Fungal infections and antifungal prophylaxis in pediatric cardiac extracorporeal life support

Gardner, Aimee; Prodhan, Parthak; Stovall, Stephanie H.; Gossett, Jeffrey M.; Stern, Jennie; Wilson, Christopher D.; Fiser, Richard T.

doi:10.1016/j.jtcvs.2011.12.001

Cited by 36 publications

(29 citation statements)

References 24 publications

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“…6 For the purposes of the current study, only the final version was used 6 ; however, neither is included in the nine studies used for systematic review.…”

Section: Literature Searchmentioning

confidence: 99%

“…2,[7][8][9][10][11][12][13] Four of these studies were ELSO centers and may have analyzed data included in the ELSO registry study. [6][7][8][9] The other studies also took place during the ELSO period and may be, at least in part, included in the registry study. Six provided information regarding the total days supported on ECMO and were used to calculate rates of infections.…”

Section: Study Detailsmentioning

confidence: 99%

“…Gardner et al 6 evaluated the prevalence of fungal infections in patients receiving ECMO primarily for cardiac support. In that study, a fungal infection developed in 12% of patients, with surgical site infections reported most commonly.…”

Section: Rates Of Infectionmentioning

confidence: 99%

See 2 more Smart Citations

The Evidence Base for Prophylactic Antibiotics in Patients Receiving Extracorporeal Membrane Oxygenation

O’Horo¹,

Cawcutt²,

Moraes³

et al. 2016

ASAIO Journal

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The aim of this review was to evaluate evidence for the use of antibiotic prophylaxis in patients receiving extracorporeal membrane oxygenation (ECMO) therapy. We systematically reviewed MEDLINE, EMBASE, Scopus, and other major databases and included any study that reported rates of infection and whether antibiotic prophylaxis was a part of therapy for patients receiving ECMO. We abstracted rates of infection, microbiology of isolates, prophylactic practices, and individual study inclusion and exclusion criteria. Among 11 studies identified, rates of infection were fairly uniform regardless of prophylaxis use, and the only two studies that directly compared outcomes with and without prophylaxis found no benefit. The causative infectious organisms were heterogeneous, which gives no clear rationale for any particular prophylactic strategy. Although infections during ECMO are serious complications that must be prevented, there is no good evidence to support routine use of prophylactic antibiotics in most patients. Certain subpopulations, such as those with open chests, may have an indication for prophylaxis, but evidence is poor. Future studies should investigate the role of other approaches to infection prevention, such as chlorhexidine bathing and preferential elective cannulation.

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“…6 For the purposes of the current study, only the final version was used 6 ; however, neither is included in the nine studies used for systematic review.…”

Section: Literature Searchmentioning

confidence: 99%

Section: Study Detailsmentioning

confidence: 99%

See 1 more Smart Citation

The Evidence Base for Prophylactic Antibiotics in Patients Receiving Extracorporeal Membrane Oxygenation

O’Horo¹,

Cawcutt²,

Moraes³

et al. 2016

ASAIO Journal

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“…In this population, Candida species are the most common infectious organism (2). The incidence of infection varies by center, and rates as high as 10% have been reported (2,3). Candida infections cause substantial morbidity and mortality (3) and are difficult to eradicate due to the ability of the organism to adhere to indwelling catheters.…”

mentioning

confidence: 99%

“…The incidence of infection varies by center, and rates as high as 10% have been reported (2,3). Candida infections cause substantial morbidity and mortality (3) and are difficult to eradicate due to the ability of the organism to adhere to indwelling catheters. For this reason, routine management of candidiasis consists not only of the use of antifungal agents but also the removal of catheters (4).…”

mentioning

confidence: 99%

Fluconazole Population Pharmacokinetics and Dosing for Prevention and Treatment of Invasive Candidiasis in Children Supported with Extracorporeal Membrane Oxygenation

Watt

González

Benjamin

et al. 2015

Antimicrob Agents Chemother

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f Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal drug exposures. The objective of our study was to determine the PK of fluconazole in children on ECMO. Forty children with 367 PK samples were included in the analysis. The PK data were analyzed using nonlinear mixed-effect modeling (NONMEM). A one-compartment model best described the data. Weight was included in the base model for clearance ( Extracorporeal membrane oxygenation (ECMO) is life-saving in children with refractory cardiorespiratory failure. ECMO is a cardiopulmonary bypass device that provides complete respiratory and cardiac support. Mechanically, blood is drained from the venous system, pumped through an artificial lung membrane in which oxygen is added and carbon dioxide is removed, and then returned to either venous or arterial circulation. ECMO has been used successfully to support children with multiple disease processes, including meconium aspiration syndrome, fulminant myocarditis, and sepsis (1). Despite these successes, children supported by ECMO are at high risk for ECMO-related complications, especially nosocomial infections (2).Invasive candidiasis is common and fatal in children on ECMO. In this population, Candida species are the most common infectious organism (2). The incidence of infection varies by center, and rates as high as 10% have been reported (2, 3). Candida infections cause substantial morbidity and mortality (3) and are difficult to eradicate due to the ability of the organism to adhere to indwelling catheters. For this reason, routine management of candidiasis consists not only of the use of antifungal agents but also the removal of catheters (4). Catheter removal for children on ECMO is often impossible, because the ECMO cannulas connect the child to the ECMO circuit. Therefore, therapy on ECMO relies on either the prevention of invasive candidiasis or optimal therapeutic dosing in children with infection.Optimal dosing for prevention or treatment of candidiasis in children on ECMO can differ greatly from that with other populations due to the pharmacokinetic (PK) changes induced by the ECMO circuit. PK changes attributed to ECMO support include increased volume of distribution (V) and decreased clearance (CL), but these vary by drug and are not consistently predicted using drug physicochemical properties (5-8). This study describes the population PK of fluconazole in children supported by ECMO and provides rational dosing recommendations for the prevention and treatment of invasive candidiasis in this vulnerable population. MATERIALS AND METHODSStudy design. Fluconazole samples were obtained from three prospective trials. Study 1 was a single-center open-label PK study of fluconazole in children on ECMO (n ϭ 20) (9), study 2 was a single-center PK study of a fluconazole loading dose in critically ill children (n...

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Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support: Fluconazole in Children on ECMO

Watt

Cohen‐Wolkowiez

Barrett

et al. 2018

CPT Pharmacom & Syst Pharma

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Extracorporeal life support (e.g., dialysis, extracorporeal membrane oxygenation (ECMO)) can affect drug disposition, placing patients at risk for therapeutic failure. In this population, dose selection to achieve safe and effective drug exposure is difficult. We developed a novel and flexible approach that uses physiologically based pharmacokinetic (PBPK) modeling to translate results from ECMO ex vivo experiments into bedside dosing recommendations. To determine fluconazole dosing in children on ECMO, we developed a PBPK model, which was validated using fluconazole pharmacokinetic (PK) data in adults and critically ill infants. Next, an ECMO compartment was added to the PBPK model and parameterized using data from a previously published ex vivo study. Simulations using the final ECMO PBPK model reasonably characterized observed PK data in infants on ECMO, and the model was used to derive dosing in children on ECMO across the pediatric age spectrum. This approach can be generalized to other forms of extracorporeal life support (ECLS), such as dialysis.

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Fungal infections and antifungal prophylaxis in pediatric cardiac extracorporeal life support

Abstract: Children with cardiac disease supported with ECMO who acquire fungal infections have increased mortality. Routine fluconazole prophylaxis is associated with lower rates of fungal infections in these patients.

Cited by 36 publications

References 24 publications

The Evidence Base for Prophylactic Antibiotics in Patients Receiving Extracorporeal Membrane Oxygenation

The Evidence Base for Prophylactic Antibiotics in Patients Receiving Extracorporeal Membrane Oxygenation

Fluconazole Population Pharmacokinetics and Dosing for Prevention and Treatment of Invasive Candidiasis in Children Supported with Extracorporeal Membrane Oxygenation

Physiologically Based Pharmacokinetic Approach to Determine Dosing on Extracorporeal Life Support: Fluconazole in Children on ECMO

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