How should I manage a 63-year-old woman with a chronic tracheostomy who has a Stenotrophomonas maltophilia respiratory infection sensitive to levofloxacin but remains febrile after two days of therapy?

Management of Persistent Fever in S. maltophilia Respiratory Infection Despite Levofloxacin Therapy

Continue levofloxacin therapy beyond day 2 while conducting urgent diagnostic reassessment, as persistent fever at 48 hours does not indicate treatment failure for S. maltophilia respiratory infections, and levofloxacin demonstrates comparable efficacy to trimethoprim-sulfamethoxazole with a median time to defervescence of 5 days in critically ill patients. 1, 2, 3

Why Persistent Fever on Day 2 Does Not Indicate Treatment Failure

• Fever typically persists for 5 days in critically ill patients with serious infections, even with appropriate antimicrobial therapy, based on data from patients with hematological malignancies and severe infections 1
• Levofloxacin demonstrates bactericidal activity against S. maltophilia within 4 hours in vitro, but clinical defervescence takes substantially longer 4
• The median time from index culture to hospital discharge is actually shorter with levofloxacin (7 days) compared to TMP-SMX (9 days), suggesting adequate clinical efficacy 2

Immediate Diagnostic Reassessment Required

• Obtain repeat blood cultures and respiratory cultures to assess for treatment failure, superinfection, or alternative pathogens 5, 1
• Perform chest imaging (chest radiograph or CT) to evaluate for complications including empyema, lung abscess, or progression of pneumonia 5, 1
• Complete blood count with differential to identify neutropenia or worsening leukocytosis 1
• Comprehensive metabolic panel to assess for organ dysfunction 1
• Evaluate the tracheostomy site for local infection or obstruction that could be contributing to fever 6

Evidence Supporting Levofloxacin Continuation

• Levofloxacin demonstrates statistically similar mortality risk (aOR 0.76,95% CI 0.58-1.01) compared to TMP-SMX in a large multicenter study of 1,581 patients with S. maltophilia infections 2
• In lower respiratory tract infections specifically (n=1,452), levofloxacin showed lower adjusted odds of death (aOR 0.73,95% CI 0.54-0.98) compared to TMP-SMX 2
• A separate multicenter cohort of 371 patients found no significant differences in overall in-hospital mortality (52% vs 40%, p=0.113), 30-day mortality (28% vs 25%, p=0.712), or clinical cure rates (55% vs 64%, p=0.237) between TMP-SMX and levofloxacin 3
• Your isolate is confirmed susceptible to levofloxacin, which is critical as 16.4% of S. maltophilia isolates demonstrate levofloxacin resistance 7

When to Consider Switching Therapy

Switch from levofloxacin to TMP-SMX or alternative agents if:

• Clinical deterioration occurs (worsening respiratory status, hemodynamic instability, rising inflammatory markers) 1
• Fever persists beyond 5-7 days without any clinical improvement 1
• Repeat cultures grow resistant organisms or identify polymicrobial infection 5, 1
• Development of complications such as empyema or abscess requiring source control 5

Alternative Therapeutic Considerations

• TMP-SMX remains the traditional first-line agent and could be considered if clinical deterioration occurs, though evidence shows comparable outcomes to levofloxacin 2, 3
• TMP-SMX dosing would be based on the trimethoprim component at 15-20 mg/kg/day divided every 6-8 hours for serious infections 6
• Combination therapy is not routinely recommended but may be considered in severe cases with bacteremia 3
• Avoid empiric addition of vancomycin without specific indications, as this promotes resistance without clear benefit 1

Critical Monitoring Parameters

• Monitor for response to therapy at 48-72 hour intervals after any intervention 5
• Ensure adequate source control of the tracheostomy site 6
• Maintain adequate hydration and supportive care 1
• Acetaminophen can be used for symptomatic fever control, but do not use response to antipyretics to guide antibiotic decisions 1

Common Pitfalls to Avoid

• Do not assume treatment failure at 48 hours when the expected time to defervescence is 5 days in critically ill patients 1
• Do not switch antibiotics based solely on persistent fever without evidence of clinical deterioration or microbiologic failure 5, 1
• Do not ignore the possibility of non-infectious causes of fever including drug fever, though this is less likely given the acute presentation 5
• Recognize that the respiratory tract pH (~6.6) may affect fluoroquinolone activity, though levofloxacin maintains reasonable activity at this pH 8