A 62-year-old man is admitted to the hospital with a 2-day history of fever, chills, and s… — USMLE Step 2 CK

A 62-year-old man is admitted to the hospital with a 2-day history of fever, chills, and severe right flank pain. He has a history of benign prostatic hyperplasia and recurrent urinary tract infections. His temperature is $39.1^{\circ}\text{C}$ ( $102.4^{\circ}\text{F}$ ), blood pressure is $92/60\text{ mmHg}$ , heart rate is $118/\text{min}$ , and respiratory rate is $20/\text{min}$ . Physical examination reveals marked right costovertebral angle tenderness.

Laboratory studies show a leukocyte count of $16,500/\text{mm}^3$ . Intravenous fluids are administered, and he is started empirically on intravenous vancomycin and piperacillin-tazobactam.

On hospital day 3, the patient's clinical status has significantly improved. He is afebrile with a blood pressure of $118/76\text{ mmHg}$ . Blood and urine cultures obtained on admission both grow *Enterobacter cloacae*.

The antimicrobial susceptibility report for the *Enterobacter cloacae* isolate is as follows:

Antimicrobial	Result
Ampicillin	Resistant
Ceftriaxone	Susceptible
Cefepime	Susceptible
Piperacillin-tazobactam	Susceptible
Meropenem	Susceptible
Ciprofloxacin	Resistant

Which of the following is the most appropriate next step in this patient's pharmacologic management?

A
Transition to intravenous ceftriaxone
Transition to intravenous cefepimeAnswer
C
Transition to intravenous meropenem
D
Continue intravenous piperacillin-tazobactam
E
Transition to oral nitrofurantoin

Answer

Transition to intravenous cefepime

The most appropriate next step is transitioning to intravenous cefepime. *Enterobacter cloacae* is a classic member of the SPACE/SPICE organisms, which possess a chromosomal, inducible AmpC beta-lactamase gene. When exposed to certain beta-lactam antibiotics—particularly third-generation cephalosporins like ceftriaxone—this gene becomes derepressed, leading to massive production of AmpC beta-lactamases and rapid clinical failure, despite the organism appearing susceptible on initial in vitro testing. Cefepime, a fourth-generation cephalosporin, is a poor inducer of AmpC and remains stable against hydrolysis by the enzyme. Therefore, it is the definitive treatment of choice for serious infections (such as pyelonephritis and bacteremia) caused by susceptible AmpC-producing organisms.

Step-by-Step Solution

Identify the infecting organism and its intrinsic resistance mechanisms.

The organism is Enterobacter cloacae, a known high-risk producer of inducible AmpC beta-lactamase (SPACE/SPICE organisms).

Recognizing AmpC producers is critical because their in vitro susceptibility to certain beta-lactams does not correlate with in vivo efficacy.

Evaluate the suitability of third-generation cephalosporins and piperacillin-tazobactam.

Both must be avoided. Third-generation cephalosporins induce AmpC production leading to treatment failure. Piperacillin-tazobactam has high failure rates for invasive AmpC infections.

Although the lab report marks them as 'Susceptible', clinical guidelines recommend against their use for invasive AmpC infections to prevent resistance emergence and relapse.

Select the narrowest-spectrum effective agent that is stable against AmpC beta-lactamase.

Cefepime is the most appropriate choice.

Cefepime (a fourth-generation cephalosporin) withstands AmpC hydrolysis and is the preferred definitive therapy. Meropenem is unnecessarily broad.

Key Concept

Definitive treatment of serious infections caused by high-risk AmpC beta-lactamase producers (e.g., Enterobacter cloacae) requires cefepime or a carbapenem; third-generation cephalosporins and piperacillin-tazobactam should be avoided despite apparent in vitro susceptibility.

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