What is the best course of treatment for a patient with AmpC bacteremia, previously treated for Methicillin-Sensitive Staphylococcus Aureus (MSSA) with a recently removed chemoport, who is not responding to current antibiotics?

Management of AmpC Bacteremia Following MSSA Chemoport Infection

Switch immediately to a carbapenem (meropenem 1g IV q8h or ertapenem 1g IV q24h) for definitive treatment of AmpC-producing Enterobacteriaceae bacteremia, as carbapenems remain the drugs of choice for these organisms. 1

Immediate Antibiotic Management

Primary Treatment Options:

• Meropenem 1g IV every 8 hours is the preferred carbapenem for AmpC producers, providing reliable bactericidal activity 1, 2
• Ertapenem 1g IV every 24 hours is an acceptable alternative for non-Pseudomonas AmpC producers (Enterobacter, Serratia, Citrobacter) 1
• Imipenem 500mg IV every 6 hours is another carbapenem option if meropenem is unavailable 1

Carbapenem-Sparing Alternatives (if susceptibility confirmed):

• Cefepime 2g IV every 8 hours can be considered for AmpC producers if the isolate is susceptible, though clinical data are more limited 1, 3
• Cefepime showed non-inferior outcomes in AmpC bacteremia (aOR 0.65 for 30-day mortality vs carbapenems) 3
• Ceftazidime-avibactam 2.5g IV every 8 hours is active against AmpC producers and showed 80% clinical response rates, though it should be reserved for carbapenem-resistant organisms to preserve its activity 1, 4

Critical Diagnostic Steps

Source Control Assessment:

• Obtain repeat blood cultures immediately and every 48-72 hours until clearance is documented 5, 6
• Order urgent imaging (CT or MRI) to identify any residual infected hardware, abscess formation, or metastatic foci from the previous MSSA infection 7, 6
• Evaluate for retained suture material, pocket infection, or tunnel infection at the previous chemoport site 5

Endocarditis Evaluation:

• Obtain transthoracic echocardiography at minimum; transesophageal echocardiography is indicated if bacteremia persists >48 hours, fever continues, or any concern for endocarditis exists 5, 7, 6
• AmpC bacteremia following recent device removal carries risk for seeding cardiac structures 6

Treatment Duration

For Uncomplicated Bacteremia:

• Minimum 2 weeks IV therapy if blood cultures clear within 2-4 days, patient defervesces within 72 hours, no endocarditis, no metastatic infection, and no retained hardware 5, 7

For Complicated Bacteremia:

• 4-6 weeks IV therapy if any of the following: persistent bacteremia >48 hours, delayed clearance, metastatic infection identified, or concern for inadequate source control 5, 7
• If endocarditis confirmed, treat for 6 weeks from first negative blood culture 5, 7

Common Pitfalls to Avoid

• Do not use piperacillin-tazobactam for AmpC producers - AmpC β-lactamases hydrolyze piperacillin-tazobactam and are not inhibited by tazobactam 1
• Do not add aminoglycosides or rifampin to carbapenem therapy - combination therapy does not improve outcomes and increases nephrotoxicity 5, 7
• Do not assume adequate source control - the recent chemoport removal may have been incomplete or left residual infected tissue requiring surgical debridement 5, 6
• Do not delay repeat blood cultures - prolonged bacteremia ≥48 hours is associated with 39% 90-day mortality 7, 6

Risk Stratification

High-Risk Features Requiring Aggressive Management:

• Pitt bacteremia score >2 (each point increase carries aOR 1.21-1.33 for mortality) 3
• Persistent fever >72 hours on appropriate antibiotics 5
• Septic shock or pneumonia (where combination therapy may be beneficial) 1
• Immunocompromised state from cancer treatment 2