Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants

Julie Autmizguine, P. Brian Smith, Kristi Prather, Catherine M Bendel, Girija Natarajan, Margarita Bidegain, David A. Kaufman, David J. Burchfield, Ashley S. Ross, Paresh Pandit, Wiley A. Schell, Jamie Gao, Daniel K. Benjamin, Scott Macgilvray, Kelly Wade, Rune Toms, Neil Finer, Dan Stewart, Antonio Arrieta, Shahnaz Duara & 18 others Seetha Shankaran, Jonathan Nedrelow, Robert White, Anand Kantak, Karen Shattuck, Mohan Pammi, Kathleen Kennedy, Pablo Sanchez, Ramasubbareddy Dhanireddy, Barry Bloom, Mark Hudak, Agnes Perenyi, Natalie Neu, Echezona Ezeanolue, Roger Kim, Gratias Mundakel, Brenda Poindexter, Phillip Gordon

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. Methods We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates. Results Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P < 0.001) and 2 (3% versus 27%; P < 0.001). After the baseline period, two infants (1%) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate. Conclusions Fluconazole prophylaxis decreased Candida albicans and € non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.

Original languageEnglish (US)
Pages (from-to)3482-3487
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number12
DOIs
StatePublished - Dec 1 2018

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Fluconazole
Candida
Premature Infants
Invasive Candidiasis
Placebos
Extremely Premature Infants
Candida albicans
Birth Weight
Randomized Controlled Trials

PubMed: MeSH publication types

  • Journal Article

Cite this

Autmizguine, J., Smith, P. B., Prather, K., Bendel, C. M., Natarajan, G., Bidegain, M., ... Gordon, P. (2018). Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants. Journal of Antimicrobial Chemotherapy, 73(12), 3482-3487. https://doi.org/10.1093/jac/dky353

Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants. / Autmizguine, Julie; Smith, P. Brian; Prather, Kristi; Bendel, Catherine M; Natarajan, Girija; Bidegain, Margarita; Kaufman, David A.; Burchfield, David J.; Ross, Ashley S.; Pandit, Paresh; Schell, Wiley A.; Gao, Jamie; Benjamin, Daniel K.; Macgilvray, Scott; Wade, Kelly; Toms, Rune; Finer, Neil; Stewart, Dan; Arrieta, Antonio; Duara, Shahnaz; Shankaran, Seetha; Nedrelow, Jonathan; White, Robert; Kantak, Anand; Shattuck, Karen; Pammi, Mohan; Kennedy, Kathleen; Sanchez, Pablo; Dhanireddy, Ramasubbareddy; Bloom, Barry; Hudak, Mark; Perenyi, Agnes; Neu, Natalie; Ezeanolue, Echezona; Kim, Roger; Mundakel, Gratias; Poindexter, Brenda; Gordon, Phillip.

In: Journal of Antimicrobial Chemotherapy, Vol. 73, No. 12, 01.12.2018, p. 3482-3487.

Research output: Contribution to journalArticle

Autmizguine, J, Smith, PB, Prather, K, Bendel, CM, Natarajan, G, Bidegain, M, Kaufman, DA, Burchfield, DJ, Ross, AS, Pandit, P, Schell, WA, Gao, J, Benjamin, DK, Macgilvray, S, Wade, K, Toms, R, Finer, N, Stewart, D, Arrieta, A, Duara, S, Shankaran, S, Nedrelow, J, White, R, Kantak, A, Shattuck, K, Pammi, M, Kennedy, K, Sanchez, P, Dhanireddy, R, Bloom, B, Hudak, M, Perenyi, A, Neu, N, Ezeanolue, E, Kim, R, Mundakel, G, Poindexter, B & Gordon, P 2018, 'Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants', Journal of Antimicrobial Chemotherapy, vol. 73, no. 12, pp. 3482-3487. https://doi.org/10.1093/jac/dky353
Autmizguine, Julie ; Smith, P. Brian ; Prather, Kristi ; Bendel, Catherine M ; Natarajan, Girija ; Bidegain, Margarita ; Kaufman, David A. ; Burchfield, David J. ; Ross, Ashley S. ; Pandit, Paresh ; Schell, Wiley A. ; Gao, Jamie ; Benjamin, Daniel K. ; Macgilvray, Scott ; Wade, Kelly ; Toms, Rune ; Finer, Neil ; Stewart, Dan ; Arrieta, Antonio ; Duara, Shahnaz ; Shankaran, Seetha ; Nedrelow, Jonathan ; White, Robert ; Kantak, Anand ; Shattuck, Karen ; Pammi, Mohan ; Kennedy, Kathleen ; Sanchez, Pablo ; Dhanireddy, Ramasubbareddy ; Bloom, Barry ; Hudak, Mark ; Perenyi, Agnes ; Neu, Natalie ; Ezeanolue, Echezona ; Kim, Roger ; Mundakel, Gratias ; Poindexter, Brenda ; Gordon, Phillip. / Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants. In: Journal of Antimicrobial Chemotherapy. 2018 ; Vol. 73, No. 12. pp. 3482-3487.
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title = "Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants",
abstract = "Objectives Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. Methods We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates. Results Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5{\%} versus 27{\%}; P < 0.001) and 2 (3{\%} versus 27{\%}; P < 0.001). After the baseline period, two infants (1{\%}) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate. Conclusions Fluconazole prophylaxis decreased Candida albicans and € non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.",
author = "Julie Autmizguine and Smith, {P. Brian} and Kristi Prather and Bendel, {Catherine M} and Girija Natarajan and Margarita Bidegain and Kaufman, {David A.} and Burchfield, {David J.} and Ross, {Ashley S.} and Paresh Pandit and Schell, {Wiley A.} and Jamie Gao and Benjamin, {Daniel K.} and Scott Macgilvray and Kelly Wade and Rune Toms and Neil Finer and Dan Stewart and Antonio Arrieta and Shahnaz Duara and Seetha Shankaran and Jonathan Nedrelow and Robert White and Anand Kantak and Karen Shattuck and Mohan Pammi and Kathleen Kennedy and Pablo Sanchez and Ramasubbareddy Dhanireddy and Barry Bloom and Mark Hudak and Agnes Perenyi and Natalie Neu and Echezona Ezeanolue and Roger Kim and Gratias Mundakel and Brenda Poindexter and Phillip Gordon",
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TY - JOUR

T1 - Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants

AU - Autmizguine, Julie

AU - Smith, P. Brian

AU - Prather, Kristi

AU - Bendel, Catherine M

AU - Natarajan, Girija

AU - Bidegain, Margarita

AU - Kaufman, David A.

AU - Burchfield, David J.

AU - Ross, Ashley S.

AU - Pandit, Paresh

AU - Schell, Wiley A.

AU - Gao, Jamie

AU - Benjamin, Daniel K.

AU - Macgilvray, Scott

AU - Wade, Kelly

AU - Toms, Rune

AU - Finer, Neil

AU - Stewart, Dan

AU - Arrieta, Antonio

AU - Duara, Shahnaz

AU - Shankaran, Seetha

AU - Nedrelow, Jonathan

AU - White, Robert

AU - Kantak, Anand

AU - Shattuck, Karen

AU - Pammi, Mohan

AU - Kennedy, Kathleen

AU - Sanchez, Pablo

AU - Dhanireddy, Ramasubbareddy

AU - Bloom, Barry

AU - Hudak, Mark

AU - Perenyi, Agnes

AU - Neu, Natalie

AU - Ezeanolue, Echezona

AU - Kim, Roger

AU - Mundakel, Gratias

AU - Poindexter, Brenda

AU - Gordon, Phillip

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Objectives Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. Methods We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates. Results Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P < 0.001) and 2 (3% versus 27%; P < 0.001). After the baseline period, two infants (1%) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate. Conclusions Fluconazole prophylaxis decreased Candida albicans and € non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.

AB - Objectives Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. Methods We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates. Results Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P < 0.001) and 2 (3% versus 27%; P < 0.001). After the baseline period, two infants (1%) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate. Conclusions Fluconazole prophylaxis decreased Candida albicans and € non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.

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U2 - 10.1093/jac/dky353

DO - 10.1093/jac/dky353

M3 - Article

VL - 73

SP - 3482

EP - 3487

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

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