Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants

Autmizguine, Julie; Smith, Patrick B.; Prather, Kristi; Natarajan, Girija; Kaufman, David; Schell, Wiley A.; Gao, Junheng; Benjamin, Daniel K.; MacGilvray, Scott; Wade, Kelly C.; Bidegain, Margarita; Toms, Rune; Finer, Neil N.; Burchfield, David J.; Stewart, Dan L.; Arrieta, Antonio; Duara, Shahnaz; Shankaran, Seetha; Nedrelow, Jonathan; White, Robert D.; Kantak, Anand; Shattuck, Karen E.; Pammi, Mohan; Kennedy, Kathleen A.; Sánchez, Pablo J.; Bendel, Catherine M.; Dhanireddy, Ramasubbareddy; Bloom, Barry T.; Perenyi, Agnes; Neu, Natalie; Ezeanolue, Echezona E.; Kim, Roger H.; Hudak, Mark L.; Mundakel, Gratias; Pandit, Paresh B.; Ross, Ashley; Poindexter, Brenda B.; Gordon, Phillip V.

doi:10.1093/jac/dky353

Cited by 32 publications

(24 citation statements)

References 23 publications

(41 reference statements)

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“…14 Kaufman et al furthermore demonstrated a slight increase of the minimal inhibitory concentration (MIC) in Candida strains colonizing neonates admitted in a randomized clinical trial of fluconazole prophylaxis. 15 A slightly different experience had been described by Sarvikivi et al in their NICU in Finland: in a 12-year period, they did not detect any increase of C. glabrata or C. krusei (while using the fluconazole prophylaxis); however, they observed the appearance of resistance in some strains of C. parapsilosis, that were originally sensitive to fluconazole. It is important to notice that this event happened when they extended the prophylaxis to all the neonates admitted to the NICU instead of reserving it to high-risk subgroups such as VLBW or ELBW neonates.…”

Section: Discussionmentioning

confidence: 82%

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains

et al. 2019

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Objective We analyzed the fungal ecology of a neonatal intensive care unit (NICU) over a period of 20 consecutive years following the introduction of routine fluconazole prophylaxis for all very low birth weight (VLBW; <1,500 g at birth) preterm babies. The aim was to detect the possible appearance of any ecological shifts toward the emergence of native fluconazole-resistant (NFR) fungal species. Study Design This was a retrospective analysis of clinical and microbiological data of VLBW preterm neonates admitted to a large tertiary NICU in Italy from 1997 to 2016 and surviving more than 3 days. Colonization and infection incidence rates, both for fluconazole-sensitive Candida spp and NFR Candida spp, were calculated for each year. We compared the first 4-year period without prophylaxis (1997–2000) with the last 16-year period with use of routine fluconazole prophylaxis (2000–2016). Results Overall, the incidence of fungal colonization significantly decreased after the introduction of prophylaxis (from 43.4% to 16.5%) as well as the systemic fungal infection incidence (from 16% to 3.7%). The proportion of colonization and infection by NFR Candida spp, on the other hand, did not increase, remaining stable throughout the 16 years of exposure to fluconazole. During the prophylaxis period, 42 of 1,172 VLBW neonates were colonized by NFR species (3.6%), and of them 11 developed a systemic infection (0.9%). During the preprophylaxis period, colonization by these particular species affected 11 of 285 VLBW neonates (3.8%), and a systemic infection involved 4 neonates (1.4%). Conclusion Fluconazole prophylaxis is effective in decreasing Candida colonization and systemic infections in preterm neonates in NICU and did not cause emergence or shifts toward NFR Candida spp over a 16-year surveillance period.

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Section: Discussionmentioning

confidence: 82%

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains

et al. 2019

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“…The incorporation of a loading dose is consistent with previous findings and is often currently used in clinical practice . The MIC of 8 mg/L used in these simulations likely provides a conservative estimate given that the actual MIC values measured during the prophylaxis study were 0.25–1 mg/L . A follow‐up study of Candida susceptibility to fluconazole found that only 4% of isolates were resistant, further supporting the efficacy of fluconazole when using the proposed dosing regimen .…”

Section: Discussionmentioning

confidence: 89%

“…Throughout the prophylaxis study, Candida isolates were collected at study days 0–7, study days 8–28, and study days 29–49 . MIC values were tested using the Clinical and Laboratory Standards Institute method for all positive Candida cultures .…”

Section: Methodsmentioning

confidence: 99%

Physiologically‐Based Pharmacokinetic Modeling of Fluconazole Using Plasma and Cerebrospinal Fluid Samples From Preterm and Term Infants

Gerhart

Watt

Edginton

et al. 2019

CPT Pharmacom & Syst Pharma

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Fluconazole is used to treat hematogenous Candida meningoencephalitis in preterm and term infants. To characterize plasma and central nervous system exposure, an adult fluconazole physiologically‐based pharmacokinetic (PBPK) model was scaled to infants, accounting for age dependencies in glomerular filtration and metabolism. The model was optimized using 760 plasma samples from 166 infants (median postmenstrual age (range) 28 weeks (24–50)) and 27 cerebrospinal fluid ( CSF ) samples from 22 infants ( postmenstrual age 28 weeks (24–33)). Simulations evaluated achievement of the surrogate efficacy target of area under the unbound concentration‐time curve ≥ 400 mg • hour/L over the dosing interval in plasma and CSF using dosing guidelines. Average fold error of predicted concentrations was 0.73 and 1.14 for plasma and CSF , respectively. Target attainment in plasma and CSF was reached faster after incorporating a loading dose of 25 mg/kg. PBPK modeling can be useful in exploring CNS kinetics of drugs in children.

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“…biofilm [ 57 ]; C. krusei possesses an intrinsic resistance to azoles and C. glabrata is less susceptible to them [ 66 ]. Additionally, the emerging resistance to this group of drugs among isolates of Candida spp., especially C. auris , C. parapsilosis and C. tropicalis is currently observed [ 54 , 70 ] as a consequence of the massive preventive application of fluconazole [ 71 , 72 ] and common use of agricultural fungicides, structurally similar to azoles [ 73 ]. The resistance relies on the mutations or overexpression of ERG11 and ERG3 genes, which lead to increased tolerance to methylated sterols and overexpression of drug-efflux pumps that transport azoles outside of the fungal cell [ 65 , 67 ].…”

Section: Current Methods For Treatment and Management Of Superficimentioning

confidence: 99%

Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

Guevara-Lora

Bras

Karkowska‐Kuleta

et al. 2020

IJMS

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Yeast-like fungi from the Candida genus are predominantly harmless commensals that colonize human skin and mucosal surfaces, but under conditions of impaired host immune system change into dangerous pathogens. The pathogenicity of these fungi is typically accompanied by increased adhesion and formation of complex biofilms, making candidal infections challenging to treat. Although a variety of antifungal drugs have been developed that preferably attack the fungal cell wall and plasma membrane, these pathogens have acquired novel defense mechanisms that make them resistant to standard treatment. This causes an increase in the incidence of candidiasis and enforces the urgent need for an intensified search for new specifics that could be helpful, alone or synergistically with traditional drugs, for controlling Candida pathogenicity. Currently, numerous reports have indicated the effectiveness of plant metabolites as potent antifungal agents. These substances have been shown to inhibit growth and to alter the virulence of different Candida species in both the planktonic and hyphal form and during the biofilm formation. This review focuses on the most recent findings that provide evidence of decreasing candidal pathogenicity by different substances of plant origin, with a special emphasis on the mechanisms of their action. This is a particularly important issue in the light of the currently increasing frequency of emerging Candida strains and species resistant to standard antifungal treatment.

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Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants

Abstract: Fluconazole prophylaxis decreased Candida albicans and 'non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.

Cited by 32 publications

References 23 publications

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains

Physiologically‐Based Pharmacokinetic Modeling of Fluconazole Using Plasma and Cerebrospinal Fluid Samples From Preterm and Term Infants

Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

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