What is the recommended treatment for Burkholderia infections?

Treatment of Burkholderia Infections

Immediate Treatment Recommendations

For Burkholderia pseudomallei (melioidosis), initiate intensive phase therapy with ceftazidime 2g IV every 8 hours or meropenem 1g IV every 8 hours for 10-14 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 3-6 months eradication phase. 1

For Burkholderia cepacia complex infections, use trimethoprim-sulfamethoxazole as first-line therapy when susceptible, or alternatively ceftazidime, meropenem, or ceftazidime-avibactam based on susceptibility testing, typically in combination for severe infections. 2

Species-Specific Treatment Algorithms

Burkholderia pseudomallei (Melioidosis)

Intensive Phase (10-14 days minimum):

• First-line: Ceftazidime 50 mg/kg (up to 2g) IV every 6 hours 3
• Equally effective alternative: Meropenem 25 mg/kg (up to 1g) IV every 8 hours 3, 1
• Alternative: Imipenem 25 mg/kg (up to 1g) IV every 6-8 hours 3
• Duration extension: Extend intensive phase to 4-6 weeks for complicated infections including endocarditis, osteomyelitis, deep-seated abscesses, or neurologic involvement 3, 1

Eradication Phase (3-6 months):

• Standard regimen: TMP-SMX dosing based on weight: <40 kg: 160/800 mg every 12 hours; 40-60 kg: 240/1200 mg every 12 hours; >60 kg: 320/1600 mg every 12 hours, plus folic acid 0.1 mg/kg up to 5 mg daily 3
• Alternative for sulfonamide allergy: Amoxicillin/clavulanate 20/5 mg/kg every 8 hours (up to 1500/375 mg) plus doxycycline 100 mg every 12 hours 3
• CNS involvement: Add TMP-SMX 8/40 mg/kg (up to 320/1600 mg) IV/PO every 12 hours and extend duration to 4-8 weeks or longer 3

Adjunctive therapy consideration: G-CSF 300 mg IV for 10 days may be considered if septic shock is present 3

Burkholderia cepacia Complex

Antimicrobial selection based on severity:

• First-line (when susceptible): TMP-SMX 2
• Severe infections requiring combination therapy: Ceftazidime 2g IV every 8 hours plus an aminoglycoside or fluoroquinolone 2, 4
• Alternative monotherapy: Meropenem 1g IV every 8 hours 2, 4
• Additional options: Piperacillin-tazobactam 4.5g IV every 6 hours 4
• Clinical success rates: Ceftazidime-based regimens show 68.4-100% favorable outcomes; meropenem shows 66.7% success; piperacillin shows 75% improvement 4

Minocycline consideration: Shows 38% in vitro activity against B. cepacia complex strains, making it the most active single agent in susceptibility testing 5

Burkholderia mallei (Glanders)

Treatment regimen: Imipenem plus doxycycline for 2 weeks, followed by azithromycin plus doxycycline for 6 months 1

Critical Clinical Considerations

Catheter-Related Infections

• Catheter removal is essential for B. cepacia bloodstream infections to reduce treatment failure and improve survival 2, 1
• Remove catheter especially if bacteremia persists despite appropriate antimicrobials 1

Resistance Patterns and Drug Avoidance

• Never use vancomycin, teicoplanin, or daptomycin for Burkholderia infections due to intrinsic resistance 1
• Colistin does not cover Burkholderia species 3
• B. cepacia is intrinsically resistant to carbapenems due to metallo-β-lactamase, though meropenem paradoxically shows clinical efficacy 2
• Resistance mechanisms in B. pseudomallei include PenA β-lactamase overproduction (causing ceftazidime resistance), PBP3 deletion, and BpeEF-OprC efflux pump expression (causing TMP-SMX resistance) 6

Cystic Fibrosis-Specific Management

• Inhaled antibiotics: Administer twice daily using breath-enhanced open vent nebulizers at 6 L/min flow rate 2
• Equipment segregation: Use separate nebulizer equipment for B. cepacia-colonized patients versus Pseudomonas aeruginosa-colonized patients to prevent cross-contamination 2
• B. cepacia tends to colonize rather than cause invasive disease in CF patients, which should inform treatment duration decisions 2
• Susceptibility patterns differ between CF and non-CF patient isolates due to multiple antibiotic exposures 7

Infection Control Measures

• Contact precautions: Implement gown and gloves for all patient encounters 2
• Patient cohorting: Designate separate areas for B. cepacia-infected patients 2
• Transfer communication: Document and communicate B. cepacia status when transferring to other facilities 2
• Environmental screening: Perform surface screening in contact with colonized patients 2

Common Pitfalls to Avoid

• Do not rely on synergy testing: Antibiotic combination synergy is rarely demonstrated (only 1-15% of strains per combination) 5
• Do not use empiric vancomycin-based regimens for suspected gram-positive coverage if Burkholderia is in the differential 1
• Do not abbreviate eradication phase for B. pseudomallei even if clinical improvement occurs, as relapse rates are high with inadequate duration 3, 1
• Do not assume carbapenem resistance means clinical inefficacy for B. cepacia; meropenem shows paradoxical clinical benefit despite in vitro resistance mechanisms 2