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Candidemia
Cardiovascular Presentations
Abdominal aortic aneurysm
Acute coronary syndrome (NSTEMI)
Acute coronary syndrome (STEMI)
Acute decompensated heart failure
Acute limb ischemia
Acute mesenteric ischemia
Aortic dissection
Aortic stenosis
Atrial fibrillation and flutter
Bradyarrhythmia and heart block
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Deep vein thrombosis
Myocarditis
Pericarditis
Pulmonary embolism
Stable angina
Superficial thrombophlebitis
Superior vena cava syndrome
Supraventricular tachycardia
Syncope (cardiogenic)
Unstable angina
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Respiratory Presentations
Acute bronchitis
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Aspiration pneumonia
Asthma exacerbation
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Community-acquired pneumonia
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Croup
Croup (laryngotracheobronchitis)
Epiglottitis
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Hospital-acquired pneumonia
Pleural effusion
Pneumothorax (traumatic)
Pulmonary contusion
Spontaneous pneumothorax
Neurological Presentations
Bell's palsy
Benign paroxysmal positional vertigo
Brain abscess
Cauda equina syndrome
Cervical radiculopathy
Concussion (mild traumatic brain injury)
Encephalitis
Guillain-Barré syndrome
Hemorrhagic stroke (intracerebral)
Ischemic stroke
Lumbar radiculopathy
Malignant spinal cord compression
Migraine
Peripheral neuropathy (acute)
Retropharyngeal abscess
Schizophrenia (acute exacerbation)
Seizure (breakthrough:known epilepsy)
Seizure (first-time)
Spinal cord injury
Status epilepticus
Subarachnoid hemorrhage
Tension headache
Transient ischemic attack
Traumatic brain injury (moderate-severe)
Vestibular neuritis
Viral meningitis
Gastrointestinal Presentations
Acute appendicitis
Acute cholecystitis
Acute diverticulitis
Acute pancreatitis
Anal fissure
Choledocholithiasis and cholangitis
Clostridioides difficile colitis
Gastritis
Gastroenteritis (viral and bacterial)
Gastroesophageal reflux disease
Incarcerated or strangulated hernia
Inflammatory bowel disease flare
Large bowel obstruction
Lower GI hemorrhage
Peptic ulcer disease
Perforated viscus
Small bowel obstruction
Upper GI hemorrhage
Genitourinary and Reproductive Presentations
Acute prostatitis
Acute urinary retention
Ectopic pregnancy
Epididymitis
Orchitis
Ovarian torsion
Paraphimosis
Pelvic inflammatory disease
Priapism
Pyelonephritis
Renal laceration
Ruptured ovarian cyst
Testicular torsion
Tubo-ovarian abscess
Urinary tract infection (uncomplicated)
Urolithiasis (renal colic)
Vaginal bleeding (non-pregnant)
Infectious Disease Presentations
Acute sinusitis
Acute tonsillitis
Acute upper respiratory infection
Animal bite
Bacterial meningitis
Cellulitis
Conjunctivitis (bacterial)
Dental abscess
Endocarditis
Febrile neutropenia
Fournier gangrene
Hand-foot-mouth disease
Hepatitis (acute)
Herpes zoster
HIV-related illness
Human bite
Impetigo
Infected diabetic foot ulcer
Infectious mononucleosis
Influenza
Necrotizing fasciitis
Osteomyelitis
Otitis externa
Parasitic infection
Periorbital cellulitis
Peritonsillar abscess
Scabies
Sepsis
Septic arthritis
Spontaneous bacterial peritonitis
Tick-borne illness (Lyme disease)
Tinea infection
Tuberculosis
Viral exanthem
Wound infection
Trauma Presentations
Achilles tendon rupture
ACL and mceniscus tear
Ankle fracture
Ankle sprain
Burn
Calcaneus fracture
Cervical spine fracture
Clavicle fracture
Dental avulsion
Distal radius fracture
Drowning
Elbow fracture and dislocation
Electrical injury
Facial bone fracture
Facial laceration
Femur fracture
Fingertip amputation
Forearm fracture (radius and ulna)
Frostbite
Hand:finger laceration
Heat exhaustion
Heat stroke
Hip fracture
Humeral shaft fracture
Knee dislocation
Knee sprain
Lightning injury
Mandible fracture
Metacarpal fracture
Metatarsal fracture
Muscle strain
Nasal fracture
Non-accidental trauma
Orbital fracture
Patella fracture
Phalanx fracture (finger)
Proximal humerus fracture
Pulmonary contusion
Rib fracture
Rotator cuff tear (acute traumatic)
Scalp laceration
Scaphoid fracture
Shoulder dislocation
Skull fracture
Splenic laceration
Sternal fracture
Supracondylar pediatric fracture
Tendon laceration (hand:wrist)
Thoracic and lumbar spine fracture
Tibia:fibula fracture
Tibial plateau fracture
Toe fracture
Traumatic epistaxis
Traumatic hyphema
Toxicologic Presentations
Acetaminophen toxicity
Alcohol intoxication
Alcohol withdrawal
Anticholinergic toxicity
Anticoagulant overdose
Benzodiazepine overdose
Benzodiazepine:sedative overdose
Beta-blocker and calcium channel blocker toxicity
Carbon monoxide poisoning
Caustic ingestion
Digoxin toxicity
Drug eruption
Foreign body ingestion
Opioid intoxication
Opioid overdose
Opioid withdrawal
Organophosphate
Salicylate toxicity
Serotonin syndrome
Stimulant intoxication (cocaine, methamphetamine)
Tricyclic antidepressant overdose
Psychiatric Presentations
Acute anxiety
Acute psychosis
Agitation:behavioral emergency
Bipolar disorder
Conversion disorder
Major depressive episode
Neuroleptic malignant syndrome
Suicidal ideation and attempt
Musculoskeletal and Rheumatologic Presentations
Acute low back pain (mechanical)
Bursitis
Cervical radiculopathy
Costochondritis
Gout (acute)
Lumbar radiculopathy
Pseudogout
Tendinitis
Dermatology Presentations
Acute eczema (Eczema acute flare)
Allergic contact dermatitis
Erythema multiforme
Henoch-Schönlein purpura
Pressure injury
Psoriasis (acute flare)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria (acute)
Environmental and Exposure Presentations
Envenomation (snake, spider, insect)
High-altitude illness
Hypothermia
Hematologic and Oncologic Presentations
Acute chest syndrome
Coagulopathy
Hyperviscosity syndrome
Sickle cell crisis (vaso-occlusive)
Symptomatic anemia
Thrombocytopenia (severe)
Tumor lysis syndrome
Pediatric-Specific Presentations
Bronchiolitis
Croup
Emergency delivery
Febrile seizure
Kawasaki disease
Neonatal jaundice
Neonatal sepsis
Nursemaid's elbow
Pediatric fever 0 to 28 days
Pediatric fever 29 to 60 days
Pediatric fever 61 to 90 days
Pyloric stenosis
Slipped capital femoral epiphysis
Intussusception
Endocrine and Metabolic Presentations
Adrenal crisis
Diabetic ketoacidosis
Hypercalcemia
Hyperosmolar hyperglycemic state
Hypertensive emergency
Hypertensive urgency
Hypoglycemia
Myasthenia gravis crisis
Myxedema coma
Severe hyperkalemia
Severe hyponatremia
Thyroid storm
ENT and Maxillofacial Presentations
Acute laryngitis
Acute otitis media
Acute pharyngitis
Cerumen impaction
Epistaxis (anterior)
Nasal foreign body
Otitis externa
Tympanic membrane perforation
Ophthalmologic Presentations
Acute angle-closure glaucoma
Central retinal artery occlusion
Chemical eye injury
Corneal abrasion
Corneal ulcer
Globe rupture
Ocular foreign body
Orbital cellulitis
Retinal detachment
Obstetric Presentations
Hyperemesis gravidarum
Painful vaginal bleeding in pregnancy
Placenta previa
Placental abruption
Preeclampsia:eclampsia
Preterm labor
Threatened:inevitable:incomplete abortion
Systemic and Miscellaneous Presentations
Anaphylaxis
Angioedema
Cannabis-induced hyperemesis
Candidemia
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Procedures
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ECG Guide
Back
Clinical Assessment Checklist
Browse categories and answer follow-up questions to refine your symptom profile.
Approach to the Critical Patient
Immediate stabilization
Septic shock recognition
▶
MAP < 65 mmHg despite adequate fluid resuscitation
Vasopressor requirement to maintain MAP
Lactate >= 2 mmol/l
Initiate norepinephrine 0.01–0.5 mcg/kg/min IV, titrate to MAP >= 65 mmHg
Antifungal urgency
▶
Echinocandin within 1 hour for septic shock with candidemia risk factors
Delay > 24 hours associated with near-100% mortality in septic shock
Do not wait for culture confirmation before initiating therapy in the critically ill
Airway and oxygenation
▶
SpO2 target >= 92%
Supplemental oxygen titration
Intubation if respiratory failure secondary to metastatic pneumonia or sepsis
Monitoring and escalation
Escalation triggers
▶
Persistent fever > 72 hours on appropriate antifungal therapy
▶
Reassess for source, repeat cultures, imaging for deep-seated foci
Positive blood cultures > 5 days on therapy
▶
Suggests uncontrolled source, endovascular infection, or deep-seated candidiasis
New visual symptoms
▶
Emergent ophthalmology consult for endophthalmitis
New cardiac murmur or embolic phenomena
▶
Urgent echocardiography, cardiology consult
Monitoring bundle
▶
Blood cultures every 24–48 hours until documented clearance
Repeat electrolytes, creatinine, LFTs every 48 hours on antifungals
QTc monitoring if transitioning to azoles
Key consults
Consultation triggers
▶
Infectious diseases — associated with improved survival (HR 0.81), IDSA Class I
Ophthalmology — dilated fundoscopic exam within first week for all non-neutropenic patients
Cardiology or cardiac surgery — if endocarditis confirmed or strongly suspected
Interventional radiology or surgery — for drainage of abscesses or source control
History
Presenting symptoms
Fever phenotype
▶
Fever unresponsive to broad-spectrum antibiotics — most common presentation
Rigors, chills
Hemodynamic instability disproportionate to apparent bacterial source
Ophthalmologic symptoms
▶
Blurred vision
Floaters
Eye pain or photophobia
Screen all patients — endophthalmitis complicates 1.8–10% of candidemia cases
Metastatic symptoms
▶
Back or vertebral pain (osteomyelitis)
Joint pain or swelling (septic arthritis)
Abdominal pain (intra-abdominal abscess, hepatosplenic candidiasis)
Flank pain or dysuria (renal abscess)
New cardiac murmur or pleuritic chest pain (endocarditis)
Headache or altered mental status (CNS involvement)
Risk factors
Healthcare exposure risk factors
▶
Central venous catheter — present in 64–73% of candidemia cases
ICU admission — 50–67% of candidemia cases occur in ICU
Prior or current broad-spectrum antibiotic exposure — present in 77–81% of cases
Total parenteral nutrition (TPN)
Recent surgery, especially abdominal, GI, or thoracic
Renal replacement therapy or acute kidney injury
Prior antifungal therapy (raises resistance concern)
Patient-level risk factors
▶
Malignancy — hematologic or solid organ (~37–39% of candidemia cases)
Neutropenia (ANC < 0.5 x10^9/L)
Solid organ or hematopoietic cell transplant recipient
Diabetes mellitus
Chronic liver disease or cirrhosis
Injection drug use — accounts for ~10% of cases
HIV/AIDS or other primary immunodeficiency
Burns or major trauma
COVID-19-associated critical illness (elevated incidence 2020–2021)
Candida colonization history
▶
Prior Candida isolation at any site
Multifocal colonization (>2 body sites) — used in Candida Score
Prior episode of invasive candidiasis
Timeline and exposure context
Onset timeline
▶
Median time from admission to candidemia diagnosis is 5 days (IQR 0–16)
Duration of current hospitalization
Duration of CVC placement
Prior medical history
▶
Abdominal surgery history, anastomotic leak, peritonitis
Prior antifungal exposure — echinocandin resistance risk in C. glabrata
Recent chemotherapy or immunosuppressive drugs
Corticosteroid use
Physical Exam
Vital signs
Hemodynamic status
▶
Temperature — fever may be absent in immunosuppressed or neutropenic patients
Heart rate — tachycardia
Blood pressure — hypotension as septic shock marker
Respiratory rate — tachypnea from sepsis or pulmonary metastatic involvement
SpO2
MAP < 65 mmHg — ICU-level care trigger
Targeted organ exam
Ophthalmologic exam
▶
Dilated fundoscopic examination
▶
Fluffy white chorioretinal lesions — pathognomonic for ocular candidiasis
Vitreal extension — endophthalmitis pattern
Sensitivity for detection higher when performed > 7 days from first positive culture
Cardiovascular exam
▶
Auscultation for new or changing murmur
▶
Endocarditis found in ~11% of candidemia patients undergoing echocardiography
Peripheral stigmata of endocarditis (Osler nodes, Janeway lesions, splinter hemorrhages)
Skin exam
▶
Erythematous papular or nodular lesions on trunk and extremities
▶
Disseminated cutaneous candidiasis pattern
CVC insertion site — erythema, warmth, purulence, tenderness
Abdominal exam
▶
Tenderness — hepatosplenic or intra-abdominal candidiasis
Peritoneal signs — perforation or abscess
Hepatosplenomegaly
Musculoskeletal exam
▶
Vertebral point tenderness (osteomyelitis)
Joint effusion or warmth (septic arthritis)
Neurologic exam
▶
Altered mental status — CNS candidiasis (rare, < 1%)
Focal neurologic deficits
Oropharynx
▶
Oral thrush — indicator of mucosal colonization
Presence does not confirm invasive disease
Differential Diagnosis
Life-threatening mimics
Bacterial bloodstream infection / sepsis
▶
Most common mimic — coexists with candidemia in ~20% of cases
ICD-10: A41.9 (Sepsis, unspecified organism)
Blood cultures with gram stain and sensitivities required to differentiate
Infective endocarditis (bacterial)
▶
ICD-10: I33.0
Consider if persistent bacteremia, new murmur, embolic events
Aspergillosis or mucormycosis
▶
ICD-10: B44.1, B46.5
Neutropenic and transplant patients at highest risk
Galactomannan and CT chest distinguish aspergillosis
Healthcare-associated infections
Catheter-related bloodstream infection (non-Candida)
▶
ICD-10: T82.7XXA
Similar risk factors — CVC, ICU, broad-spectrum antibiotics
Intra-abdominal abscess (bacterial)
▶
ICD-10: K65.1
Especially post-surgical — CT-guided drainage and cultures required
Clostridioides difficile infection
▶
ICD-10: A04.71
Antibiotic-associated, fever and leukocytosis without clear source
Other considerations
Drug fever
▶
Diagnosis of exclusion — temporal relationship with new medication
Rash, eosinophilia may be present
Candida auris bloodstream infection
▶
ICD-10: B37.7 (Candida septicemia)
Multidrug-resistant emerging species — 0.4% of U.S. candidemia cases but increasing
Nationally notifiable in the U.S.
Viral sepsis syndrome
▶
Influenza, CMV, EBV reactivation in immunosuppressed hosts
Viral PCR panel to differentiate
Laboratory Tests
Blood cultures
Blood culture collection
▶
Gold standard for candidemia diagnosis
Minimum 2–3 sets (40–60 mL total blood volume) from separate venipunctures
Sensitivity 60–90%; specificity near 100%
Time to positivity typically 1–7 days — slower for Candida than bacteria
Repeat cultures every 24–48 hours until documented clearance (IDSA Class I)
Molecular and biomarker testing
Beta-D-glucan (BDG)
▶
Sensitivity 50–90%, specificity 70–100%
High negative predictive value — useful for ruling out in low-risk patients
False positives with IVIG, albumin, beta-lactams, hemodialysis membranes, gauze
Adjunct only — not diagnostic alone (IDSA Level B evidence)
T2Candida panel
▶
Sensitivity ~90%, specificity > 95%
Turnaround 4–5 hours — significantly faster than culture
Detects C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei
Does not replace blood cultures for susceptibility testing
Candida PCR
▶
Sensitivity 90–95%, specificity > 90%
Limited standardization across laboratories
May detect candidemia when cultures are negative
Antifungal susceptibility
Susceptibility testing
▶
Strongly recommended for all Candida bloodstream isolates (IDSA Class I)
MALDI-TOF mass spectrometry for rapid species identification from positive cultures
Echinocandin resistance most common in C. glabrata (Nakaseomyces glabrata)
Fluconazole resistance: C. krusei (intrinsically resistant), C. glabrata (emerging)
C. auris — often multidrug-resistant; pan-resistant isolates reported
Organ function and severity labs
Complete blood count
▶
Thrombocytopenia — independent mortality risk factor in candidemia
Leukocytosis or leukopenia — severity marker
Neutrophil-to-lymphocyte ratio — associated with ICU mortality
Comprehensive metabolic panel
▶
Creatinine and eGFR — baseline before nephrotoxic antifungals
Acute kidney injury — independent mortality predictor
LFTs — hepatic candidiasis, drug hepatotoxicity monitoring
Albumin — hypoalbuminemia is independent mortality predictor
Lactate
▶
>= 2 mmol/l — sepsis with organ hypoperfusion
>= 4 mmol/l — septic shock, highest mortality stratum
Procalcitonin and CRP
▶
Nonspecific for fungal infection
May be used to track treatment response over time
Do not use to rule out candidemia
Diagnostic Tests
Scoring Systems
Candida Score (ICU risk stratification)
▶
Components: surgery (+1), TPN (+1), multifocal Candida colonization (+1), severe sepsis (+2)
Score >= 3 identifies ICU patients at high risk for invasive candidiasis
Sensitivity ~78%, specificity ~66% for invasive candidiasis in ICU
Used to guide empiric antifungal initiation decisions
EQUAL Candida Score (guideline adherence)
▶
Measures adherence to ECMM/ISHAM guideline recommendations
Each point decrease in adherence score associated with 8–9% increased mortality
Domains: antifungal selection, ophthalmologic exam, echocardiography, CVC removal, follow-up cultures
APACHE II score
▶
Increasing APACHE II — independent predictor of candidemia mortality
Used for ICU risk stratification and mortality estimation
Pitt Bacteremia Score
▶
Adapted for candidemia prognostication in non-ICU patients
Score >= 4 associated with significantly increased mortality
MRI
MRI indications in candidemia
▶
MRI brain — suspected CNS candidiasis (altered mental status, focal deficits)
▶
Microabscesses appear as small enhancing lesions on T1 post-gadolinium
Meningeal enhancement in Candida meningitis
MRI spine — vertebral osteomyelitis or epidural abscess
▶
T2 hyperintensity in involved disc and vertebral bodies
Post-gadolinium T1 for extent of epidural involvement
MRI liver and spleen — hepatosplenic candidiasis (chronic disseminated)
▶
Bull's-eye or target lesions on T2-weighted sequences
Typically occurs during neutrophil recovery phase
MRI superior to CT for soft tissue and CNS involvement characterization
CT
CT indications in candidemia
▶
CT abdomen and pelvis — suspected intra-abdominal candidiasis, hepatosplenic abscesses, renal abscesses
▶
Target or wheel-within-wheel lesions in liver and spleen on contrast CT
Renal abscesses — hypodense, peripherally enhancing lesions
CT chest — pulmonary candidiasis (uncommon but seen in severely immunocompromised)
▶
Non-specific — nodules, consolidation, ground-glass opacities
CT spine — vertebral osteomyelitis when MRI unavailable or contraindicated
CT-guided drainage — therapeutic role for amenable abscesses
Not routinely required for uncomplicated candidemia that clears promptly
Ultrasound
Echocardiography
▶
Transthoracic echocardiography (TTE) — initial screen for all candidemia patients
▶
Endocarditis found in ~11% of patients undergoing echocardiography
Vegetation, valve destruction, perivalvular abscess
Transesophageal echocardiography (TEE) — if TTE non-diagnostic and high clinical suspicion
▶
Superior sensitivity for prosthetic valve endocarditis and perivalvular extension
Indicated if persistent candidemia, S. aureus co-infection, prosthetic valve, IVDU
Abdominal ultrasound
▶
Hepatosplenic candidiasis — multiple hypoechoic target lesions in liver and spleen
Renal abscesses — hypoechoic, complex lesions
Useful for bedside assessment in unstable patients
Lower sensitivity than CT for small deep-seated lesions
Disposition
Admission criteria
All candidemia patients require hospital admission
▶
IV antifungal therapy mandatory — no outpatient oral-only regimen for candidemia
Source control requiring procedural or surgical intervention
Monitoring for metastatic complications
ICU admission indications
▶
Septic shock (vasopressor requirement, MAP < 65 mmHg)
Multiorgan dysfunction
Respiratory failure
Rapidly worsening clinical status
Consultation and specialist involvement
Infectious diseases consultation
▶
Associated with improved survival (HR 0.81) — strongly recommended for all cases
Guides antifungal selection, duration, and step-down decisions
Ophthalmology consultation
▶
Dilated fundoscopic exam within first week for all non-neutropenic patients (IDSA Class I)
Repeat exam if initial exam performed < 7 days from first positive culture
Cardiology or cardiac surgery — confirmed or suspected endocarditis
Neurosurgery — CNS involvement with abscess amenable to drainage
Interventional radiology — percutaneous drainage of accessible abscesses
Step-down and discharge planning
Copy
Criteria for step-down from IV echinocandin to oral fluconazole
▶
Hemodynamically stable
Blood cultures documented negative
Fluconazole-susceptible isolate confirmed
Source controlled (CVC removed, abscess drained)
Non-neutropenic
Tolerating oral medications
Transition at day 5–7 of therapy (IDSA Class I recommendation)
Discharge criteria
▶
Clinically stable on oral azole step-down
Documented blood culture clearance
Reliable outpatient follow-up arranged within 1–2 weeks
Home ophthalmology follow-up if initial exam was early or normal
Treatment
Antifungal therapy — first-line
Echinocandins (first-line for all candidemia, IDSA/ECMM/ISHAM Class I)
▶
Caspofungin IV
▶
Loading dose: 70 mg IV once
Maintenance: 50 mg IV daily
Hepatic adjustment: reduce maintenance to 35 mg daily for Child-Pugh B/C
Micafungin IV
▶
100 mg IV daily (no loading dose required)
Dose 150 mg IV daily for neutropenic patients or suspected less-susceptible species
Anidulafungin IV
▶
Loading dose: 200 mg IV once
Maintenance: 100 mg IV daily
Rezafungin IV (strongly recommended, 2025 ECMM guideline)
▶
Loading dose: 400 mg IV on day 1
Maintenance: 200 mg IV weekly
Advantage: once-weekly dosing
Treatment duration: 14 days from first negative blood culture (IDSA Class I)
Antifungal therapy — alternatives
Fluconazole IV or oral
▶
Loading dose: 800 mg (12 mg/kg) IV or PO once
Maintenance: 400 mg (6 mg/kg) daily
Reserved for: non-critically ill, hemodynamically stable, fluconazole-susceptible isolate, no prior azole exposure
Not for empiric use in ICU or critically ill patients
Step-down from echinocandin at day 5–7 if all criteria met
Liposomal amphotericin B
▶
3–5 mg/kg IV daily
For azole- and echinocandin-resistant strains
Monitor renal function — less nephrotoxic than conventional amphotericin B deoxycholate
Conventional amphotericin B deoxycholate not recommended due to nephrotoxicity (IDSA Class III)
Voriconazole
▶
Loading: 6 mg/kg IV every 12 hours x 2 doses
Maintenance: 4 mg/kg IV every 12 hours; transition to 200 mg PO every 12 hours
Preferred for step-down when mold coverage also needed
Drug of choice for ocular candidiasis — better intraocular penetration than echinocandins
Source control
Central venous catheter (CVC) removal
▶
Remove all CVCs as soon as feasible — IDSA Class I, strongly recommended
CVC retention associated with longer candidemia duration and higher mortality
If CVC cannot be removed (hemodialysis catheter, no other access), antifungal lock therapy may be considered as adjunct
Surgical and interventional source control
▶
Drainage of intra-abdominal abscesses
Management of anastomotic leaks
Removal of infected prosthetic material when feasible
Metastatic complication management
Endophthalmitis management
▶
Switch from echinocandin to fluconazole 400–800 mg daily or voriconazole
Echinocandins have inadequate intraocular penetration
Duration: minimum 4–6 weeks for chorioretinitis without vitreal involvement
Intravitreal amphotericin B 5–10 mcg in 0.1 mL or voriconazole 25–100 mcg in 0.1 mL
Vitrectomy if vitreal opacity or retinal detachment threat
Endocarditis management
▶
Liposomal amphotericin B 3–5 mg/kg daily or echinocandin as initial therapy
Cardiac valve surgery strongly recommended — medical management alone has high failure rate
Duration: minimum 6 weeks after valve replacement, longer for native valve
Fluconazole suppressive therapy after completion for select patients at high relapse risk
CNS candidiasis
▶
Liposomal amphotericin B 5 mg/kg daily + flucytosine 25 mg/kg PO four times daily
Step-down to fluconazole 400–800 mg daily once stable
Duration: minimum 4 weeks after last positive CSF culture and symptom resolution
Vertebral osteomyelitis / septic arthritis
▶
Fluconazole 400 mg daily after initial echinocandin therapy
Duration: minimum 6–12 months
Surgical debridement if spinal instability or neurologic compromise
Hemodynamic and supportive care
Sepsis resuscitation
▶
Crystalloid resuscitation 30 mL/kg IV for hypoperfusion within first 3 hours
Norepinephrine 0.01–0.5 mcg/kg/min — first-line vasopressor for septic shock
Vasopressin 0.03 units/min additive for refractory shock
Hydrocortisone 200 mg/day IV for vasopressor-refractory shock
Nutrition optimization
▶
Transition from TPN to enteral nutrition when feasible — reduces candidemia risk
Adequate protein and caloric support for immune recovery
Special Populations
Pregnancy
Epidemiology in pregnancy
▶
Candidemia uncommon in uncomplicated pregnancy — most cases in ICU or post-surgical settings
Candidemia in pregnancy associated with preterm delivery, fetal loss, and neonatal candidiasis
Mucosal candidiasis (vulvovaginal) extremely common; does not require systemic therapy
Antifungal safety
▶
Fluconazole — contraindicated in first trimester (teratogenic, associated with cardiac septal defects and craniosynostosis at doses >= 150 mg)
Fluconazole single-dose 150 mg in first trimester has uncertain risk — avoid if possible
Echinocandins — limited human data; animal data show fetal harm at high doses; used when benefit outweighs risk in severe invasive candidemia
Liposomal amphotericin B — preferred agent in pregnancy for invasive candidiasis
▶
3–5 mg/kg IV daily
Monitor for maternal nephrotoxicity and electrolyte disturbances
Azoles (voriconazole, posaconazole, itraconazole) — contraindicated in pregnancy
Monitoring
▶
Fetal monitoring throughout treatment
Maternal renal function with amphotericin B
Obstetric and maternal-fetal medicine consultation
Geriatric
Epidemiology and risk
▶
Incidence increases with age — peak incidence in patients > 65 years
Higher crude in-hospital mortality (approaching 50% in > 75 years)
Greater prevalence of comorbidities: diabetes, CKD, malignancy, CHF
Clinical presentation differences
▶
Fever may be blunted or absent
Altered mental status as predominant presenting feature
Higher likelihood of atypical or nonspecific presentation
Pharmacologic considerations
▶
Echinocandins — no dose adjustment required for age alone; preferred first-line
Fluconazole — renal dose adjustment if eGFR < 50 mL/min/1.73m2
▶
Reduce dose by 50% for severe renal impairment
Amphotericin B — nephrotoxicity risk amplified in elderly with baseline CKD
Monitor for drug interactions — polypharmacy common; azoles inhibit CYP3A4 and CYP2C9
QTc prolongation risk with azoles in patients on other QT-prolonging medications
Source control
▶
CVC removal may require careful assessment of access alternatives
Higher surgical risk — multidisciplinary risk-benefit assessment for valve surgery
Pediatrics
Epidemiology
▶
Neonates (especially premature < 29 weeks) at highest risk — incidence 1–10 per 1000 NICU admissions
C. parapsilosis dominant species in neonates and children (catheter-associated)
Pediatric candidemia incidence declining due to antifungal prophylaxis in NICU settings
Children with hematologic malignancy or HCT also at high risk
Neonatal candidemia
▶
Amphotericin B deoxycholate 1 mg/kg/day IV — first-line for neonates (CNS penetration superior)
Liposomal amphotericin B 3–5 mg/kg/day IV — alternative, lower nephrotoxicity
Fluconazole 12 mg/kg/day IV or PO (max 800 mg/day) — step-down or prophylaxis
Echinocandins in neonates: use only when above agents failed or resistant — limited PK data
Micafungin 4–10 mg/kg/day in neonates — limited but emerging evidence
Pediatric (non-neonatal) candidemia
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Caspofungin 70 mg/m2 loading dose (max 70 mg), then 50 mg/m2 daily (max 50 mg)
Micafungin 2–4 mg/kg/day (max 100 mg)
Anidulafungin 1.5 mg/kg/day (max 100 mg)
Fluconazole 6–12 mg/kg/day (max 400–800 mg) — for step-down
Duration: 14 days from first negative blood culture (same as adults)
Prophylaxis
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Fluconazole prophylaxis 3–6 mg/kg/day reduces candidemia in ELBW neonates
Recommended in NICU units with incidence > 2 per 100 NICU admissions
Per NIH/OAR pediatric OI guidelines (2025)
Ophthalmologic screening
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Dilated exam indicated in pediatric candidemia — endophthalmitis can cause permanent vision loss
Neonatal fundoscopy within first week of treatment
Background
Epidemiology
Incidence and burden
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Most common healthcare-associated invasive fungal infection in the U.S. and Europe
U.S. incidence: approximately 7–9 per 100,000 population
Crude in-hospital mortality: 25–46%
Attributable mortality: 10–20%
Estimated 46,000 cases annually in the U.S. (pre-COVID era data)
Species distribution (U.S. data 2017–2021)
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C. albicans: 37% (most common, generally fluconazole-susceptible)
C. glabrata (Nakaseomyces glabrata): 30% — higher rates of fluconazole and echinocandin resistance
C. parapsilosis: 14% — catheter-associated, echinocandin resistance emerging
C. tropicalis: less common, associated with hematologic malignancy
C. krusei (Pichia kudriavzevii): intrinsically fluconazole-resistant
C. auris: 0.4% but rapidly increasing — often multidrug-resistant, nationally notifiable
Population distribution
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50–67% of cases occur in ICU patients
~37–39% in patients with malignancy
~10% in persons who inject drugs (PWID) — increasing proportion
Sex distribution: slightly male predominant
Peak incidence: elderly (> 65 years) and neonates
Temporal trends
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COVID-19 pandemic associated with increased candidemia incidence (2020–2021)
C. auris rapid emergence since 2016 — now endemic in multiple U.S. states
Echinocandin resistance rising, especially in C. glabrata
Pathophysiology
Routes of infection
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Translocation from GI tract — most common route in ICU patients
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Mucosal disruption from surgery, chemotherapy, or critical illness
Altered microbiome from broad-spectrum antibiotics permits Candida overgrowth
Catheter-related infection
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Biofilm formation on catheter surfaces — Candida forms robust biofilms
Luminal (hub contamination) or extraluminal (skin flora) routes
Hematogenous seeding from primary mucosal or skin focus
Virulence mechanisms
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Biofilm formation — dramatically reduces antifungal susceptibility (up to 1000-fold)
Phenotypic switching between yeast and hyphal forms
Secretion of hydrolases (phospholipases, proteinases) — tissue invasion
Immune evasion via mannan and beta-glucan cell wall masking
Metastatic seeding pattern
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Hematogenous dissemination to: eyes, heart valves, kidney, liver, spleen, bone, CNS
Biofilm on damaged endothelium or prosthetic material
Endophthalmitis via choroidal circulation — fundus lesions represent microabscesses
Hepatosplenic candidiasis — occurs during neutrophil recovery, immune reconstitution
Host defense failure
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Neutropenia — impairs killing of yeast and hyphae
Defective monocyte/macrophage function — corticosteroids, transplant immunosuppression
Disrupted mucosal barrier — surgery, chemotherapy, CVC
Therapeutic Considerations
Antifungal pharmacology
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Echinocandins — inhibit (1,3)-beta-D-glucan synthase; fungicidal against Candida
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Minimal drug interactions — not CYP metabolized significantly
Poor CNS and vitreous penetration — avoid if CNS or ocular candidiasis
Hepatic metabolism — dose adjust in severe hepatic impairment (caspofungin)
Azoles — inhibit ergosterol synthesis (CYP51/Erg11); fungistatic against Candida
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Major CYP3A4 interactions — warfarin, calcineurin inhibitors, statins
QTc prolongation risk — baseline and monitoring ECG
Good CNS and vitreous penetration — preferred for CNS and ocular candidiasis
Amphotericin B — binds ergosterol, membrane disruption; fungicidal
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Nephrotoxicity — monitor creatinine, K+, Mg2+ closely
Infusion reactions — premedication with acetaminophen, diphenhydramine
Resistance considerations
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Echinocandin resistance — FKS gene mutations (FKS1, FKS2); especially C. glabrata
Fluconazole resistance — ERG11 mutations, efflux pump upregulation
C. auris — frequently resistant to fluconazole, amphotericin B; echinocandin-resistant strains reported
Susceptibility testing guides therapy — MIC breakpoints per CLSI or EUCAST standards
Guideline adherence and outcomes
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ECMM Candida III study: each point decrease in EQUAL Candida Score associated with 8–9% increased 30-day mortality
Key adherence domains: ID consultation, echinocandin first-line, CVC removal, ophthalmologic exam, echocardiography, follow-up blood cultures
Prophylaxis — fluconazole or micafungin prophylaxis recommended in high-risk surgical or NICU populations per IDSA guidelines
Patient Discharge Instructions
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Discharge education for Candidemia
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You have been diagnosed with candidemia — a serious yeast (fungal) infection in your bloodstream
You will need to continue antifungal medication by mouth (usually fluconazole) as prescribed
Do not skip any doses — incomplete treatment can lead to relapse
Take the full prescribed course even if you feel better
Follow-up instructions
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See your doctor or infectious disease specialist within 1–2 weeks of discharge
A repeat eye examination may be recommended if your initial eye exam was performed early in your illness
Your doctor will order repeat blood tests and may check for recurrence
Return to emergency department immediately if
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Fever above 38.0°C (100.4°F) returns or does not resolve
Rigors or shaking chills
New or worsening blurred vision, floaters, or eye pain
Chest pain, new heart pounding, or palpitations
Back pain, joint pain, or joint swelling
Abdominal pain, nausea, or vomiting
Confusion, new weakness, or difficulty speaking
Skin rash or new lesions
Any rapid deterioration in how you feel
Lifestyle and prevention
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Intravenous lines increase infection risk — report any redness, swelling, or discharge at IV sites immediately
Good hand hygiene reduces transmission risk — wash hands frequently
Avoid unnecessary antibiotics — overuse contributes to fungal overgrowth
If you use IV drugs, seek addiction medicine support — injection drug use is a major risk factor for candidemia recurrence
Maintain blood sugar control if diabetic — hyperglycemia increases infection risk
References
Guidelines and key sources
IDSA Clinical Practice Guideline for Candidiasis 2016
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Pappas PG, Kauffman CA, Andes DR, et al.
Clinical Infectious Diseases 2016
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725385/
ECMM/ISHAM/ASM Global Guideline for Candidiasis 2025
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Cornely OA, Sprute R, Bassetti M, et al.
The Lancet Infectious Diseases 2025
https://pubmed.ncbi.nlm.nih.gov/39956121
ECMM Candida III Multinational Observational Cohort Study
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Hoenigl M, Salmanton-Garcia J, Egger M, et al.
The Lancet Infectious Diseases 2023
https://pubmed.ncbi.nlm.nih.gov/37254300
Epidemiologic surveillance
U.S. Population-Based Active Surveillance 2017–2021
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Jenkins EN, Gold JAW, Benedict K, et al.
MMWR Surveillance Summaries 2025
https://pubmed.ncbi.nlm.nih.gov/40424200
U.S. Population-Based Active Surveillance 2012–2016
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Toda M, Williams SR, Berkow EL, et al.
MMWR Surveillance Summaries 2019
https://pubmed.ncbi.nlm.nih.gov/31557145
Landmark reviews and trials
Invasive Candidiasis — NEJM Review
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Kullberg BJ, Arendrup MC.
New England Journal of Medicine 2015
https://www.nejm.org/doi/full/10.1056/NEJMra1315399
Risk Factors for Candidemia — Prospective Matched Case-Control
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Poissy J, Damonti L, Bignon A, et al.
Critical Care 2020
https://pubmed.ncbi.nlm.nih.gov/32188500
Candida and Invasive Mould Diseases in Non-Neutropenic Critically Ill Patients
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Colombo AL, de Almeida Junior JN, Slavin MA, et al.
The Lancet Infectious Diseases 2017
https://pubmed.ncbi.nlm.nih.gov/28774702
Ocular and cardiac complications
Prevalence of Ocular Candidiasis — Systematic Review and Meta-Analysis
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Phongkhun K, Pothikamjorn T, Srisurapanont K, et al.
Clinical Infectious Diseases 2023
https://pubmed.ncbi.nlm.nih.gov/36750934
AAO Recommendations on Screening for Endogenous Candida Endophthalmitis
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Breazzano MP, Bond JB, Bearelly S, et al.
Ophthalmology 2022
https://pubmed.ncbi.nlm.nih.gov/34293405
Do Patients With Candidemia Need an Ophthalmologic Examination?
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Lehman A, Tessier KM, Sattarova V, et al.
Open Forum Infectious Diseases 2024
https://pubmed.ncbi.nlm.nih.gov/39691288
Specialized populations
HCT Recipients — ASTCT Management Guidelines 2023
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Neofytos D, Steinbach WJ, Hanson K, et al.
Transplantation and Cellular Therapy 2023
https://linkinghub.elsevier.com/retrieve/pii/S2666-6367(23)00035-0
Pediatric OI Guidelines — NIH Office of AIDS Research 2025
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Kapogiannis BG, Yates F, Li W, et al.
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/pediatric-oi/guidelines-pediatric-oi.pdf
ATS Clinical Practice Guideline — Empiric Antifungal Therapy in Critical Care 2024
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Epelbaum O, Marinelli T, Haydour QS, et al.
American Journal of Respiratory and Critical Care Medicine 2024
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755356/
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.
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Candidemia