , and pulse is $128\text{/min}$ . Physical examination reveals a markedly distended, tympanic abdomen with diffuse tenderness and absent bowel sounds.

Laboratory studies show:

Test	Result	Reference Range
Leukocyte count	$34,000\text{/mm}^3$	$4,000-11,000\text{/mm}^3$
Serum creatinine	$2.9\text{ mg/dL}$	$0.6-1.2\text{ mg/dL}$ (Baseline: $1.0\text{ mg/dL}$ )
Serum lactate	$4.5\text{ mmol/L}$	$0.5-1.0\text{ mmol/L}$

A stool nucleic acid amplification test is positive for *Clostridioides difficile*. A portable plain abdominal radiograph demonstrates a transverse colon diameter of $10.5\text{ cm}$ , loss of haustral markings, and no evidence of free air.

Which of the following is the most appropriate next step in pharmacotherapy?

Enteral vancomycin and intravenous metronidazoleAnswer
B
Intravenous vancomycin and enteral metronidazole
C
Enteral fidaxomicin monotherapy
D
Intravenous meropenem
E
Conservative management with nasogastric decompression and intravenous fluids

Answer

The most appropriate next step in pharmacotherapy is the administration of enteral vancomycin and intravenous metronidazole.

This patient is presenting with fulminant *Clostridioides difficile* infection (CDI) complicated by an ileus and toxic megacolon. Fulminant CDI is characterized by severe systemic toxicity, manifesting as hypotension, shock, ileus, or megacolon. In the presence of a functional ileus—indicated by absent bowel sounds, abrupt cessation of diarrhea, and massive colonic dilation—orally administered antibiotics may not effectively transit to the colon. Therefore, the standard of care is combination therapy: high-dose enteral vancomycin (administered orally or via a nasogastric tube, frequently supplemented with vancomycin enemas) plus intravenous metronidazole. Intravenous metronidazole is uniquely beneficial because it is secreted directly from the bloodstream into the colonic mucosa, providing systemic coverage that complements the direct intraluminal effect of the enteral vancomycin.

Step-by-Step Solution

Assess the severity of the Clostridioides difficile infection.

The patient has fulminant disease, defined by hypotension (

82/50\text{ mmHg}

), shock (elevated lactate), severe leukocytosis (

34,000\text{/mm}^3

), and acute kidney injury.

Severity classification dictates the initial choice and route of antimicrobial therapy.

Identify complications modifying drug delivery.

The physical exam (absent bowel sounds, cessation of diarrhea) and radiograph (

10.5\text{ cm}

colonic dilation) indicate an ileus and toxic megacolon.

An ileus prevents orally administered medications from transiting effectively to the site of infection in the colon.

Select the appropriate targeted pharmacotherapy.

Dual therapy with enteral vancomycin (often given via nasogastric tube and supplemented by vancomycin enemas) combined with intravenous metronidazole is required.

IV metronidazole provides systemic delivery to the colonic mucosa, bypassing the ileus, while enteral vancomycin works intraluminally.

Key Concept

Management of fulminant Clostridioides difficile infection complicated by toxic megacolon

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