What is the best course of action for a 54-year-old male with ESRD on hemodialysis, GPA, heart failure, and hypertension, presenting with fever, shaking chills, cough, and shortness of breath, on empiric antibiotics with vancomycin and cefepime?

Management of Persistent Fever in Hemodialysis Patient with Negative Infectious Workup

Primary Recommendation

Given the persistent low-grade fever for >72 hours despite 11 days of broad-spectrum antibiotics, negative extensive infectious workup including bronchoscopy, and the presence of a hemodialysis catheter, the hemodialysis catheter should be removed and replaced at a different anatomical site, as catheter-related bloodstream infection (CRBSI) remains the most likely source despite negative blood cultures. 1

Rationale for Catheter Removal

• The Infectious Diseases Society of America guidelines indicate that persistent fever beyond 2-3 days of appropriate antibiotics warrants catheter removal, even with negative cultures, as biofilm-associated infections may not be detected by standard blood cultures. 1

• The patient has received 48 hours off antibiotics with continued fever, and 11 total days of empiric therapy without resolution, meeting criteria for treatment failure. 1

• All blood cultures are negative, including one from the line, but this does not exclude catheter infection—biofilm bacteria may not be released into the bloodstream consistently. 1

• The elevated CRP (58.29) with normal ESR (16) points toward infection rather than GPA exacerbation, and the catheter remains the most probable occult source. 1

Immediate Management Steps

Catheter Management Algorithm

• Remove the existing hemodialysis catheter immediately and place a temporary (non-tunneled) catheter at a different anatomical site (femoral, internal jugular, or subclavian—whichever site was not previously used). 1, 2

• Send the catheter tip for culture using semi-quantitative or quantitative methods. 1

• Do not perform guidewire exchange in this case, as the patient has persistent symptoms and has failed empiric therapy. 1

• A new long-term hemodialysis catheter can be placed only after blood cultures obtained at the time of catheter removal remain negative for 48-72 hours. 1

Antibiotic Strategy

Restart empiric antibiotics with vancomycin PLUS gram-negative coverage immediately after obtaining blood cultures from the new catheter and a peripheral site (if accessible). 1, 2, 3

• Vancomycin dosing: 20 mg/kg (actual body weight) after each hemodialysis session, targeting pre-dialysis trough levels of 15-20 μg/mL. 1, 4, 5

• Gram-negative coverage: Use cefepime 2g after each dialysis session (given his current regimen) OR a third-generation cephalosporin, carbapenem, or β-lactam/β-lactamase combination based on local antibiogram. 1, 2, 6

• Duration: If cultures from the removed catheter are positive, treat for 4-6 weeks given the prolonged bacteremia (>72 hours of fever). 1

• If cultures remain negative: Continue antibiotics for 10-14 days from catheter removal, then reassess. 1

Critical Monitoring

• Obtain surveillance blood cultures 48-72 hours after catheter removal to document clearance. 1

• If blood cultures become positive after catheter removal, this confirms CRBSI and mandates the full 4-6 week treatment course. 1

• Perform transesophageal echocardiography (TEE) if S. aureus is isolated to evaluate for endocarditis, which would require 6 weeks of therapy. 1, 7

Addressing the Odontogenic Infection

The patient's poor dentition with broken and decayed teeth requires urgent dental extraction, as this represents another potential source of persistent bacteremia. 1

• Coordinate with oral surgery for extraction of all infected teeth as soon as the patient is medically stable. 1

• Odontogenic infections can cause persistent low-grade bacteremia that may not be captured by blood cultures, particularly in immunosuppressed patients on rituximab. 1

• Consider adding anaerobic coverage (metronidazole 500mg IV every 8 hours, adjusted for dialysis) if dental extraction is delayed and odontogenic infection is suspected as a contributing source. 1

Tuberculosis Evaluation

Proceed with repeat bronchoscopy with transbronchial biopsy for MTB PCR and histopathology, as agreed upon with the patient and pulmonology. 1

• The positive QuantiFERON, immunosuppression with rituximab, innumerable pulmonary nodules, and bilateral pleural effusions maintain TB on the differential despite one negative BAL MTB PCR. 1

• Transbronchial biopsy increases diagnostic yield compared to BAL alone and can identify granulomas suggestive of TB or GPA. 1

• Request that pathology perform MTB PCR on any existing tissue samples from prior procedures. 1

• Continue airborne precautions until TB is definitively excluded by repeat testing. 1

• If the second MTB PCR and biopsy are negative, TB becomes significantly less likely and empiric anti-tuberculous therapy can be deferred per patient preference. 1

Drug Fever Consideration

Drug fever is a reasonable consideration given 48 hours off antibiotics, but catheter removal should take precedence as CRBSI carries higher morbidity and mortality risk. 1

• If fever persists 72 hours after catheter removal with negative cultures and completion of the dental extractions, discontinue all non-essential medications and observe for defervescence. 1

• Vancomycin, cefepime, and antifungals are all potential causes of drug fever, but stopping antibiotics prematurely in an immunosuppressed patient with ESRD risks severe sepsis. 1

Common Pitfalls to Avoid

• Do not retain the catheter based on negative blood cultures alone—biofilm infections frequently have negative cultures but cause persistent fever. 1

• Do not perform guidewire exchange in this patient with treatment failure and persistent symptoms beyond 72 hours. 1

• Do not use vancomycin monotherapy if MSSA is eventually isolated—switch to cefazolin 20 mg/kg after dialysis, as vancomycin is associated with higher treatment failure rates for MSSA in hemodialysis patients. 1, 8

• Do not delay dental extraction—odontogenic infections in immunosuppressed patients can cause occult bacteremia and treatment failure. 1

• Do not empirically treat for TB without tissue diagnosis in this patient who has already had one negative MTB PCR and prefers definitive testing. 1

Antibiotic De-escalation Strategy

If methicillin-susceptible S. aureus is identified from catheter or blood cultures, immediately switch from vancomycin to cefazolin 20 mg/kg (actual body weight, rounded to nearest 500mg increment) after each dialysis session. 1, 8

• Vancomycin use for MSSA bacteremia in hemodialysis patients is associated with 3.5-fold higher odds of treatment failure compared to cefazolin. 8

• For vancomycin-resistant enterococci, use daptomycin 6 mg/kg after each dialysis session OR oral linezolid 600mg every 12 hours. 1

• If cultures remain negative after catheter removal and fever resolves, complete 10-14 days of antibiotics from the date of catheter removal. 1