A 58-year-old man is evaluated on hospital day 3 for persistent fever. He was admitted with fever, severe left flank pain, and dysuria, and was diagnosed with acute complicated pyelonephritis. At that time, empiric therapy with intravenous ceftriaxone was initiated.
Today, he reports continued flank pain and malaise. His temperature is (), blood pressure is , pulse is , and respiratory rate is . Physical examination reveals persistent left costovertebral angle tenderness.
Blood cultures drawn on admission are now positive for *Enterobacter cloacae*. The antimicrobial susceptibility report is as follows:
| Antimicrobial Agent | Interpretation |
|---|---|
| Ampicillin | Resistant |
| Cefazolin | Resistant |
| Ceftriaxone | Susceptible |
| Cefepime | Susceptible |
| Ciprofloxacin | Susceptible |
| Meropenem | Susceptible |
| Piperacillin-tazobactam | Susceptible |
Which of the following is the most appropriate next step in pharmacotherapy?
- AContinue intravenous ceftriaxone
- BTransition to intravenous meropenem
- CAdd intravenous vancomycin
- Transition to intravenous cefepimeCevap
- ETransition to oral ciprofloxacin
Cevap
Transition to intravenous cefepime is the most appropriate next step to effectively treat this AmpC-producing pathogen while adhering to antimicrobial stewardship.
The correct answer is to transition to intravenous cefepime. This patient has bacteremic pyelonephritis caused by *Enterobacter cloacae*. *Enterobacter* species are part of the 'SPACE' group (Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter) of Gram-negative bacilli, which possess a chromosomally encoded, inducible AmpC beta-lactamase. When exposed to third-generation cephalosporins (such as ceftriaxone), these bacteria can rapidly upregulate AmpC production. This leads to clinical treatment failure and in vivo resistance, despite the organism appearing susceptible on initial in vitro testing. Therefore, ceftriaxone should never be used for invasive *Enterobacter* infections. According to major infectious disease guidelines, intravenous cefepime (a fourth-generation cephalosporin) is the preferred definitive therapy. Cefepime is highly stable against AmpC hydrolysis, provides excellent targeted coverage, and spares the use of carbapenems, perfectly aligning with the principles of antimicrobial stewardship.
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Infections caused by SPACE organisms (e.g., Enterobacter) with inducible AmpC beta-lactamases should be treated with cefepime or carbapenems, avoiding third-generation cephalosporins even if they appear susceptible in vitro.
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