scholarly journals Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants

2018 ◽  
Vol 73 (12) ◽  
pp. 3482-3487 ◽  
Author(s):  
Julie Autmizguine ◽  
P Brian Smith ◽  
Kristi Prather ◽  
Catherine Bendel ◽  
Girija Natarajan ◽  
...  

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.

2014 ◽  
Vol 79 (2) ◽  
pp. 280-286 ◽  
Author(s):  
Natalia Andrea Maldonado ◽  
Luz Elena Cano ◽  
Catalina De Bedout ◽  
Carlos Alberto Arbeláez ◽  
Gustavo Roncancio ◽  
...  

2009 ◽  
Vol 249 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Shelley S. Magill ◽  
Sandra M. Swoboda ◽  
Christine E. Shields ◽  
Elizabeth A. Colantuoni ◽  
Annette W. Fothergill ◽  
...  

2018 ◽  
Vol 22 (2) ◽  
pp. 98-105 ◽  
Author(s):  
Claire Hemedez ◽  
Elizabeth Trail-Burns ◽  
Quanfu Mao ◽  
Sharon Chu ◽  
Sunil K Shaw ◽  
...  

Introduction/Objectives Non- albicans Candida species such as Candida parapsilosis and Candida glabrata have emerged as prevalent pathogens in premature infants. The aim of this study was to systematically delineate the histopathologic findings in neonatal non- albicans candidiasis. Methods We performed a retrospective clinicopathologic analysis of extremely premature (23–28 weeks’ gestation) infants diagnosed with invasive candidiasis. Archival autopsy tissues were subjected to periodic acid-Schiff, methenamine-silver and anti- Candida (immuno)histochemical stains, as well as dual anti- Candida and anti-cytokeratin or anti-CD31 immunofluorescence assays. In addition, we studied the prevalence of intestinal Candida colonization in a consecutive autopsy series of extremely premature infants. Results Based on positive postmortem blood and/or lung cultures, invasive candidiasis (3 non- albicans and 11 Candida albicans) was diagnosed in 14 of the 187 extremely premature infants examined between 1995 and 2017. In contrast to the well-known inflammatory and tissue-destructive phenotype of congenital C. albicans infection, invasive non- albicans candidiasis/candidemia caused by C. parapsilosis and C. glabrata was inconspicuous by routine hematoxylin-eosin-based histopathologic analysis despite a heavy fungal presence detected in intestines, lungs, and blood by targeted (immuno)histochemical assays. Intestinal colonization by Candida species was identified in 16 of the 26 (61%) extremely premature neonates who had lived for at least 1 week, as assessed by anti- Candida immunostaining. Conclusion Invasive neonatal non- albicans candidiasis/candidemia appears to have no distinct histopathologic signature. Based on the notoriously low sensitivity of fungal blood cultures and the observed high frequency of Candida intestinal colonization (>50%), it is likely that non- albicans candidiasis/candidemia may be underdiagnosed in (deceased) preterm infants. Routine inclusion of targeted (immuno)histochemical fungal detection strategies in the perinatal autopsy may lead to deeper insight into the prevalence and clinical relevance of neonatal non- albicans candidiasis.


Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2055-2061 ◽  
Author(s):  
Kieren A. Marr ◽  
Kristy Seidel ◽  
Monica A. Slavin ◽  
Raleigh A. Bowden ◽  
H. Gary Schoch ◽  
...  

Two randomized, placebo-controlled trials previously showed that fluconazole (400 mg/d) administered prophylactically decreases the incidence of candidiasis in blood and marrow transplant (BMT) recipients. However, there exists conflicting data regarding the optimal duration of fluconazole administration, specifically whether prophylaxis through acute graft-versus-host disease (GVHD) results in improved survival in allograft recipients. Reported here are the results of long-term follow-up and a detailed analysis of invasive candidiasis and candidiasis-related death in 300 patients who received fluconazole (400 mg/d) or placebo for 75 days after BMT at the Fred Hutchinson Cancer Research Center. Patients in both treatment arms were compared for survival, causes of death, and the incidence of invasive fungal infections early (less than 110 days) and late (more than 110 days) after BMT. After 8 years of follow-up, survival is significantly better in fluconazole recipients compared with placebo recipients (68 of 152 vs 41 of 148,P = .0001). The overall incidence of invasive candidiasis was increased in patients who received placebo compared with fluconazole (30 of 148 vs 4 of 152, P < .001). More patients who received placebo died with candidiasis early (13 of 148 vs 1 of 152, P = .001) and late (8 of 96 vs 1 of 121,P = .0068) after BMT. The incidence of severe GVHD involving the gut was higher in patients who did not receive fluconazole (20 of 143 vs 8 of 145, P = .02), and fewer patients who received fluconazole died with this complication. Thus, administration of fluconazole (400 mg/d) for 75 days after BMT appears to be associated with decreased gut GVHD, a persistent protection against disseminated candidal infections and candidiasis-related death, resulting in an overall survival benefit in allogeneic BMT recipients.


Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2055-2061 ◽  
Author(s):  
Kieren A. Marr ◽  
Kristy Seidel ◽  
Monica A. Slavin ◽  
Raleigh A. Bowden ◽  
H. Gary Schoch ◽  
...  

Abstract Two randomized, placebo-controlled trials previously showed that fluconazole (400 mg/d) administered prophylactically decreases the incidence of candidiasis in blood and marrow transplant (BMT) recipients. However, there exists conflicting data regarding the optimal duration of fluconazole administration, specifically whether prophylaxis through acute graft-versus-host disease (GVHD) results in improved survival in allograft recipients. Reported here are the results of long-term follow-up and a detailed analysis of invasive candidiasis and candidiasis-related death in 300 patients who received fluconazole (400 mg/d) or placebo for 75 days after BMT at the Fred Hutchinson Cancer Research Center. Patients in both treatment arms were compared for survival, causes of death, and the incidence of invasive fungal infections early (less than 110 days) and late (more than 110 days) after BMT. After 8 years of follow-up, survival is significantly better in fluconazole recipients compared with placebo recipients (68 of 152 vs 41 of 148,P = .0001). The overall incidence of invasive candidiasis was increased in patients who received placebo compared with fluconazole (30 of 148 vs 4 of 152, P &lt; .001). More patients who received placebo died with candidiasis early (13 of 148 vs 1 of 152, P = .001) and late (8 of 96 vs 1 of 121,P = .0068) after BMT. The incidence of severe GVHD involving the gut was higher in patients who did not receive fluconazole (20 of 143 vs 8 of 145, P = .02), and fewer patients who received fluconazole died with this complication. Thus, administration of fluconazole (400 mg/d) for 75 days after BMT appears to be associated with decreased gut GVHD, a persistent protection against disseminated candidal infections and candidiasis-related death, resulting in an overall survival benefit in allogeneic BMT recipients.


2020 ◽  
Author(s):  
Dora E Corzo-Leon ◽  
Mark Peacock ◽  
Patricia Rodriguez-Zulueta ◽  
Grace J Salazar-Tamayo ◽  
Donna M MacCallum

Abstract An increasing number of outbreaks due to resistant non-albicans Candida species have been reported worldwide. Between 2014 and 2016, Candida isolates causing invasive candidiasis were recovered in a Mexican hospital. Isolates were identified to species level and antifungal susceptibility was determined. In the time period studied, 74 invasive candidiasis cases were identified, with 38% (28/74) caused by Candida parapsilosis, out of which 54% (15/28) were fluconazole resistant. The ERG11 gene was sequenced for 12 recoverable fluconazole-resistant C. parapsilosis isolates and SNPs identified. The 12 isolates had one common silent point mutation in ERG11 (T591C) and seven isolates had an additional (A395T) mutation, which corresponded to Y132F. Four of the isolates carrying this mutation were closely related within the same cluster by microsatellite typing. This is the first report of an invasive candidiasis outbreak in Mexico due to azole-resistant C. parapsilosis associated with the Y132F substitution.


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