What is the approach to managing fever in a critically ill ICU patient with a severe fungal infection and impaired renal function?

Approach to Fever in ICU with Severe Fungal Infection and Impaired Renal Function

In a critically ill ICU patient with severe fungal infection and impaired renal function, initiate an echinocandin (anidulafungin 200 mg loading dose then 100 mg daily, micafungin 100 mg daily, or caspofungin 70 mg loading then 50 mg daily) immediately, obtain at least two sets of blood cultures from different sites, perform fungal biomarker testing (1,3-β-D-glucan, mannan/anti-mannan), remove central venous catheters if present, and pursue aggressive source control while avoiding nephrotoxic agents. 1, 2, 3

Immediate Actions (Within 1-3 Hours)

Diagnostic workup must be completed rapidly but should not delay antifungal therapy:

• Obtain at least two sets of blood cultures (ideally 60 mL total) from different anatomical sites simultaneously, with one drawn peripherally and one through each vascular access device 4
• Measure lactate level immediately 4
• Order 1,3-β-D-glucan assay (grade 2B evidence), mannan and anti-mannan antibody assays (grade 2C evidence) when invasive candidiasis is suspected 4
• Initiate echinocandin therapy within the first hour of recognition—mortality approaches 100% in septic shock patients who do not receive adequate antifungal therapy within 24 hours 1, 2

Antifungal Selection in Renal Impairment

Echinocandins are the preferred first-line agents and require no dose adjustment for renal dysfunction:

• Anidulafungin: 200 mg loading dose Day 1, then 100 mg daily 1, 2, 3
• Micafungin: 100 mg daily (no loading dose required) 1, 2, 3
• Caspofungin: 70 mg loading dose Day 1, then 50 mg daily 1, 2, 3

All three echinocandins demonstrate equivalent efficacy and mortality outcomes in septic shock, with prompt initiation reducing mortality by as much as 50% 2

Avoid fluconazole as first-line therapy in critically ill patients with septic shock, even without recent azole exposure—echinocandins are superior in this population 2, 3

If echinocandins are contraindicated or unavailable, liposomal amphotericin B is the preferred alternative in renal impairment:

• Liposomal amphotericin B can be safely used in critically ill patients with impaired renal function, showing minimal impact on renal function and avoiding the nephrotoxicity of conventional amphotericin B 5, 6
• Dosing: 3-5 mg/kg/day for empiric therapy in febrile neutropenic patients 7
• In patients with elevated creatinine >1.5 mg/dL at treatment initiation, liposomal amphotericin B resulted in an absolute decrease of creatinine by 1.08 mg/dL, with 50% achieving normal renal function 5

Source Control and Catheter Management

Central venous catheter removal is mandatory in non-neutropenic patients with candidemia:

• Remove all central venous catheters and culture a 5-7 cm intracutaneous segment to document the source of bacteremia/fungemia 4, 1
• With short-term catheters, culture both the intracutaneous segment and tip; with pulmonary artery catheters, culture both the introducer and the catheter 4
• If tunnel infection, embolic phenomenon, vascular compromise, or septic shock is present, remove the catheter immediately and insert a new one at a different site 4

Biomarker-Guided Approach

Use procalcitonin (PCT) and C-reactive protein (CRP) strategically based on pretest probability:

• If bacterial infection probability is low-to-intermediate with no clear focus, measure PCT or CRP in addition to bedside clinical evaluation 4
• If bacterial infection probability is high, do not measure PCT or CRP to rule out bacterial infection—proceed directly with empiric therapy 4
• PCT may guide duration and cessation of antibiotic therapy in critically ill patients 4

Imaging and Additional Diagnostics

Perform imaging studies promptly to confirm infection source, balancing transport risks:

• Bedside ultrasound should be prioritized to avoid patient transport risks 4
• CT imaging is particularly valuable for detecting posterior-inferior lung base disease and small nodular/cavitary lesions in immunocompromised patients 4
• For suspected pneumonia or upper respiratory symptoms, test for viral pathogens using nucleic acid amplification test panels 4
• Test for SARS-CoV-2 by PCR based on community transmission levels 4

Urinary Tract Evaluation

For febrile ICU patients with pyuria and suspected urinary tract infection:

• Replace the urinary catheter and obtain urine cultures from the newly placed catheter 4
• The urinary tract is generally unimportant as a primary source of infection in most ICU patients 8

Hemodynamic Management

If hypotension or lactate ≥4 mmol/L is present:

• Administer 30 mL/kg crystalloid within 3 hours 4
• Apply vasopressors within 6 hours for hypotension not responding to initial fluid resuscitation, targeting MAP ≥65 mmHg 4
• Measure central venous pressure (target ≥8 mmHg), central venous oxygen saturation (target ≥70%), and remeasure lactate if initially elevated 4

Duration of Antifungal Therapy

Continue echinocandin therapy for a minimum of 2 weeks after documented clearance of Candida from the bloodstream AND resolution of clinical signs and symptoms:

• For empiric therapy in patients who improve clinically, continue for 2 weeks (same as documented candidemia) 1, 2
• For chronic disseminated candidiasis, continue antifungal therapy until lesions resolve on repeat imaging, typically several months 1
• Premature discontinuation before completing the full 2-week course after blood culture clearance significantly increases relapse risk 2

Monitoring and Follow-up

Perform dilated funduscopic examinations to rule out endophthalmitis in all patients with candidemia 1, 3

For persistent candidemia despite appropriate therapy:

• Consider imaging of the genitourinary tract, liver, and spleen 1
• Reassess for inadequate source control or need for re-operation 4

Common Pitfalls to Avoid

Delaying antifungal therapy while awaiting culture results in patients with septic shock and risk factors for invasive candidiasis significantly increases mortality—each hour delay is associated with measurable mortality increase 4, 2, 3

Empiric therapy based solely on colonization with Candida species is inadequate—risk stratification tools and biomarkers should guide decision-making 4, 1

False-positive reactions with fungal biomarkers can occur with colonization alone, requiring clinical correlation 4

Blood cultures are negative in up to 50% of invasive candidiasis cases, necessitating empiric treatment based on clinical suspicion and risk factors 4, 3

Failure to remove central venous catheters in non-neutropenic patients with candidemia is associated with treatment failure and increased mortality 1