How to manage a 79-year-old patient with recurrent fevers unresponsive to doxycycline (tetracycline antibiotic) and Bactrim (sulfamethoxazole/trimethoprim)?

Management of Recurrent Fevers in a 79-Year-Old Patient Unresponsive to Doxycycline and Bactrim

For a 79-year-old patient with recurrent fevers unresponsive to doxycycline and trimethoprim/sulfamethoxazole (Bactrim), the recommended approach is to consider alternative antimicrobial therapy with fluoroquinolones (such as levofloxacin) combined with hydroxychloroquine, while simultaneously investigating for potential chronic infections, particularly Q fever.

Diagnostic Considerations

• Persistent fever despite treatment with doxycycline and trimethoprim/sulfamethoxazole suggests either:

  • Resistant organisms requiring alternative antimicrobial therapy 1
  • Chronic infection not adequately treated by the current regimen 1
  • Non-infectious causes of recurrent fever 2

• Essential diagnostic workup should include:

  • Blood tests: complete blood count, comprehensive metabolic panel, C-reactive protein in addition to ESR 3
  • Blood cultures to identify potential bacteremia 1
  • Serologic testing for Q fever, particularly if there's history of animal exposure 1
  • Imaging studies (ultrasound or CT) to rule out complications such as abscess formation, endocarditis, or vascular infection 3

Treatment Algorithm

Step 1: Evaluate for Q Fever

• Q fever should be strongly considered in elderly patients with recurrent fevers unresponsive to standard antibiotics 1
• If Q fever is suspected:
  • For acute Q fever: Consider extending doxycycline treatment to a full 14-day course at 100 mg twice daily 1
  • For chronic Q fever (endocarditis or vascular infection): Initiate doxycycline 100 mg twice daily plus hydroxychloroquine 200 mg three times daily for at least 18 months 1

Step 2: Consider Alternative Antimicrobial Regimens

• If Q fever is ruled out or treatment fails:
  • Consider fluoroquinolones (levofloxacin) as an alternative, which has shown efficacy against organisms resistant to doxycycline and trimethoprim/sulfamethoxazole 4
  • For suspected resistant organisms, consider combination therapy with a fluoroquinolone and another agent based on likely pathogens 5
  • For Stenotrophomonas maltophilia infections, consider doxycycline with aerosolized colistin 6

Step 3: Investigate Non-Infectious Causes

• If antimicrobial therapy continues to fail, evaluate for:
  • Drug fever (consider if fever resolves after discontinuation of medications) 7
  • Autoinflammatory disorders 2
  • Occult malignancy 3, 2

Special Considerations for Elderly Patients

• Elderly patients are at higher risk for complications from chronic infections and may present with atypical symptoms 1
• Monitor renal function closely when using antimicrobials, especially trimethoprim/sulfamethoxazole 1
• Be vigilant for potential drug interactions in elderly patients who may be on multiple medications 5
• Consider infectious disease consultation for patients with recurrent fevers unresponsive to multiple antibiotics 3

Red Flags Requiring Urgent Attention

• Fever >38°C with signs of sepsis requires immediate evaluation 3
• Persistent bacteremia or fevers lasting longer than 5-7 days after appropriate antimicrobial therapy may indicate a complicated infection requiring more aggressive management 3
• Consider hospital admission if symptoms worsen despite outpatient management 3

Follow-up Recommendations

• Schedule follow-up within 48-72 hours to assess response to any new therapy 3
• For patients diagnosed with Q fever, serologic monitoring is recommended after acute infection to assess possible progression to chronic infection 1
• If symptoms persist despite appropriate antibiotic therapy based on culture results, refer to infectious disease specialist 3