What is the treatment for Achromobacter (Achromobacter denitrificans or Achromobacter xylosoxidans) infections?

Treatment of Achromobacter xylosoxidans/denitrificans Infections

For Achromobacter xylosoxidans infections, carbapenems (particularly meropenem or imipenem) should be the first-line treatment, as they demonstrate the highest in vitro susceptibility rates (>90%), with combination therapy reserved for severe infections or carbapenem-resistant isolates. 1

Antimicrobial Selection Algorithm

First-Line Therapy

• Meropenem or imipenem-cilastatin are the preferred agents based on superior in vitro activity (92.3% susceptibility) 1
• Piperacillin-tazobactam can be considered as an alternative for susceptible isolates 2
• Trimethoprim-sulfamethoxazole may be used in combination with beta-lactams for serious infections 2

Key Clinical Context

Achromobacter species are intrinsically resistant to multiple antibiotic classes, which significantly limits treatment options 3:

• Resistant to: Most cephalosporins, aztreonam, and aminoglycosides 3
• Increasing resistance to: Carbapenems due to multidrug efflux pumps and metallo-β-lactamases 3
• New β-lactamase inhibitors (like avibactam or vaborbactam) are not expected to overcome Achromobacter resistance mechanisms 3

Combination Therapy Considerations

• Use combination therapy (carbapenem + trimethoprim-sulfamethoxazole or carbapenem + fluoroquinolone) for severe infections, bacteremia, or respiratory tract infections in immunocompromised hosts 1, 2
• Prolonged therapy (minimum 4 weeks) is often required for adequate clinical and radiological response 2

Novel Treatment Options

Cefiderocol

• Cefiderocol has shown clinical efficacy in cystic fibrosis patients with A. xylosoxidans infections 4
• Important caveat: While clinical response occurred in 11 of 12 treatment courses, microbiologic relapse was observed in 11 of 12 cases, though without emergence of resistance 4
• Consider cefiderocol as salvage therapy for carbapenem-resistant isolates or treatment failures 3

Eravacycline

• Limited data exists, but eravacycline has been used as salvage therapy in select cases 3

Patient-Specific Risk Factors

High-risk populations requiring aggressive treatment include 1:

• Solid organ cancer patients (30.7% of cases)
• Heart failure patients (30.7% of cases)
• Patients with prior chemotherapy (associated with 66.7% mortality vs. 10% without chemotherapy)
• Patients with central venous catheters (46.1% of cases)
• Those with prior antibiotic exposure (53.8% of cases)

Source Control

Catheter removal is critical for intravascular catheter-related bacteremia, which represents 30.7% of cases 1. Primary bacteremia carries higher mortality (50% vs. 11.1% for other sources) 1.

Common Pitfalls

• Do not use monotherapy with cephalosporins or aminoglycosides due to intrinsic resistance 3
• Avoid short treatment courses: Prolonged therapy (≥4 weeks) is necessary for adequate response 2
• Do not assume new β-lactam/β-lactamase inhibitor combinations will work: Metallo-β-lactamases are not inhibited by avibactam or vaborbactam 3
• Recognize that microbiologic cure is difficult: Even with clinical improvement, microbiologic relapse is common, particularly with cefiderocol 4
• In non-cystic fibrosis patients with bronchiectasis or chronic lung disease, consider Achromobacter as a potential pathogen when standard therapy fails 5

Duration of Therapy

• Minimum 4 weeks for serious infections (pneumonia, empyema, bacteremia) 2
• Shorter courses (7-14 days) may be adequate for uncomplicated urinary tract infections with source control
• Monitor clinical and radiological response to guide duration 2