Multisystem Processes & Disorders

Candidemia: management and source control

Clinical Overview and When to Suspect Candidemia

— Persistent fever >72 h on broad-spectrum antibacterials without a clear source

— Central venous catheter (CVC), TPN, or hemodialysis access

— Recent abdominal surgery, anastomotic leak, recurrent GI perforation, or necrotizing pancreatitis

— Prolonged ICU stay (>7 days), mechanical ventilation, neutropenia, or chemotherapy

— Multifocal Candida colonization (urine + sputum + wound) in a critically ill patient

— Premature neonates and post–solid organ or stem cell transplant

Board pearl: Every blood culture growing yeast is never a contaminant — treat as true candidemia until proven otherwise, draw repeat cultures daily, and start an echinocandin empirically while species and susceptibilities pend.

CCS pearl: On the CCS case, ordering "blood culture × 2, ophthalmology consult, echocardiogram, remove central line, caspofungin IV" within the first simulated hour of a febrile ICU patient with yeast on Gram stain is the high-yield action sequence.

Definition: Bloodstream infection with Candida species, the 4th most common nosocomial BSI in US ICUs and associated with 30–40% crude mortality.

Epidemiology shift: C. albicans still leads but non-albicans species (C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and emerging C. auris) now exceed 50% in many US centers, driving fluconazole resistance.

When to suspect — think Candida in any patient with:

Risk score logic: Candida score ≥3 (TPN, surgery, multifocal colonization, severe sepsis) or a positive (1,3)-β-D-glucan in a high-risk ICU patient should prompt empiric antifungal therapy.

Why Step 3 cares: Candidemia is a transitions-of-care minefield — patients are diagnosed in the ICU, often need prolonged outpatient IV antifungals, mandatory ophthalmology follow-up, and line management decisions that span inpatient-to-outpatient settings.

Presentation Patterns and Key History

— Fever spikes temporally related to CVC flushing or TPN infusion

— Often C. parapsilosis (biofilm-forming, "the catheter Candida")

— Source is the line itself in ~70% of cases

— Recent abdominal surgery, anastomotic leak, perforated viscus, severe pancreatitis with necrosis

— Often C. albicans or C. glabrata

— Source is intra-abdominal — line removal alone will not cure

— Persistent fevers in a recovering neutropenic patient (after count recovery), elevated alkaline phosphatase, bull's-eye liver/spleen lesions on imaging

— Duration and spectrum of recent antibacterials (carbapenems, vancomycin, piperacillin-tazobactam are top drivers)

— TPN exposure, dialysis, recent surgeries, chemotherapy regimen, steroid dose/duration

— IV drug use (think C. albicans tricuspid valve)

— Prior azole exposure (predicts C. glabrata/krusei and fluconazole resistance)

— Healthcare exposure abroad or in long-term care (concern for C. auris, which requires contact isolation)

Key distinction: C. parapsilosis = catheter and TPN; C. glabrata = older, diabetic, prior fluconazole, GU source; C. krusei = intrinsic fluconazole resistance in heme malignancy on prophylaxis; C. auris = healthcare-associated, multidrug-resistant, mandatory public health reporting.

Nonspecific sepsis picture: Fever, chills, tachycardia, hypotension — indistinguishable from bacterial sepsis. Up to 40% are afebrile, especially elderly or immunosuppressed.

Catheter-associated candidemia:

Gut-translocation candidemia:

Disseminated/chronic disseminated (hepatosplenic) candidiasis:

Endocarditis presentation: New murmur, embolic phenomena, large vegetations on prosthetic valves or IV drug users using contaminated injection equipment.

Endophthalmitis: Floaters, scotoma, blurred vision — present in up to 16% and may be asymptomatic; mandates dilated exam.

Key history points to elicit:

Physical Exam Findings and Hemodynamic Assessment

— Fever, tachycardia, hypotension; lactate elevation tracks severity

— Apply qSOFA / SOFA and Surviving Sepsis criteria — septic shock from candidemia has higher mortality than bacterial shock

— Capillary refill, mottling, mental status — guide vasopressor and ICU triage decisions

— Erythematous macronodular lesions with pale centers, often on trunk and extremities — pathognomonic of disseminated candidiasis in neutropenic hosts; biopsy and culture

— Purpura fulminans–like lesions in severe sepsis

— Examine all CVC/PICC exit sites for purulence, erythema, tunnel tenderness

— Dilated fundoscopy by ophthalmology within 1 week of diagnosis for all non-neutropenic patients; in neutropenic patients, examine after count recovery (lesions may not appear until then)

— Chorioretinitis = white fluffy retinal lesions; endophthalmitis = vitreous extension, requires intravitreal therapy and vitrectomy consideration

— Auscultate for new murmurs — Candida endocarditis produces large, friable vegetations prone to embolization

— Look for Janeway lesions, Osler nodes, splinter hemorrhages, Roth spots

— Tenderness, peritoneal signs, surgical site evaluation — intra-abdominal source mandates source control

Step 3 management: A TTE is required in every candidemia patient; obtain TEE if TTE non-diagnostic, persistent candidemia despite source control, prosthetic valve, intracardiac device, or persistent fevers. Endocarditis dramatically changes duration and need for surgery.

Board pearl: Persistently positive cultures + new murmur + embolic stroke in a candidemic patient = Candida endocarditis → call cardiothoracic surgery; medical therapy alone is usually inadequate.

General/hemodynamic:

Skin findings (highly specific, low sensitivity):

Ocular exam (mandatory):

Cardiac:

Abdominal:

MSK/joint: Septic arthritis or osteomyelitis (vertebral, sternal) — palpate spine and prosthetic joints; Candida can seed bone weeks later.

Diagnostic Workup — Initial Labs, Imaging, and Biomarkers

— Draw ≥2 sets from peripheral sites; if CVC present, paired peripheral + line cultures help establish catheter as source (differential time-to-positivity ≥2 h favors line)

— Sensitivity only 50–70% — a negative culture does not rule out invasive candidiasis

— Once positive, repeat daily until clearance documented; Day 1 of therapy = first negative culture, not first positive

— MALDI-TOF on positive bottles gives species in hours

— Rapid PCR panels (T2Candida, BioFire) detect 5 common species directly from whole blood in 3–5 h, useful for early empiric tailoring

— Order fluconazole and echinocandin MICs on every isolate

— (1,3)-β-D-glucan: sensitivity 75–80%, specificity ~80%; useful in high-risk ICU patients with negative cultures; false positives with hemodialysis (cellulose membranes), IVIG, albumin, surgical gauze, β-lactams (amox-clav, pip-tazo)

— Mannan/anti-mannan antibody (less used in US)

— CXR baseline; CT abdomen/pelvis if intra-abdominal source suspected

— MRI or CT liver/spleen for chronic disseminated candidiasis (post-neutropenia fevers)

— TTE on all patients; TEE for high-risk features

Board pearl: A positive β-D-glucan in a stable ICU patient with risk factors but negative cultures still warrants empiric echinocandin while workup proceeds — don't wait for cultures to grow.

CCS pearl: Order "blood cultures q24h until negative" on day 1 — this is how you'll define total treatment duration on the simulation.

Blood cultures (cornerstone):

Species identification and susceptibility:

Biomarkers:

Supporting labs: CBC with diff (neutropenia worsens prognosis), CMP (renal/hepatic dosing), lactate, procalcitonin (often low — clue that it's not bacterial), coagulation panel.

Imaging:

Urinalysis and urine culture: Candiduria is usually colonization but may reflect ascending infection or hematogenous seeding in candidemia.

Diagnostic Workup — Advanced and Confirmatory Studies

— TTE first, ideally within 5–7 days of positive culture

— TEE indications: prosthetic valve, intracardiac device (pacemaker, AICD, LVAD), persistent candidemia >3 days on appropriate therapy, persistent fever, embolic events, suspected paravalvular abscess

— Vegetations >1 cm or any Candida prosthetic valve endocarditis → surgical consult

— Dilated fundoscopy by an ophthalmologist (not bedside) within 1 week

— In neutropenic patients, repeat after ANC recovers because lesions may be invisible during neutropenia

— Findings dictate duration (chorioretinitis extends therapy; endophthalmitis adds intravitreal voriconazole/amphotericin B and possible vitrectomy)

— MRI brain if focal neurologic signs (CNS candidiasis — switch to liposomal amphotericin B + flucytosine)

— MRI spine for back pain (vertebral osteomyelitis)

— Abdominal US/CT for hepatosplenic lesions; consider biopsy if persistent fevers post-neutropenia

— Echo of any prosthetic joint area; aspirate if pain/effusion

— CT abdomen/pelvis if recent surgery, perforation, pancreatitis — look for abscess, anastomotic leak

— HIDA or MRCP if biliary source suspected

— Send removed CVC tip for semiquantitative culture (>15 CFU = positive)

— If line cannot be removed (e.g., only access), consider antifungal lock therapy as adjunct, not substitute

Key distinction: Persistent candidemia >5 days on adequate therapy = look for occult deep source (endocarditis, suppurative thrombophlebitis, undrained abscess, retained catheter) — not antifungal failure alone.

Echocardiography:

Ophthalmologic exam:

Imaging for metastatic foci:

Source identification studies:

Catheter studies:

C. auris specifics: Notify lab to perform species ID — many automated systems misidentify C. auris as C. haemulonii or C. famata. Report to state/local health department and CDC under public health surveillance.

Risk Stratification and Management Logic

— Septic shock with risk factors

— Persistent fever on broad-spectrum antibiotics in ICU

— Multifocal Candida colonization + Candida score ≥3

— Positive β-D-glucan with compatible picture

— Don't wait for cultures in unstable patients

1. Start an echinocandin (caspofungin, micafungin, or anidulafungin) within hours — do not start fluconazole empirically in critically ill or azole-exposed patients

2. Remove the central venous catheter as soon as feasible (strong recommendation in non-neutropenic patients)

3. Source control — drain abscesses, debride necrotic tissue, replace infected hardware

4. Repeat blood cultures daily until clearance

5. Ophthalmology consult within 1 week

6. TTE for all; TEE if indicated

7. ID consultation — associated with lower mortality and better guideline adherence

— After 5–7 days of echinocandin, IF: clinically improved, follow-up cultures negative, isolate is fluconazole-susceptible, patient can tolerate PO, and no CNS/ocular/endocardial involvement

— C. glabrata: step down only if confirmed fluconazole-susceptible (high-dose 800 mg/day); often stay on echinocandin

— C. krusei: never use fluconazole — use echinocandin or voriconazole

— Uncomplicated candidemia: 14 days from first negative blood culture

— Endocarditis: ≥6 weeks post-valve surgery

— Endophthalmitis: 4–6 weeks

— Osteomyelitis: 6–12 months

— Chronic disseminated: months until imaging resolution

Step 3 management: The single highest-yield action that improves survival is prompt echinocandin start + line removal within 24–48 h — delay of either >24 h after positive culture independently increases mortality.

Empiric therapy triggers (IDSA 2016, still current):

First decisions on confirmed candidemia (the "Candida bundle"):

Step-down to fluconazole:

Duration:

Pharmacotherapy — First-Line Regimens

— Caspofungin 70 mg IV load → 50 mg IV daily

— Micafungin 100 mg IV daily (no loading dose; preferred in pediatrics)

— Anidulafungin 200 mg IV load → 100 mg IV daily (no hepatic/renal dose adjustment — best in organ dysfunction)

— Cover all Candida species except C. parapsilosis (intrinsically higher MICs — still works clinically, but if stable and isolate is fluconazole-S, transition to fluconazole)

— Excellent tolerability; main AE = transaminitis, infusion reactions (histamine release)

— Poor CNS, urinary, and ocular penetration — switch agents for these foci

— Fluconazole 800 mg (12 mg/kg) IV/PO load → 400 mg (6 mg/kg) daily for susceptible isolates in clinically stable, non-neutropenic patients without recent azole exposure

— Voriconazole for C. krusei or step-down in stable patients needing mold coverage; therapeutic drug monitoring (trough 1–5.5 mg/L); watch QTc, visual disturbances, hepatotoxicity, photosensitivity, CYP3A4 interactions

— Isavuconazole — alternative with less QT prolongation

— Liposomal amphotericin B 3–5 mg/kg IV daily — reserve for intolerance/resistance, CNS candidiasis, endophthalmitis, or pregnancy

— Toxicities: nephrotoxicity, hypokalemia/hypomagnesemia, infusion reactions (premedicate with acetaminophen ± diphenhydramine ± meperidine for rigors)

— Avoid amphotericin B deoxycholate (more toxic) when liposomal available

Board pearl: C. krusei = intrinsically fluconazole-resistant; C. glabrata = dose-dependent susceptibility, frequently resistant; C. auris = often resistant to fluconazole AND amphotericin — echinocandin is the workhorse for all three.

Echinocandins (first-line for all candidemia):

Azoles:

Polyenes:

Flucytosine: Adjunct for CNS or endocarditis (combined with ampho B); monitor levels, marrow toxicity.

Newer agents: Rezafungin (once-weekly echinocandin, FDA-approved 2023) and ibrexafungerp (oral glucan synthase inhibitor) — emerging roles, especially for outpatient transition.

Source Control — The Procedural Backbone

— Remove all CVCs in non-neutropenic candidemia — strongly recommended; mortality and duration of candidemia both decrease

— Time-to-removal ideally <24–48 h after first positive culture

— In neutropenic patients, source is more often gut-translocation, so line removal is individualized — remove if line is clearly the source (paired-culture differential time-to-positivity, exit-site infection, C. parapsilosis)

— If access is irreplaceable (limited venous options, pediatric oncology): exchange over wire is inadequate — place new line at new site; antifungal lock therapy as adjunct

— Tunneled catheters and ports: remove unless absolutely required; salvage attempts have high failure rates

— Percutaneous or surgical drainage of abscesses

— Repair of anastomotic leaks, debridement of infected pancreatic necrosis

— Antifungal therapy alone fails without drainage

— Valve replacement strongly recommended for native and prosthetic valve Candida endocarditis — medical therapy alone has >50% relapse

— Echinocandin or lipid amphotericin B + flucytosine; long-term suppressive fluconazole indefinitely if valve cannot be replaced

— Intravitreal voriconazole or amphotericin B injection

— Vitrectomy if vitreitis, macula-threatening lesions

— Surgical excision of involved vein if peripheral; anticoagulation considered for central vein thrombosis

— Two-stage exchange ideal; long-term suppression if retention required

— Relieve obstruction; remove/exchange Foley and stents

CCS pearl: On a simulated case, the order "Remove central venous catheter" must appear early — delaying it past 48 h is a common docked-points pitfall, equivalent to delaying source control in bacterial endocarditis.

Central venous catheter removal:

Intra-abdominal source control:

Endocarditis:

Endophthalmitis:

Suppurative thrombophlebitis:

Prosthetic device/joint infection:

Urinary tract candidiasis with obstruction:

Special Populations — Elderly, Renal, and Hepatic Impairment

— Higher baseline mortality; often afebrile presentation

— Polypharmacy increases azole interaction risk (warfarin, statins, DOACs, sulfonylureas, calcineurin inhibitors)

— Goals-of-care conversation early — candidemia mortality in frail elderly approaches 50%

— Watch for delirium from infection and from voriconazole (visual hallucinations, encephalopathy at high levels)

— Echinocandins: no dose adjustment — preferred agents

— Fluconazole: reduce dose by 50% if CrCl <50; give full dose after hemodialysis (dialyzable)

— Voriconazole IV: avoid in CrCl <50 due to cyclodextrin vehicle accumulation (use oral voriconazole instead) — Step 3 favorite distinction

— Liposomal amphotericin B: nephrotoxic; preload with normal saline 500 mL before and after each dose; monitor K+, Mg2+, creatinine daily

— Dialysis catheters that are infected source must be removed; coordinate temporary access with nephrology

— Caspofungin: reduce maintenance to 35 mg in moderate hepatic impairment (Child-Pugh B); avoid in severe

— Micafungin and anidulafungin: no hepatic adjustment

— Azoles: hepatotoxic — monitor LFTs weekly; voriconazole especially problematic

— Liposomal amphotericin B: safe hepatically

— Young trauma/burn ICU patients may underdose fluconazole; favor echinocandin

— Consider therapeutic drug monitoring for voriconazole, posaconazole

Step 3 management: A hemodialysis patient with candidemia: anidulafungin (no adjustment), remove tunneled HD catheter, place temporary non-tunneled access, replace tunneled line only after blood cultures clear ≥48–72 h — and never give IV voriconazole if you can avoid it.

Board pearl: Echinocandins are the "set-and-forget" antifungals for organ dysfunction — anidulafungin in particular has zero renal or hepatic dose adjustment.

Elderly:

Renal impairment / dialysis:

Hepatic impairment:

Critically ill / augmented renal clearance:

Special Populations — Pregnancy, Pediatrics, and Neutropenia

— Azoles are teratogenic at high or prolonged doses (especially first trimester) — fluconazole linked to craniofacial, skeletal, cardiac defects; voriconazole and posaconazole contraindicated

— Echinocandins: limited human data, Category C — use if benefit outweighs risk; micafungin most studied

— Liposomal amphotericin B: drug of choice for invasive candidiasis in pregnancy

— Single-dose oral fluconazole 150 mg for vaginal candidiasis is generally avoided in pregnancy now — use topical azoles

— Premature, very-low-birth-weight neonates are highest risk — empiric fluconazole prophylaxis used in select NICUs

— Amphotericin B deoxycholate or liposomal amphotericin B is preferred in neonatal candidemia due to higher CNS penetration; all neonates with candidemia need LP to rule out CNS involvement (frequent occult meningitis)

— Echinocandins (micafungin) approved >4 months; pediatric dosing weight-based

— Always remove umbilical and central catheters

— Echinocandin first-line; liposomal amphotericin B alternative

— Catheter removal individualized — gut translocation is often the source; aggressive removal less beneficial than in non-neutropenic

— Monitor for chronic disseminated (hepatosplenic) candidiasis post-engraftment — treat for months until imaging resolves

— Granulocyte recovery is the single most important prognostic factor

— Drug interactions are critical — azoles increase calcineurin inhibitor (tacrolimus, cyclosporine) and mTOR inhibitor (sirolimus) levels dramatically; reduce immunosuppressant doses 50–75% and monitor levels

— Echinocandins have minimal interactions — often preferred

Key distinction: Neonatal candidemia → LP mandatory, amphotericin B preferred. Adult candidemia → LP only if neuro signs, echinocandin preferred. This reversal is a high-yield exam point.

Pregnancy:

Neonates and pediatrics:

Neutropenic hosts (heme malignancy, HSCT):

Solid-organ transplant:

Complications and Adverse Outcomes

— Chorioretinitis / endophthalmitis (up to 16%) — vision-threatening

— Endocarditis — native or prosthetic, large vegetations, embolic stroke

— Hepatosplenic (chronic disseminated) candidiasis — post-neutropenic recovery, prolonged fever, elevated alk phos

— CNS candidiasis — meningitis, brain abscess, often in neonates or post-neurosurgery

— Vertebral osteomyelitis and discitis — back pain weeks-to-months later; MRI confirms

— Septic arthritis — native or prosthetic; aspirate

— Renal candidiasis — bilateral cortical microabscesses; fungal balls in collecting system causing obstruction

— Suppurative thrombophlebitis — persistently positive cultures despite line removal

— Amphotericin B: nephrotoxicity, K+/Mg2+ wasting, anemia, infusion reactions

— Voriconazole: visual disturbances, hepatotoxicity, photosensitivity (squamous cell carcinoma risk with chronic use), QTc prolongation, encephalopathy at high troughs, periostitis (fluoride accumulation) with prolonged use

— Fluconazole: QTc prolongation, hepatotoxicity, alopecia at high doses

— Echinocandins: transaminitis, infusion reactions, hypersensitivity

— Crude mortality 30–40%; attributable mortality 15–25%

— Predictors of death: septic shock, APACHE II >20, neutropenia, delayed antifungal start (>12–24 h), failure to remove catheter, C. tropicalis or C. glabrata species

— Prolonged ICU stay, prolonged hospitalization (~3 weeks median), high cost, need for OPAT, readmission for relapse if source not controlled

Board pearl: Persistent candidemia >5 days on appropriate therapy with adequate source control = look for endocarditis, suppurative thrombophlebitis, or undrained abscess — switching the antifungal is rarely the answer; finding the focus is.

Metastatic infection sites:

Pharmacologic complications:

Outcomes:

Health-system complications:

When to Escalate — ICU, Consult, and Triage

— Septic shock, vasopressor requirement, lactate >2

— Respiratory failure, multi-organ dysfunction

— High Candida score with hemodynamic instability

— Infectious Diseases: ID consult is associated with lower mortality, better guideline adherence, appropriate duration — order on every candidemia case

— Ophthalmology: dilated exam within 1 week (every case)

— Cardiology: TTE for all; TEE for high-risk features

— Cardiothoracic surgery: any Candida endocarditis, especially prosthetic valve

— General/transplant surgery: intra-abdominal source, abscess drainage

— Interventional radiology: percutaneous drainage of abscess, line replacement

— Vascular surgery: suppurative thrombophlebitis requiring excision

— Pharmacy: antifungal stewardship, drug interactions (especially in transplant)

— Most candidemia cases need inpatient management for initial echinocandin and line removal

— Outpatient parenteral antifungal therapy (OPAT) appropriate after source control, clinical improvement, ≥48–72 h of negative cultures, and arrangement of home health/infusion

— Step-down to oral fluconazole enables discharge — preferred when isolate susceptible

— Mortality is high; have a family meeting early in critically ill or elderly patients

— Palliative care consult for frail patients with multiple comorbidities

— Transfer to tertiary center for cardiac surgery in Candida endocarditis if local capability lacking

— C. auris cases may need infection control coordination and reporting

Step 3 management: Every candidemia case earns three mandatory consults — ID, ophthalmology, and cardiology (echo) — and one mandatory line-related action. Missing any of these on a vignette is the trap.

ICU admission criteria:

Mandatory consultations:

Triage decisions:

Code status and goals of care:

Transfer considerations:

Key Differentials — Other Fungal Bloodstream Infections

— HIV/AIDS with CD4 <100, transplant recipients, cirrhosis

— Encapsulated yeast on India ink, positive serum cryptococcal antigen (CrAg)

— Mandatory LP to rule out meningitis (most have CNS involvement)

— Treatment: liposomal amphotericin B + flucytosine induction → fluconazole consolidation/maintenance

— Ohio/Mississippi River valleys, bat/bird exposure

— Disseminated form in HIV, biologics (TNF-α inhibitors)

— Urine and serum Histoplasma antigen; bone marrow biopsy

— Treat with liposomal amphotericin B → itraconazole

— Hyaline mold or yeast-like organisms in profoundly neutropenic or HSCT patients

— Often resistant to echinocandins (Trichosporon breakthrough on echinocandins is classic)

— Require voriconazole or amphotericin B

— Neonates and adults on lipid-containing TPN through CVC

— Remove line, hold lipids, treat with amphotericin B or fluconazole

Key distinction: Yeast in blood culture with pseudohyphae on Gram stain = Candida; narrow-based budding without pseudohyphae + India ink positive = Cryptococcus; small intracellular yeasts in macrophages = Histoplasma. Morphology drives initial empiric choice while species ID pends.

Cryptococcemia (Cryptococcus neoformans):

Histoplasmosis (Histoplasma capsulatum):

Blastomycosis, Coccidioidomycosis: Endemic mycoses with characteristic geography and presentations; rarely truly "candidemia mimics" but on the differential of fungemia

Fusarium, Scedosporium, Trichosporon:

Pneumocystis jirovecii: Not bloodstream — but on the febrile-immunocompromised-host differential

Malassezia furfur fungemia:

Aspergillus: Rarely causes true fungemia; isolation from blood usually contaminant — but invasive aspergillosis is a major mimic of disseminated candidiasis in neutropenic hosts (galactomannan helps)

Key Differentials — Bacterial and Non-Infectious Mimics

— Same risk factors as candidemia (ICU, broad antibiotics, lines)

— Procalcitonin often elevated (vs. low/normal in candidemia)

— Gram stain differentiates; empiric coverage often must include both until cultures speciate

— Staphylococcus aureus, coagulase-negative staph, gram-negatives

— Same management principle — line removal, source control

— Echocardiogram for S. aureus bacteremia is also mandatory

— Viridans strep, S. aureus, enterococci — typical organisms

— Smaller vegetations than Candida; medical therapy often curative without surgery

— Persistent fevers, weight loss, multi-organ involvement

— AFB cultures, IGRA, chest imaging

— Often diagnosis of exclusion; eosinophilia, rash

— Resolves with stopping offending agent

— Pel-Ebstein pattern in Hodgkin, B-symptoms

— Refractory hypotension despite fluids/pressors — random cortisol, ACTH stim

— Persistent fever, cytopenias, hyperferritinemia, hypertriglyceridemia, hepatosplenomegaly

— Can mimic disseminated fungal infection

Board pearl: A patient with persistent fever on broad-spectrum antibiotics + central line + ICU stay + low procalcitonin = think Candida, draw fungal cultures, send β-D-glucan, and consider empiric echinocandin while workup proceeds.

Gram-negative bacteremia / septic shock:

CRBSI (catheter-related bloodstream infection) — bacterial:

Endocarditis (bacterial):

Disseminated tuberculosis / miliary TB:

Drug fever / antibiotic fever:

Hematologic malignancy / lymphoma fever:

Adrenal insufficiency in critical illness:

Transfusion reactions, DVT/PE, thyroid storm: Non-infectious causes of fever in ICU

Hemophagocytic lymphohistiocytosis (HLH):

Secondary Prevention, Discharge Plan, and Long-Term Management

— Most patients complete therapy as fluconazole 400 mg PO daily after IV step-down (if susceptible) — facilitates outpatient completion

— If on continued IV echinocandin or amphotericin: arrange OPAT with home infusion, weekly labs, ID follow-up

— Confirm 14 days from first negative blood culture for uncomplicated cases; longer for deep-seated infection

— Remove or minimize indwelling devices and TPN as soon as feasible

— Aggressive antimicrobial stewardship — narrow antibacterials, shorten courses

— In recurrent/relapsing disease, identify and eliminate persistent source (hidden abscess, retained hardware)

— Consider secondary prophylaxis (suppressive fluconazole) in:

— Prosthetic valve Candida endocarditis where valve cannot be replaced (lifelong suppression)

— Recurrent candidemia in ongoing immunosuppression

— High-risk surgical ICU patients with recurrent GI perforation (fluconazole or echinocandin)

— Liver, pancreas, small bowel transplant recipients (fluconazole or anidulafungin perioperatively)

— Allogeneic HSCT recipients during neutropenia (fluconazole or posaconazole)

— Very-low-birth-weight neonates in high-incidence NICUs (fluconazole)

— Azole drug interactions: warfarin (INR monitoring), statins (dose reduction or hold), DOACs, sulfonylureas (hypoglycemia), tacrolimus/cyclosporine (level monitoring), amiodarone/QTc-prolonging drugs

— Provide written list of contraindicated co-medications

— IV drug use counseling and treatment referral if relevant

— Diabetes optimization (glucose control reduces colonization)

— Decolonization not routinely recommended

Step 3 management: Discharge bundle = correct antifungal × correct duration + outpatient ID follow-up + ophthalmology re-exam at 4 weeks if initial findings + repeat echo if endocarditis + drug-interaction review + line-site healing check.

Discharge antifungal regimen:

Prevention of recurrence:

Primary prophylaxis populations:

Medication reconciliation at discharge:

Lifestyle/risk reduction:

Follow-Up, Monitoring, and Counseling

— Daily blood cultures until two consecutive negatives — defines Day 1 of treatment

— Daily CBC, BMP, LFTs while on antifungals; weekly thereafter

— Liposomal amphotericin B: daily K+, Mg2+, Cr; replace electrolytes proactively

— Voriconazole: trough at day 5, target 1–5.5 mg/L; LFTs weekly; ophthalmologic symptom screening

— Echinocandins: weekly LFTs

— QTc on baseline and follow-up ECG if on fluconazole, voriconazole, or other QT drugs

— ID clinic at 1–2 weeks post-discharge, then monthly until therapy complete

— Ophthalmology re-exam at 4 weeks if chorioretinitis present

— Repeat TTE at end of therapy for endocarditis; sooner if symptoms recur

— Surgical/IR follow-up for drains, line sites

— Return for recurrent fever, chills, new vision changes, back pain, new joint pain, weight loss, line-site redness/drainage

— Counsel on signs of relapse — may occur weeks to months later

— Post-ICU syndrome — cognitive, physical, psychological sequelae; refer to PT/OT and post-ICU clinic

— Nutritional rehabilitation if prolonged TPN or NPO

— Update influenza, pneumococcal, COVID-19, RSV (per ACIP)

— In transplant patients, coordinate live-vaccine timing with transplant team

— Explain that Candida is not "just a yeast" — it's a serious bloodstream infection

— Reinforce medication adherence and drug-interaction avoidance

— Discuss line care if a new long-term access is required

Board pearl: Day 1 of antifungal therapy = first day of negative blood cultures, not the day antifungals were started. Treat for 14 days from that date for uncomplicated candidemia — a recurring exam trap.

Inpatient monitoring:

Outpatient follow-up cadence:

Red flags for the patient (counsel before discharge):

Rehabilitation and recovery:

Vaccinations and health maintenance:

Patient education:

Ethical, Legal, and Patient Safety Considerations

— Line removal is a procedure with risks; ensure informed consent and alternative access planning

— CLABSI prevention bundles (hand hygiene, maximal barrier precautions, chlorhexidine, optimal site, daily review) are part of the institutional response — every candidemia case should trigger an infection-control review

— Document line-removal timing — delays >24–48 h are a quality metric and litigation risk

— Candida auris is reportable to state/local health departments and CDC in the US; immediate isolation precautions (contact + enhanced environmental cleaning with EPA List P disinfectants)

— Outbreak investigation if cluster identified

— Echocardiography (TEE) — sedation risks, esophageal injury

— Cardiac surgery for endocarditis — high-risk consent, especially in IV drug use with prior valve surgery; ethics consult may be needed for repeat valve replacement

— Pregnancy: discuss teratogenicity of azoles and offer alternatives; document shared decision-making

— Antifungal regimen errors at handoff (wrong drug, wrong dose, missed dose adjustments) — use medication reconciliation

— OPAT requires verified home setup, reliable infusion access, social support; readmission risk is high without these

— Communicate duration end-date clearly to PCP and outpatient ID

— Goals-of-care discussions in elderly/frail with high predicted mortality — early palliative consultation

— IV drug use and recurrent endocarditis — institutional policies vary; counsel on addiction treatment (buprenorphine, methadone) and offer multidisciplinary support; do not condition surgery on sobriety — this is increasingly viewed as discriminatory

— Antimicrobial stewardship — appropriate de-escalation, duration, and source-control documentation

— Quality reporting — CLABSI rates are publicly reported and tied to CMS reimbursement

Step 3 management: A patient with Candida endocarditis from IV drug use requesting a second valve replacement: provide medically appropriate care, offer addiction treatment, involve ethics if institutional resources are strained, and document multidisciplinary discussion — refusing surgery solely on the basis of ongoing substance use is not ethically defensible.

Patient safety — line management:

Mandatory reporting:

Informed consent considerations:

Transitions of care risks:

Ethical issues:

Health-system level:

High-Yield Associations and Rapid-Fire Facts

— C. albicans → gut translocation, surgical patients, general ICU

— C. glabrata → elderly, diabetics, prior fluconazole, GU source; dose-dependent azole resistance

— C. parapsilosis → catheters, TPN, neonates; biofilm-forming; higher echinocandin MICs — transition to fluconazole if susceptible

— C. tropicalis → neutropenia, hematologic malignancy; high virulence

— C. krusei → intrinsic fluconazole resistance; prior azole prophylaxis in heme malignancy

— C. auris → multidrug-resistant, healthcare-associated outbreaks, contact precautions, CDC notifiable

— Differential ≥120 minutes (line earlier than peripheral) = catheter source

— Septic shock, APACHE >20, delayed antifungal, retained line, neutropenia, C. glabrata/tropicalis

— Poor in urine, CNS, eye — switch to fluconazole or amphotericin for these foci

— Fluconazole loading dose always (12 mg/kg or 800 mg) on day 1

— Caspofungin 70 → 50 mg; reduce to 35 mg in moderate hepatic impairment

— Anidulafungin: no organ-failure adjustments

— Hemodialysis (cellulose), IVIG, albumin, surgical gauze, piperacillin-tazobactam, amoxicillin-clavulanate

— Uncomplicated: 14 days from first negative culture

— Endocarditis: ≥6 weeks post-surgery + lifelong suppression if no surgery

— Endophthalmitis: 4–6 weeks

— Hepatosplenic: months until imaging resolves

— Osteomyelitis: 6–12 months

Board pearl: "Yeast in the blood + recent abdominal surgery + persistent fever despite line removal" = look for an undrained intra-abdominal abscess — antifungals plus drainage, not antifungal escalation.

Species-risk associations:

Catheter time-to-positivity:

Mortality predictors:

Echinocandin gaps:

Dosing pearls:

β-D-glucan false positives:

Duration cheat sheet:

Three mandatory actions on every case: echinocandin, line removal, ophthalmology consult.

Three mandatory consults: ID, ophthalmology, cardiology.

Board Question Stem Patterns

Septic, intubated ICU patient on day 10 of pip-tazo and meropenem develops fever; blood cultures grow yeast at 24 h. Answer: start IV micafungin/caspofungin, remove CVC, order TTE, consult ophthalmology and ID; do not pick fluconazole first.

Patient improving on caspofungin × 5 days; blood cultures negative ×3 days; isolate is C. albicans, fluconazole-S. Answer: transition to fluconazole 400 mg PO daily to complete 14 days from first negative culture.

Heme malignancy patient on fluconazole prophylaxis develops candidemia. Answer: C. krusei — fluconazole-resistant; use echinocandin or voriconazole.

TPN patient with PICC develops candidemia; isolate is C. parapsilosis, fluconazole-S. Answer: remove PICC, transition from echinocandin to fluconazole given higher echinocandin MICs.

Persistent candidemia >5 days despite line removal, new murmur, vegetation on TEE. Answer: valve replacement + prolonged antifungal therapy.

Post-engraftment AML patient with fevers, elevated alk phos, target liver lesions on MRI. Answer: months of fluconazole until imaging resolves.

Third-trimester pregnant patient with candidemia. Answer: liposomal amphotericin B, avoid azoles.

Candidemic patient with floaters; fundus shows vitreous lesions. Answer: systemic + intravitreal voriconazole/amphotericin, consider vitrectomy.

Tunneled HD catheter, candidemia. Answer: anidulafungin/micafungin, remove tunneled catheter, temporary access until cultures negative.

Patient transferred from LTACH with multidrug-resistant Candida. Answer: echinocandin, contact precautions, notify public health, single room, dedicated equipment.

Key distinction across stems: The exam tests whether you (a) start an echinocandin promptly, (b) remove the line, (c) order ophtho/echo/ID, (d) tailor by species and site, and (e) treat for the right duration.

Stem 1 — Classic ICU candidemia:

Stem 2 — Step-down decision:

Stem 3 — C. krusei:

Stem 4 — C. parapsilosis on catheter:

Stem 5 — Endocarditis:

Stem 6 — Hepatosplenic candidiasis:

Stem 7 — Pregnancy:

Stem 8 — Endophthalmitis:

Stem 9 — Hemodialysis patient:

Stem 10 — C. auris outbreak:

One-Line Recap

Candidemia is a high-mortality bloodstream infection that demands prompt empiric echinocandin therapy, rapid central-line removal, aggressive source control of any deep focus, and mandatory ophthalmology and echocardiographic evaluation — with duration of 14 days from the first negative blood culture for uncomplicated cases and substantially longer for endocarditis, endophthalmitis, or osteoarticular involvement.

Board pearl: If a vignette gives you yeast in blood, the highest-yield single answer is almost always "start an echinocandin and remove the catheter" — every other step follows from those two actions, and every wrong answer choice on the exam is designed to distract you from doing both quickly.

Three nonnegotiable actions: start an echinocandin within hours, remove the central venous catheter within 24–48 h, get a dilated ophthalmologic exam within a week.

Three nonnegotiable consults: Infectious Diseases (mortality benefit), Ophthalmology (occult endophthalmitis), Cardiology (TTE for all, TEE for high-risk).

Species drives drug: echinocandin covers everyone empirically; C. krusei is fluconazole-resistant; C. parapsilosis prefers fluconazole step-down; C. glabrata needs susceptibility testing; C. auris is reportable and multidrug-resistant.

Duration anchor: Day 1 = first negative blood culture, not first dose of antifungal — treat 14 days from that day for uncomplicated candidemia, 6+ weeks for endocarditis post-surgery, months for hepatosplenic disease, and consider lifelong suppression when source cannot be controlled.