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Candidemia and invasive candidiasis in children: Management

Candidemia and invasive candidiasis in children: Management
Literature review current through: Jan 2024.
This topic last updated: Sep 05, 2023.

INTRODUCTION — The term candidemia describes the presence of Candida species in the blood. Candida in a blood culture should prompt a search for the source; it should never be viewed as a contaminant. Invasive candidiasis encompasses both candidemia and deep-seated (ie, visceral) candidiasis (which may occur with or without candidemia) [1].

The management of candidemia and invasive candidiasis in children will be discussed here. An overview of candidal infections and the clinical manifestations and diagnosis of candidemia and invasive candidiasis in children, candidal infections in neonates, and candidal infections in adults are discussed separately:

(See "Candida infections in children".)

(See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis".)

(See "Epidemiology and risk factors for Candida infection in neonates" and "Clinical manifestations and diagnosis of Candida infection in neonates" and "Treatment of Candida infection in neonates".)

(See "Candidemia in adults: Epidemiology, microbiology, and pathogenesis" and "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults" and "Management of candidemia and invasive candidiasis in adults".)

DOCUMENTED INVASIVE CANDIDIASIS — Treatment of documented candidemia and invasive candidiasis requires treatment with an antifungal agent and adequate source control.

Choice of antifungal therapy — Antifungal therapy should be initiated as soon as possible after Candida is identified in a blood culture or other appropriate laboratory specimens (eg, urine culture, biopsy specimen culture). Early initiation of antifungal therapy (ie, within 24 hours of obtaining blood cultures) is associated with enhanced survival in adult patients with invasive candidiasis [2-4].

The choice of antifungal agent is guided by clinical features (eg, age, hemodynamic stability/severity of illness, site of infection, baseline kidney function) and the infecting Candida species (which affects susceptibility patterns) [5,6]. (See 'Targeted therapy' below.)

Our approach to antifungal therapy in children with invasive candidiasis is generally in keeping with the 2016 Infectious Diseases Society of America (IDSA) and 2012 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of candidiasis (table 1) [7,8]. The treatment of candidiasis in neonates is discussed separately. (See "Treatment of Candida infection in neonates".)

Pending speciation and susceptibility testing — Pending speciation and results of susceptibility testing, the choice of therapy for Candida is influenced by whether the patient is colonized with resistant Candida species, if the patient has developed candidemia despite antifungal prophylaxis, and the proportion of candidemia isolates due to resistant species within a particular medical center. In addition, a positive germ tube test (if performed) suggests Candida albicans (picture 1), which is generally susceptible to fluconazole. When the Candida species and susceptibility are known, antifungal therapy can be adjusted as indicated. (See 'Targeted therapy' below.)

Some additional caveats for particular antifungal classes or agents (see 'Antifungal agents' below):

Echinocandins (eg, micafungin, caspofungin, anidulafungin) are not recommended for candidiasis of the eye, central nervous system (CNS), and urinary tract. They have poor penetration at these sites.

Fluconazole should be avoided in children who are critically ill or are likely to have fluconazole-resistant isolates. Risk factors for fluconazole resistance include neutropenia and recent fluconazole use.

Voriconazole is typically used as step-down therapy in patients with invasive infection due to Candida krusei and fluconazole-resistant, voriconazole-susceptible Candida glabrata.

Considering the caveats above, pending speciation and susceptibility testing, our suggestions for antifungal therapy for particular sites of infection are as follows (table 1) [8]:

Candidemia – An echinocandin or lipid formulation of amphotericin B are the primary therapies. Alternative agents include fluconazole or voriconazole.

Catheter-related thrombophlebitis – An echinocandin or lipid formulation of amphotericin B are the primary therapies. Removal or replacement of the central venous catheter (CVC) is discussed below. (See 'Central venous catheter' below.)

Endocarditis – Lipid formulation of amphotericin B or high-dose echinocandin are the primary therapies. Azole agents are an alternative, but data in children are limited. We add flucytosine for children who receive lipid formulation of amphotericin B or who do not have a clinical response.

Intra-abdominal candidiasis – An echinocandin or lipid formulation of amphotericin B are the primary therapies. Alternative agents include fluconazole or voriconazole.

Hepatosplenic candidiasis – An echinocandin or lipid formulation of amphotericin B are the primary initial therapies. Initial therapy is followed by oral fluconazole if fluconazole resistance is unlikely.

CNS candidiasis – Lipid formulation of amphotericin B is the primary therapy We add flucytosine for children who do not have a clinical response.

Ocular candidiasis – Fluconazole, voriconazole, or lipid formulation of amphotericin B are the primary therapies. We add flucytosine for children who receive lipid formulation of amphotericin B and do not have a clinical response.

Candida pyelonephritis – Lipid formulation of amphotericin B or fluconazole are the primary therapies. Voriconazole is not recommended because the active form is minimally excreted in the urine.

Several large randomized trials in adults have shown that fluconazole is as effective as amphotericin B deoxycholate for the treatment of candidemia [9-12]. Similar comparative randomized trials in children have not been reported, but case reports and noncomparative trials of fluconazole in children suggest that it is safe, well tolerated, and effective [13-15].

Limited data from observational studies also suggest that echinocandins are safe and effective in children [16-23]. Use of echinocandins in children is supported by a multinational observational cohort study that compared echinocandin and azole or amphotericin B therapy in 540 children (>120 days and <18 years) with proven invasive candidiasis outside the CNS [23]. At 14 days, the crude risk of treatment failure was lower in the echinocandin than the azole/amphotericin B group (9.8 versus 13.1 percent); at 30 days, the crude risk of treatment failure was similar (11.1 versus 10.5 percent).

Targeted therapy — Antifungal therapy can be adjusted as indicated when the susceptibility pattern is available and/or the species is identified. In hospitals where susceptibility testing is performed at an outside reference laboratory, prompt adjustment of antifungal therapy (eg, from an echinocandin to fluconazole) may not be feasible.

C. albicans is the most common cause of candidemia, but nonalbicans species are increasingly isolated. Among nonalbicans species, C. glabrata and Candida parapsilosis are most prominent, followed by Candida tropicalis and C. krusei. Antifungal susceptibility patterns and minimal inhibitory concentrations may vary according to species. (See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Epidemiology'.)

C. albicans, C. parapsilosis, and C. tropicalisC. albicans, C. parapsilosis, and C. tropicalis generally are susceptible to amphotericin B, azoles, and echinocandins, and initial therapy with any of these is reasonable for patients with invasive candidiasis that does not involve the eye, CNS, or urinary tract. Echinocandins are not recommended for candidiasis involving the eye, CNS, or urinary tract because they have relatively poor penetration at these sites. Voriconazole is not recommended for candidiasis involving the urinary tract because the active form is minimally excreted in the urine.

For patients with C. albicans, C. parapsilosis, or C. tropicalis isolates that are fluconazole susceptible, we transition from initial antifungal therapy to fluconazole when they are clinically stable.

C. glabrata – For children with invasive candidiasis due to C. glabrata, we usually treat with amphotericin B. Voriconazole may be an alternative for susceptible isolates from sites other than the urinary tract. Many C. glabrata species are resistant to fluconazole. Although echinocandins are preferred for adult patients, some studies have shown increased rates of echinocandin resistance [24-27].

C. krusei – For children with invasive candidiasis due to C. krusei, we usually treat with one of the following:

Amphotericin B – C. krusei may have decreased susceptibility to amphotericin B, requiring higher doses. (See 'Amphotericin B' below.)

An echinocandin, unless the infection involves the eye, CNS, or urinary tract (penetration at these sites is poor).

Voriconazole is an option if the isolate is susceptible and the infection does not involve the urinary tract. Resistance to voriconazole varies geographically. C. krusei is intrinsically resistant to fluconazole.

Source control

Central venous catheter

Children without neutropenia – In addition to prompt initiation of antifungal therapy, CVCs should be removed in nonneutropenic children with candidemia if the catheter is thought to be the source and it can be removed safely. CVCs often are the source of candidemia in patients without neutropenia [28,29].

Children with neutropenia – Although we prefer to remove the CVC as soon as possible in children with neutropenia, the decision is individualized. Factors considered in this decision include the degree to which the child is dependent on central access (eg, for medications, parenteral nutrition), the anticipated difficulty of placing a central line, the possibility that the gastrointestinal tract in the source of invasive candidiasis, and the risk of removing or replacing the CVC.

When feasible, the CVC should be removed as soon as possible [8,30]. Fungemia clears more quickly when CVCs are removed [31,32], and in observational studies, retention of the CVC has been associated with increased mortality in children [29,33,34]. Although successful treatment without CVC removal has been described using antifungal lock therapy in addition to systemic antifungal therapy [35-40], additional studies are necessary before this approach can be routinely recommended.

Other foci of infection — Sources of infection other than a CVC are more common in neutropenic than nonneutropenic patients. Other foci of invasive candidiasis include abscesses or other fluid collections in the abdomen, chest, or bones. In addition to antifungal therapy, successful management of invasive candidiasis requires surgical or interventional radiology procedures to remove or drain these fluid collections [4].

Decisions regarding source control in children with candidal endocarditis or children with candidal pyelonephritis and a nephrostomy tube or stent should be made in consultation with an infectious diseases clinician and the child's cardiologist or nephrologist.

Monitoring response — We obtain daily or every other day blood cultures after initiating treatment for candidemia to confirm the date of sterilization (which determines the duration of treatment). (See 'Duration of antifungal therapy' below.)

Children with invasive candidiasis without candidemia generally are monitored for resolution of signs and symptoms of infection as appropriate (eg, resolution of fever and characteristic lesions on abdominal imaging).

Persistent candidemia — If blood cultures remain positive for more than three days in a patient receiving appropriate antifungal therapy with adequate source control, then a search for a metastatic focus or endocarditis needs to be undertaken:

Patients should be examined for thrombophlebitis or other focal evidence of infection (eg, focal muscle pain, abdominal pain). Signs and symptoms of infection guide the next steps in the evaluation, which often includes advanced imaging techniques (eg, ultrasonography, computed tomography, magnetic resonance imaging), especially in immunocompromised hosts.

An echocardiogram generally is recommended because murmur may be absent in children with endocarditis. (See "Infective endocarditis in children", section on 'Clinical manifestations'.)

Patients with persistent candidemia who have a CVC in place should have the CVC removed. This is discussed in greater detail above. (See 'Central venous catheter' above.)

Duration of antifungal therapy

Suggested duration — The appropriate duration of therapy for invasive candidiasis has not been studied. Our suggested durations are provided below (table 1):

Candidemia – For children with candidemia without neutropenia who have no evidence of metastatic foci of infection, we generally treat for 14 days after the first negative blood culture and resolution of signs and symptoms. This is the duration that has been used in most clinical trials in adults [9] and is the recommended duration in the 2016 IDSA and 2012 ESCMID practice guidelines [7,8].

For children with candidemia and neutropenia, we generally treat for 14 days after the first negative blood culture, resolution of signs and symptoms, and neutrophil count recovery.

CVC-associated candidemia – For patients with CVC-associated candidemia, we generally treat for two weeks after catheter removal and candidemia has cleared.

For patients with CVC-associated candidemia in which catheter retention is attempted, longer durations of therapy generally are needed.

In such cases, performing an ultrasound of large veins to evaluate for thrombophlebitis may be prudent. Patients with Candida suppurative thrombophlebitis require catheter removal and incision and drainage or resection of the vein, if feasible. Antifungal treatment of Candida suppurative thrombophlebitis is generally continued for at least two weeks after candidemia has cleared and preferably when the thrombus has resolved. (See "Candida endocarditis and suppurative thrombophlebitis", section on 'Suppurative thrombophlebitis'.)

Deep-seated invasive candidiasis – For children with deep-seated invasive candidiasis (eg, endocarditis or other metastatic focus of infection), longer durations of therapy are necessary and should be determined in consultation with an infectious diseases clinician.

We typically treat endocarditis for a minimum of six weeks in patients with native value disease, but longer durations may be required in those with complications such as perivalvular abscesses [41]. For patients with prosthetic valve endocarditis caused by Candida species, chronic suppressive antifungal therapy usually is recommended to prevent recurrence. (See "Candida endocarditis and suppurative thrombophlebitis", section on 'Chronic suppressive therapy'.)

Switching to oral therapy — Data regarding when to switch to oral azole therapy in children are lacking. Switching to oral azole therapy may be reasonable in select patients without disseminated infection who are clinically stable, have azole-susceptible isolates and negative repeat blood cultures, and can tolerate oral medication.

EMPIRIC ANTIFUNGAL THERAPY FOR AT-RISK PATIENTS — Empiric antifungal therapy describes provision of antifungal therapy to patients at risk for invasive candidiasis who do not have documented invasive candidiasis, but who may nonetheless have invasive candidiasis, given the low sensitivity of microbiologic tests for Candida. (See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Microbiologic studies'.)

Although empiric antifungal therapy may be life saving in children with false negative mycologic studies, unnecessary use of empiric antifungal therapy may promote antifungal-resistant Candida spp.

Patients with neutropenia – Empiric antifungal therapy may be given routinely to children with neutropenia and fever that have failed to respond to four to five days of antibiotics because they are at substantially increased risk for invasive candidiasis. This is discussed separately. (See "Management of children with non-chemotherapy-induced neutropenia and fever", section on 'Addition of antifungal therapy' and "Fever in children with chemotherapy-induced neutropenia", section on 'Addition of antifungal therapy'.)

Patients without neutropenia – The initiation of empiric antifungal therapy is based on the clinical assessment of the patient in addition to mycologic evidence of invasive candidiasis (eg, polymerase chain reaction [PCR] assay, beta-D-glucan or other antigen assays) and data regarding the patient's colonization status (ie, Candida isolated in cultures from nonsterile sites), if available.

For hospitalized critically ill children without neutropenia who have fever or sepsis not explained by another cause, we initiate empiric antifungal therapy if there is persistent fever (ie, four or five days) and the child has risk factors for invasive candidiasis or known Candida colonization. Risk factors for invasive candidiasis in children include immune suppression, damage to the gastrointestinal mucosa, central venous catheter, broad-spectrum antibiotics, parenteral nutrition, kidney failure requiring hemodialysis, and mechanical ventilation. (See "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Risk factors'.)

When empiric antifungal therapy is warranted, we generally use lipid formulation of amphotericin B or an echinocandin. Echinocandins are not recommended for candidiasis involving the eye, central nervous system, or urinary tract because they have relatively poor penetration at these sites.

In a 2016 meta-analysis of randomized trials in critically ill nonneutropenic patients (predominantly adults), empiric antifungal treatment reduced the risk of proven invasive fungal infection (35.2 versus 64.8 percent; risk ratio 0.57, 95% CI 0.39-0.83; 17 trials, 2024 participants); however, it had no effect on mortality (approximately 24 percent in both groups) [42].

The duration of empiric antifungal therapy in patients without evidence supporting a fungal infection depends upon the clinical response to empiric therapy:

No clinical response – Empiric antifungal therapy should be stopped after four to five days in patients who have no clinical response and lack supporting evidence for fungal infection (ie, negative cultures, negative PCR, negative beta-D-glucan or other antigen assays).

Clinical response – In patients who have a clinical response to therapy but have negative fungal studies (ie, cultures, PCR, beta-D-glucan, other antigen assays), data are lacking about the appropriate duration of antifungal therapy. However, most experts recommend a treatment course for presumptive candidemia (ie, a minimum of two weeks and resolution of signs and symptoms). We agree with this approach.

ANTIFUNGAL AGENTS — Amphotericin B and fluconazole have traditionally been used in the treatment of candidemia in children because of their long-standing safety and efficacy. However, lipid formulations of amphotericin B, other azoles, and echinocandins are increasingly used in children as information about their safety, efficacy, and pharmacokinetics becomes available [43-46].

Amphotericin B

Lipid formulation of amphotericin B — Lipid amphotericin B preparations (eg, liposomal amphotericin B, amphotericin B lipid complex) are preferred for most children, particularly those who are receiving other nephrotoxic agents (eg, posttransplantation) and patients with decreased or decreasing glomerular filtration rate (GFR).

The usual dose is 3 to 5 mg/kg IV once per day; 5 mg/kg per day may be warranted if C. glabrata or C. krusei is suspected or identified.

Although the incidence of decreased kidney function and infusion-related adverse events with lipid formulations of amphotericin B are lower than rates observed with amphotericin B deoxycholate, these complications do occur. Therefore, during therapy with lipid formulations of amphotericin B, we closely monitor serum creatinine and electrolytes, including magnesium and potassium. Serum potassium should be ≥3 mmol/L (3 mEq/L) before administration of lipid formulations of amphotericin B. Daily laboratory monitoring may be required. An alternative antifungal agent (eg, echinocandin, azole) may be needed if there is a rise in serum creatinine or persistent derangement of serum electrolytes.

The pharmacokinetics of lipid formulations in children are similar to those in adults [47]. (See "Pharmacology of amphotericin B", section on 'Lipid-based amphotericin B formulations'.)

Amphotericin B deoxycholate — Most of the experience with treating fungal infections in children has been with amphotericin B deoxycholate (conventional amphotericin). However, use of amphotericin B deoxycholate beyond the neonatal period has fallen out of favor because of drug-associated toxicities.

Although very young children tend to tolerate amphotericin B deoxycholate better than adults and have less nephrotoxicity, we use lipid amphotericin B for most children, particularly those with decreased or decreasing GFR and those receiving other nephrotoxic drugs. GFR can be estimated from height and serum creatinine (calculator 1) [48]. The threshold for choosing lipid amphotericin B is individualized according to the need for other nephrotoxic drugs and trends in GFR over time.

The recommended dose of amphotericin B deoxycholate for infants and children is 1 mg/kg intravenously (IV) per day.

Doses as high as 1.5 mg/kg per day have been used for meningitis or disseminated infection with focal liver or kidney disease, but if higher doses are needed, changing to a lipid formulation may be warranted. (See 'Lipid formulation of amphotericin B' above.)

During therapy with amphotericin B deoxycholate, we closely monitor serum creatinine and electrolytes, including magnesium and potassium. Serum potassium should be ≥3 mmol/L (3 mEq/L) before administration of amphotericin B. Daily laboratory monitoring may be required. Lipid formulations of amphotericin or an echinocandin should be used if there is a rise in serum creatinine [43]. (See "Pharmacology of amphotericin B" and "Amphotericin B nephrotoxicity".)

Echinocandins — Echinocandins include caspofungin, anidulafungin, and micafungin. Echinocandins are an option for primary therapy for children with invasive candidiasis that does not involve they eye, central nervous system, or urinary tract (echinocandins have relatively poor penetration at these sites).

Echinocandins are first-line agents for the treatment of invasive candidiasis in adults, based upon randomized trials demonstrating that they are as safe and effective as amphotericin B or fluconazole [49-52]. Although data in children are limited, echinocandins appear to be safe and effective [16-23].

General dosing guidelines for echinocandins in children are as provided below [17,53-58]. Before starting therapy, consultation with an infectious diseases pharmacist or clinician may be warranted.

Caspofungin – Caspofungin is available for the treatment of candidemia and invasive candidiasis in children ≥3 months of age. It is also available for empiric treatment of suspected fungal infection in children ≥3 months of age with fever and neutropenia. Caspofungin is dosed by body surface area (BSA) rather than weight. The BSA is calculated from the child's height and weight using a nomogram or calculator (calculator 2) [17,18,59,60]:

The recommended regimen is a single loading dose of 70 mg/m2 per day (maximum dose 70 mg) IV, followed by 50 mg/m2 per day (maximum dose 70 mg) IV.

Patients receiving other medications that induce drug clearance (eg, phenytoin, rifampin) may require increased doses (within the maximum dose of 70 mg).

Micafungin

For patients ≥4 months of age, micafungin is available for the treatment of candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses, esophageal candidiasis, and prophylaxis of Candida infections in patients undergoing hematopoietic cell transplantation [61].

The suggested dose varies according to the indication and clinical response. For the treatment of candidemia and invasive candidiasis, the initial dose is 2 mg/kg IV once daily (maximum 100 mg per day). Increased doses (up to 10 mg/kg per day) may be necessary in children <40 kg or those without an adequate clinical response to a lower dose [8,62,63].

For infants <4 months of age, micafungin is available for the treatment of candidemia, acute disseminated candidiasis, and Candida peritonitis and abscesses, provided that the infants do not have meningoencephalitis and/or ocular dissemination [61].

The suggested dose is 4 mg/kg IV once daily [61]. Based on limited data, increased doses (up to 10 mg/kg per day) may be necessary for infants who do not respond to lower doses [62,63].

Anidulafungin – For patients ≥1 month of age, anidulafungin is available for the treatment of candidemia, intra-abdominal abscess, and peritonitis [64].

The recommended regimen is a single loading dose of 3 mg/kg IV (maximum dose 200 mg) on day 1, followed by 1.5 mg/kg IV once daily (maximum dose 100 mg) for at least 14 days after the last positive culture [64].

Azole antifungal agents — Azole antifungal agents available for the treatment of candidemia and invasive candidiasis in children include fluconazole and voriconazole. The safety and efficacy of other azole antifungal agents (eg, posaconazole, isavuconazole) in the treatment of invasive candidiasis in children have not been adequately studied.

Fluconazole – Fluconazole is used more often than voriconazole in the treatment of invasive candidiasis in children. Fluconazole should be avoided in children who are critically ill or are likely to have fluconazole-resistant isolates. Risk factors for fluconazole resistance include neutropenia and recent fluconazole use. Fluconazole should not be used if C. krusei is suspected or identified. C. krusei is intrinsically resistant to fluconazole [65].

The recommended dose of fluconazole for children is 12 mg/kg IV per day [66].

Children require higher doses of fluconazole than adults because the half-life is shorter in children [66,67].

Voriconazole – Voriconazole generally is used as step-down therapy in patients with invasive infection due to C. krusei and fluconazole-resistant, voriconazole-susceptible C. glabrata.

Voriconazole is not recommended for patients with urinary candidiasis because the active form is minimally excreted in the urine.

The recommended dose of voriconazole for children varies according to age [68,69]:

<12 years – 9 mg/kg IV twice daily as a loading dose for the first day and then 8 mg/kg every 12 hours

≥12 years – 6 mg/kg IV twice daily as a loading dose for the first day and then 4 mg/kg every 12 hours

Younger children require higher doses of voriconazole than older children and adults because of differing elimination patterns (linear elimination until approximately 12 years of age and nonlinear elimination thereafter) [68].

We monitor serum voriconazole concentrations and adjust the dose to maintain trough concentration between 1 and 5 mcg/mL [70-72]. Trough concentrations >5 mcg/mL are associated with toxicity [71,72]. In observational studies, the pharmacokinetics of voriconazole have varied markedly from patient to patient [73-76]. In one study, voriconazole trough concentrations of >1 mcg/mL were associated with increased survival from invasive fungal infection (9 of 46 children had invasive candidiasis) [73]. Pending prospective studies confirming these results, it is prudent to maintain a trough concentration of at least 1 mcg/mL.

OUTCOME — Untreated candidemia has a mortality rate of over 60 percent [77]. With treatment, the overall mortality of candidemia in children ranges from 9 to 40 percent [78-80].

Factors associated with increased mortality include [2-4,78,81,82]:

Delayed initiation or inadequate dosing of antifungal therapy

Septic shock

Inadequate source control (ie, failure to remove a central venous catheter or to drain or surgically remove a deep-seated source)

Increased severity of illness (eg, as determined by a validated scoring system)

Infection with an antifungal-resistant strain

Immunosuppressive therapy

The infecting Candida species (C. albicans and C. glabrata have increased mortality compared with C. parapsilosis)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Candidiasis".)

SUMMARY AND RECOMMENDATIONS

Introduction – The term candidemia describes the presence of Candida species in the blood. Candida in a blood culture should prompt a search for the source; it should never be viewed as a contaminant. (See 'Introduction' above.)

Treatment of documented invasive candidiasis

Choice of antifungal therapy – Antifungal therapy should be initiated as soon as possible after Candida is identified in a blood culture. The choice of antifungal agent is guided by clinical features (age, hemodynamic stability/severity of illness, site of infection, baseline kidney function, neutropenia) and the infecting Candida species (table 1). (See 'Choice of antifungal therapy' above.)

Source control

-Children without neutropenia – We remove central venous catheters (CVCs) in nonneutropenic children with candidemia if the catheter is thought to be the source and it can be removed safely. (See 'Source control' above.)

-Children with neutropenia – We prefer to remove the CVC as soon as possible in children with neutropenia. However, the decision is individualized. Factors considered in this decision include the degree to which the child is dependent on central access (eg, for medications, parenteral nutrition), the anticipated difficulty of placing a central line, the possibility that the gastrointestinal tract in the source of invasive candidiasis, and the risk of removing or replacing the CVC. (See 'Source control' above.)

Monitoring response – We obtain daily or every other day blood cultures after initiating treatment for invasive candidiasis to confirm the date of sterilization, which affects the duration of treatment. (See 'Monitoring response' above.)

Duration of therapy – For children with candidemia and no evidence of metastatic foci of infection, we generally treat for a minimum of two weeks after blood cultures become negative (table 1).

For children with deep-seated invasive candidiasis (eg, endocarditis or other metastatic focus of infection), longer durations of therapy are necessary and should be determined in consultation with an infectious diseases clinician. (See 'Duration of antifungal therapy' above.)

Empiric antifungal therapy for at-risk patients – For hospitalized critically ill children without neutropenia who have fever or sepsis not explained by another cause, we initiate empiric antifungal therapy if there is persistent fever (ie, four or five days) and the child has risk factors for invasive candidiasis or known Candida colonization. Risk factors for invasive candidiasis in children include immune suppression, damage to the gastrointestinal mucosa, CVC, broad-spectrum antibiotics, parenteral nutrition, kidney failure requiring hemodialysis, and mechanical ventilation. (See 'Empiric antifungal therapy for at-risk patients' above.)

Outcome – Even with appropriate therapy, the mortality of candidemia ranges from 9 to 40 percent. Factors associated with increased mortality include delayed initiation or inadequate dosing of antifungal therapy, inadequate source control, increased severity of illness, and immunosuppressive therapy. (See 'Outcome' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Carol A Kauffman, MD, who contributed to an earlier version of this topic review.

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Topic 6014 Version 29.0

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