Candida infection and candidemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Mucosal candidiasis arises when local flora overgrow after antibiotics, inhaled steroids, diabetes, pregnancy or immune dysfunction. Invasive candidiasis occurs when disrupted mucosa or skin, abdominal leakage, surgery or vascular devices permit yeast into sterile tissue or blood. Candida can form biofilm on catheters and prosthetic material, reducing antifungal activity and making physical source control essential.

Major invasive-disease risks include critical illness, prolonged broad-spectrum antibiotics, central venous access, total parenteral nutrition, recent gastrointestinal surgery or anastomotic leak, pancreatitis, renal replacement therapy, neutropenia, transplantation and repeated Candida colonisation. Clinical fever is non-specific and blood cultures miss some deep-seated disease, so pre-test probability, imaging, biomarkers and tissue sampling must be integrated.

Species identification changes management. C. glabrata complex can show azole resistance, C. krusei is intrinsically fluconazole resistant, C. parapsilosis can have higher echinocandin MICs, and C. auris is frequently fluconazole resistant with outbreak potential. Every invasive isolate warrants timely identification and susceptibility testing under microbiology or mycology oversight.

Key points

Candida commonly colonises the mouth, bowel, genital tract and skin; growth from sputum, a chronic wound or an asymptomatic urinary specimen usually does not prove invasive disease.
Candidemia is never dismissed as a contaminant. Take blood cultures before antifungal therapy when safe and immediately assess intravascular lines, abdomen, urinary instrumentation, heart, eyes and other metastatic sites.
First-line treatment for most critically ill adults with candidemia is an intravenous echinocandin, selected from anidulafungin, micafungin or caspofungin according to local formulary.
Anidulafungin has a usable adult regimen of 200 mg intravenously once, then 100 mg intravenously every 24 hours.
Step down to oral fluconazole only after clinical stability, documented bloodstream clearance, a susceptible species and a controlled source; fluconazole is not a safe automatic first dose for every patient.
Repeat blood cultures daily or on alternate days until clearance and treat uncomplicated candidemia for at least 14 days after the first negative culture and resolution of attributable symptoms.
Candida biomarkers such as serum 1,3-beta-D-glucan support but do not independently establish disease; tissue histology, culture and molecular testing are important in deep infection.
For C. auris, do not treat colonisation, use an echinocandin empirically for symptomatic infection, obtain susceptibility testing and apply contact precautions, isolation or cohorting and effective environmental disinfection.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Endogenous flora

Most Candida disease begins with the patient's own mucosal or skin flora entering tissue after barrier disruption, dysbiosis or immune failure.

Healthcare devices

Central catheters, urinary devices, parenteral nutrition and prosthetic material create access and biofilm surfaces that support persistent invasive infection.

Abdominal disruption

Gastrointestinal surgery, perforation, anastomotic leak, pancreatitis and repeated antibiotics permit bowel Candida to invade normally sterile abdominal spaces.

Candidozyma auris transmission

Unlike most Candida, C. auris readily colonises skin, survives on healthcare surfaces and spreads between patients through contact and equipment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Adhesion and invasion
Yeast adheres to epithelium or biomaterial, changes morphology in susceptible species and breaches damaged barriers into sterile tissue.
2
Biofilm persistence
Organisms embedded in catheter or prosthetic biofilm resist host clearance and antifungal exposure, sustaining bloodstream seeding until source control.
3
Haematogenous dissemination
Bloodstream yeast reaches retina, choroid, heart valves, kidney, liver, spleen, bone, joints and brain, producing anatomically protected foci.
4
Host inflammatory response
Innate recognition of fungal cell-wall components drives sepsis, while neutropenia or impaired cellular immunity reduces containment and alters lesion appearance.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Candidemia syndromeRed flag

Persistent fever, rigors or sepsis despite antibacterial therapy may be the only early presentation, particularly with a central line or abdominal source.

Abdominal candidiasisRed flag

Ongoing peritonitis, anastomotic leak, pancreatitis, abscess or recurrent postoperative sepsis can represent invasive Candida even when blood cultures remain negative.

Mucosal disease

Oropharyngeal candidiasis produces removable white plaques or erythematous soreness; odynophagia or retrosternal pain suggests oesophageal extension and deeper immune dysfunction.

Urinary isolation

Candiduria commonly reflects colonisation around a catheter; fever, obstruction, renal lesions, symptoms or planned urological instrumentation increase its significance.

Metastatic fociRed flag

Visual symptoms, focal bone or joint pain, skin nodules, new murmur or persistent organ dysfunction after bloodstream infection suggests disseminated seeding.

Candidozyma aurisRed flag

Illness resembles other invasive candidiasis, but persistent skin colonisation, healthcare transmission and multidrug resistance require immediate laboratory and IPC recognition.

Red flags requiring action

Shock, rising lactate, acute kidney injury, respiratory failure or altered consciousness with candidemia requires immediate critical-care and infection-specialist involvement.
Persistent positive blood cultures despite active therapy suggests an infected line, undrained focus, endocarditis, deep-organ disease or antifungal resistance.
Visual change, eye pain or photophobia during candidemia raises concern for ocular involvement and needs urgent ophthalmic assessment.
New murmur, embolic lesions, persistent bacteraemia or intracardiac material suggests Candida endocarditis and requires echocardiography plus surgical discussion.
Candidozyma auris identification or credible overseas-healthcare exposure requires immediate infection-prevention action even if the isolate represents colonisation rather than infection.
Neutropenia, pregnancy, CNS infection and hepatosplenic candidiasis materially alter diagnostic yield, drug choice, duration and specialist ownership.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line blood culturesFirst stepFirst line
Why
Recover Candida from blood, establish species and begin the clearance clock for treatment duration.
Interpretation and limitations
Take peripheral and line sets before antifungal therapy if this does not delay resuscitation. Any Candida from blood is clinically significant; repeat daily or every other day until negative.
02
Species identification and susceptibility
Why
Define predictable and acquired resistance and determine whether safe azole step-down is possible.
Interpretation and limitations
Use validated MALDI-TOF or molecular identification and request antifungal MICs for invasive isolates; unusual, resistant or C. auris isolates need specialist or reference-laboratory input.
03
Serum 1,3-beta-D-glucan
Why
Provide a non-culture marker that can support suspected invasive candidiasis when blood cultures are negative.
Interpretation and limitations
A positive result is not Candida-specific and false positives occur with dialysis filters, products and other fungi; a negative serial result may lower probability in a suitable population.
04
Deep-site sampling
Why
Diagnose abdominal, hepatic, splenic, bone, joint, CNS or other tissue disease and direct source control.
Interpretation and limitations
Send adequately sized sterile-site fluid or tissue for histology, microscopy, culture and molecular testing before antifungals where feasible; superficial swabs cannot substitute.
05
Source and dissemination imaging
Why
Locate an abscess, anastomotic leak, infected thrombus, hepatosplenic lesions or another protected focus.
Interpretation and limitations
Choose CT, ultrasound, MRI or echocardiography from symptoms and persistence. Negative early imaging does not exclude hepatosplenic disease during neutrophil recovery.
06
Ocular and cardiac assessment
Why
Detect endophthalmitis or endocarditis that changes drug penetration, duration and procedural management.
Interpretation and limitations
Urgently assess visual symptoms; apply local specialist policy for routine eye review. Obtain echocardiography for persistent candidemia, embolic signs, prosthetic valves or clinical suspicion.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bacterial bloodstream infection

Line infection, abdominal sepsis and endocarditis from bacteria present identically; paired cultures and source specimens should investigate both without therapeutic delay.

Invasive aspergillosis

Neutropenia, pulmonary nodules and fungal biomarkers overlap, but respiratory galactomannan, mould culture and tissue morphology support Aspergillus.

Mucosal colonisation

Candida growth from non-sterile sites without inflammation or organ dysfunction represents carriage rather than the cause of systemic illness.

Drug fever

Persistent fever during broad antimicrobial exposure may be drug related, but invasive infection and uncontrolled source must be excluded first.

Viral reactivation

CMV and other viral disease can produce fever and organ dysfunction in transplant recipients, requiring targeted molecular and tissue assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01CULTURE FIRSTRespond to suspected candidemiaFirst stepA high-risk patient has unexplained sepsis, persistent fever or yeast signalled in a blood-culture bottle.

1Take peripheral and catheter blood cultures, complete sepsis bloods and sample the most credible source before antifungal treatment if collection will not create harmful delay.
2Start an intravenous echinocandin promptly for unstable or high-risk disease, using an exact local formulary regimen and obtaining microbiology, infection and pharmacy input.
3Review every intravascular catheter, urinary device, abdominal drain and operative site; remove or exchange an implicated central line when feasible and drain collections urgently.
4Identify species and susceptibility, repeat cultures until clear, and search for ocular, cardiac or deep-organ spread when symptoms, persistence or host factors justify it.

02FIRST-LINEUse echinocandin inductionFirst lineCandidemia or invasive candidiasis is confirmed or strongly suspected in an adult without a site requiring superior CNS, eye or urinary penetration.

1Give anidulafungin 200 mg intravenously once then 100 mg every 24 hours, micafungin 100 mg intravenously every 24 hours, or caspofungin 70 mg once then 50 mg every 24 hours according to local policy.
2For caspofungin, follow the product and local protocol for patients above 80 kg and hepatic impairment; do not interchange echinocandin doses.
3Review response, blood-culture clearance and susceptibility each day rather than setting an unattended long course.
4Use liposomal amphotericin B or another specialist regimen when resistance, CNS or ocular disease, pregnancy, intolerance or breakthrough infection makes echinocandin therapy unsuitable.

03STEP-DOWNNarrow to an active oral azoleThe patient is stable, cultures have cleared, source control is adequate, oral absorption is reliable and the isolate is fluconazole susceptible.

1Use fluconazole 800 mg orally or intravenously as a loading dose, then 400 mg once daily for a susceptible uncomplicated isolate, adjusting for renal function.
2Do not step down C. auris routinely to fluconazole because resistance is common; follow actual susceptibility and mycology advice.
3Complete at least 14 days after the first documented negative blood culture and resolution of attributable symptoms in uncomplicated candidemia.
4Extend and redesign treatment for endocarditis, endophthalmitis, osteomyelitis, hepatosplenic or CNS disease according to site penetration, surgery and specialist guidance.

04COLONISATIONAvoid unnecessary systemic treatmentCandida is recovered from sputum, a non-sterile wound, catheter urine or another site without compatible invasive infection.

1Assess symptoms, host risk, device presence and specimen quality before labelling infection; Candida in respiratory secretions almost always represents colonisation.
2Remove or replace an unnecessary urinary catheter and correct obstruction; treat candiduria only for defined symptomatic or high-risk indications such as urological instrumentation.
3Treat local oral, vulvovaginal or skin disease with the narrowest site-appropriate agent while correcting diabetes, steroid technique or moisture where relevant.
4Do not expose an asymptomatic colonised patient to systemic antifungal treatment merely to sterilise a culture.

05C. AURIS IPCContain transmissible resistant yeastC. auris is suspected or identified from screening or clinical material.

1Alert microbiology and the IPC team immediately, verify identification and susceptibility, and report colonising and infecting episodes through the required UKHSA surveillance route.
2Place the patient in a single en-suite room where possible or cohort under IPC direction and use standard plus contact precautions for colonisation and infection alike.
3Use dedicated equipment and meticulous cleaning before disinfection with 1,000 ppm available chlorine or another proven effective product; avoid relying on quaternary ammonium compounds.
4Communicate status before transfer and on discharge, screen contacts according to IPC risk assessment and do not routinely attempt antifungal decolonisation.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

First-line echinocandin option for candidemia and invasive candidiasis in many acutely unwell adults.

Anidulafungin

Give 200 mg intravenously as a loading dose on day one, followed by 100 mg intravenously every 24 hours.

Review liver tests, infusion reactions and species susceptibility; penetration into urine, eye and CNS is limited, so those sites need a different specialist plan.

Alternative first-line echinocandin and empirical choice for adult C. auris infection pending susceptibility.

Micafungin

Give 100 mg intravenously every 24 hours for adult candidemia, with dose modification for specific deep sites only under specialist protocol.

Monitor liver function and interactions; echinocandin resistance can emerge during C. auris treatment, requiring repeat cultures and susceptibility when response falters.

Alternative echinocandin for candidemia or invasive candidiasis when locally selected.

Caspofungin

Give 70 mg intravenously once, then 50 mg intravenously every 24 hours; follow local product guidance for body weight above 80 kg and hepatic impairment.

Check hepatic function, interacting enzyme inducers and infusion reactions; use the exact caspofungin regimen rather than assuming class doses are interchangeable.

Oral step-down for stable patients after bloodstream clearance and susceptibility confirmation; also treats selected mucosal disease at lower regimens.

Fluconazole

For susceptible invasive disease, give 800 mg orally or intravenously once, then 400 mg once daily, with renal adjustment after the loading dose.

Review QT interval, liver injury, pregnancy and CYP interactions; avoid for intrinsically resistant C. krusei, many C. auris isolates and unconfirmed C. glabrata susceptibility.

Alternative for echinocandin resistance, treatment failure, pregnancy or sites such as CNS and eye where a tailored regimen is required.

Liposomal amphotericin B

Use 3 to 5 mg/kg intravenously every 24 hours for resistant or anatomically complex invasive candidiasis, with the exact dose selected by the mycology team.

Pre-hydrate as appropriate and monitor creatinine, potassium, magnesium, blood count and infusion reactions; conventional amphotericin formulations are not dose interchangeable.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Septic shock

Delayed recognition or inadequate source control can rapidly produce refractory circulatory failure, multiorgan injury and death.

Endocarditis

Valve or device seeding causes persistent candidemia, large embolising vegetations and relapse, usually requiring prolonged therapy and surgery.

Ocular candidiasis

Chorioretinitis or endophthalmitis threatens vision and requires agents with ocular penetration, ophthalmic monitoring and sometimes intravitreal therapy.

Deep-organ dissemination

Hepatosplenic, renal, CNS, osteoarticular or other metastatic foci demand targeted imaging, longer treatment and sometimes drainage.

Recurrent resistant infection

Retained biofilm, inadequate penetration or acquired resistance can cause late recurrence, particularly during prolonged C. auris antifungal exposure.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat blood cultures daily or every other day until a documented negative result establishes the clearance date used for duration decisions.
Track haemodynamics, fever, organ function and source-control progress; a falling CRP cannot substitute for clearance cultures and clinical recovery.
Review species and antifungal MICs promptly and repeat susceptibility for breakthrough, recurrence or persistent C. auris because resistance can emerge during exposure.
Monitor liver tests with azoles and echinocandins, renal function and electrolytes with amphotericin, and QT interval and interactions when azoles are used.
Reassess all lines and devices daily and document removal, exchange or the specific reason retention is necessary.
Arrange site-specific follow-up for endocarditis, eye, bone, joint, CNS or hepatosplenic disease and communicate C. auris carriage status at every healthcare transition.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Blood yeast is significant

Candida recovered from a blood culture is not treated as skin contamination; even a single positive bottle demands therapy, source assessment and clearance cultures.

Biomarkers need context

Beta-D-glucan may detect culture-negative disease, but it is shared by several fungi and susceptible to false positivity from healthcare exposures.

Source control changes survival

Removing an infected catheter or draining an abdominal collection is part of definitive treatment because biofilm and devitalised tissue protect yeast from drugs.

Duration starts at clearance

The minimum fourteen-day course for uncomplicated candidemia is counted from the first negative blood culture, not from the first antifungal dose.

AurIs colonisation persists

C. auris may remain on skin and in the environment long after invasive infection resolves, so treatment completion does not automatically end IPC precautions.

11Common pitfallsFrequent interpretation and management errors.

01
Do not dismiss candidemia as a contaminant or wait for species identification before treating an unstable high-risk patient.
02
Do not treat Candida in sputum as pneumonia without invasive evidence; respiratory growth is usually colonisation.
03
Do not use fluconazole automatically before species and susceptibility are known in a critically ill patient or one at risk of resistant species.
04
Do not stop after fourteen calendar days from treatment initiation; uncomplicated duration begins after documented bloodstream clearance and symptom resolution.
05
Do not prescribe antifungal decolonisation for an asymptomatic C. auris carrier, and do not relax contact precautions after antifungal treatment.
06
Do not regard a beta-D-glucan result as a stand-alone species diagnosis or allow it to replace tissue sampling and source control.