How to manage a patient with a catheter-related bloodstream infection (CRBSI) due to Stenotrophomonas maltophilia that is resistant to trimethoprim-sulfamethoxazole (TMP-SMX)?

Management of TMP-SMX-Resistant Stenotrophomonas maltophilia CRBSI

Remove the catheter immediately and initiate alternative antimicrobial therapy with either levofloxacin, minocycline, or ceftazidime-avibactam plus aztreonam, as catheter retention in S. maltophilia CRBSI has unacceptably high failure rates due to biofilm formation. 1, 2

Immediate Catheter Management

The catheter must be removed for S. maltophilia CRBSI. 1, 2

• The IDSA guidelines explicitly recommend catheter removal for CRBSI caused by organisms with propensity for biofilm production, specifically naming Stenotrophomonas maltophilia alongside Pseudomonas and Acinetobacter species 1
• While salvage therapy may theoretically be attempted for S. maltophilia in "clinically stable patients" with limited vascular access, this applies only when the organism is susceptible to first-line agents 1, 2
• In your case with TMP-SMX resistance, catheter salvage is not recommended because alternative agents have inferior biofilm penetration and the failure rate becomes unacceptably high 1, 2
• For short-term catheters, removal is mandatory 1
• For long-term catheters or ports, removal is required when bloodstream infection persists >72 hours despite appropriate antibiotics 1, 2

Alternative Antimicrobial Options for TMP-SMX-Resistant Isolates

First-Line Alternatives

Levofloxacin is the preferred alternative to TMP-SMX for TMP-SMX-resistant S. maltophilia. 3, 4, 5

• Levofloxacin demonstrated statistically similar mortality compared to TMP-SMX in a large comparative effectiveness study of 1,581 patients (adjusted OR 0.76,95% CI 0.58-1.01) 5
• In lower respiratory tract infections specifically, levofloxacin showed lower mortality than TMP-SMX (adjusted OR 0.73,95% CI 0.54-0.98) 5
• Levofloxacin resistance rates are typically low (2.6-26% depending on geographic region) 6, 4
• Dosing: Standard levofloxacin 750 mg IV daily, though recent IDSA guidance suggests using it as part of combination therapy due to concerns about PK/PD breakpoints 3

Minocycline is the most reliably active agent against resistant S. maltophilia. 3, 7

• Minocycline demonstrated 92.7% susceptibility even among isolates nonsusceptible to levofloxacin and/or TMP-SMX 7
• Only 3 isolates in one study were resistant to all three agents (levofloxacin, TMP-SMX, and minocycline) 7
• Minocycline had the lowest MIC90 (4 mg/liter) of 12 agents tested against resistant S. maltophilia 7
• Dosing: Minocycline 100 mg IV every 12 hours 3

Novel Alternatives

Ceftazidime-avibactam plus aztreonam (CZA-ATM) is recommended by recent IDSA guidance for severe infections. 3

• This combination is suggested based on limited but promising clinical data for severe-to-moderate S. maltophilia infections 3
• Can be used as monotherapy (not requiring combination with other agents) 3

Cefiderocol is another novel option recommended by IDSA. 3

• Should be used as part of combination therapy 3
• Based on limited clinical data but favorable in vitro activity 3

Additional Options

• Tigecycline: Second most active agent after minocycline in susceptibility testing 7
• Polymyxin B (colistin): Demonstrated 91.2% susceptibility in one series, though concerns exist about nephrotoxicity 6
• Chloramphenicol: 85.7% susceptibility in some series but rarely used due to toxicity concerns 6, 4

Treatment Duration

Treat for 10-14 days after catheter removal if uncomplicated. 1, 2, 8

• Obtain repeat blood cultures 72 hours after initiating therapy to document clearance 1, 2, 8
• If bacteremia persists >72 hours despite appropriate antibiotics and catheter removal, extend therapy to 4-6 weeks as this suggests complicated infection 1, 8
• For complicated infections (endocarditis, suppurative thrombophlebitis, osteomyelitis), treat for 4-6 weeks 1, 8

Combination Therapy Considerations

Current IDSA guidance recommends combination therapy for severe S. maltophilia infections when using traditional agents. 3

• Combination therapy is recommended for SXT, levofloxacin, minocycline, or cefiderocol 3
• This recommendation is based on recent PK/PD studies questioning current clinical breakpoints 3
• Monotherapy with CZA-ATM is acceptable as an alternative 3
• Empirically, consider combining levofloxacin with minocycline or tigecycline until susceptibilities return 3, 6

Critical Pitfalls to Avoid

• Never attempt catheter salvage with antibiotic lock therapy for TMP-SMX-resistant S. maltophilia - the failure rate is unacceptably high and mortality risk increases 1, 2
• Never delay catheter removal beyond 72 hours if blood cultures remain positive despite appropriate antibiotics 1, 2, 8
• Never assume TMP-SMX susceptibility - resistance rates range from 14.3% to 25% depending on geographic region and hospital 6, 4
• Never use carbapenems or third/fourth-generation cephalosporins as monotherapy - S. maltophilia has intrinsic resistance to these agents (93.4% meropenem resistance, 52.3% ceftazidime resistance) 4
• Do not rely on empirical therapy alone - obtain susceptibility testing to guide definitive therapy, as resistance patterns vary significantly by institution 6, 4