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Meta-Analysis
. 2015 Oct 24;2015(10):CD003478.
doi: 10.1002/14651858.CD003478.pub5.

Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants

Nicola Austin  1 , Jemma Cleminson, Brian A Darlow, William McGuire
Affiliations
Meta-Analysis

Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants

Nicola Austin et al. Cochrane Database Syst Rev. .

Abstract

Background: Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population.

Objectives: To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants.

Search methods: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2015, Issue 7), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews.

Selection criteria: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants.

Data collection and analysis: We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors.

Main results: Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio 0.20, 95% confidence interval 0.14 to 0.27; risk difference -0.18, -0.21 to -0.15) but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality (typical risk ratio 0.87, 0.72 to 1.05; risk difference -0.03, -0.06 to 0.01). None of the trials assessed posthospital discharge outcomes. Three trials (N = 326) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality.

Authors' conclusions: The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.

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Conflict of interest statement

None.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Forest plot of comparison: 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, outcome: 1.1 Incidence of invasive fungal infection.
3
3
Forest plot of comparison: 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, outcome: 1.2 Mortality.
4
4
Forest plot of comparison: 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, outcome: 1.6 Length of stay in NICU (days).
5
5
Forest plot of comparison: 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, outcome: 2.1 Incidence of invasive fungal infection.
6
6
Forest plot of comparison: 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, outcome: 2.2 Mortality.
7
7
Forest plot of comparison: 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, outcome: 2.4 Necrotising enterocolitis.
1.1
1.1. Analysis
Comparison 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, Outcome 1 Incidence of invasive fungal infection.
1.2
1.2. Analysis
Comparison 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, Outcome 2 Mortality.
1.3
1.3. Analysis
Comparison 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, Outcome 3 Bronchopulmonary dysplasia.
1.4
1.4. Analysis
Comparison 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, Outcome 4 Necrotising enterocolitis.
1.5
1.5. Analysis
Comparison 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, Outcome 5 Retinopathy of prematurity.
1.6
1.6. Analysis
Comparison 1 Oral/topical non‐absorbed antifungal prophylaxis vs placebo or nothing, Outcome 6 Length of stay in NICU (days).
2.1
2.1. Analysis
Comparison 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, Outcome 1 Incidence of invasive fungal infection.
2.2
2.2. Analysis
Comparison 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, Outcome 2 Mortality.
2.3
2.3. Analysis
Comparison 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, Outcome 3 Bronchopulmonary dysplasia.
2.4
2.4. Analysis
Comparison 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, Outcome 4 Necrotising enterocolitis.
2.5
2.5. Analysis
Comparison 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, Outcome 5 Retinopathy of prematurity.
2.6
2.6. Analysis
Comparison 2 Oral/topical non‐absorbed prophylaxis vs. systemic antifungal prophylaxis, Outcome 6 Length of stay in NICU (days).
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Update of

References

References to studies included in this review

Aydemir 2011a {published data only}
    1. Aydemir C, Oguz SS, Dizdar EA, Akar M, Sarikabadayi YU, Saygan S, et al. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2011;96(3):F164‐8. [PUBMED: 20659937] - PubMed
Aydemir 2011b {published data only}
    1. Aydemir C, Oguz SS, Dizdar EA, Akar M, Sarikabadayi YU, Saygan S, et al. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2011;96(3):F164‐8. [PUBMED: 20659937] - PubMed
Mersal 2013 {published data only}
    1. Mersal A, Alzahrani I, Azzouz M, Alsubhi A, Alsawaigh H, Albshri N, et al. Oral nystatin versus intravenous fluconazole as neonatal antifungal prophylaxis: non‐inferiority trial. Journal of Clinical Neonatology 2013;2(2):88‐92. [PUBMED: 24049751] - PMC - PubMed
Ozturk 2006 {published data only}
    1. Ozturk MA, Gunes T, Koklu E, Cetin N, Koc N. Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive Care Unit. Mycoses 2006;49(6):484‐92. [PUBMED: 17022766] - PubMed
Sims 1988 {published data only}
    1. Sims ME, Yoo Y, You H, Salminen C, Walther FJ. Prophylactic oral nystatin and fungal infections in very‐low‐birthweight infants. American Journal of Perinatology 1988;5(1):33‐6. [PUBMED: 3276336] - PubMed
Violaris 2010 {published data only}
    1. Violaris K, Carbone T, Bateman D, Olawepo O, Doraiswamy B, LaCorte M. Comparison of fluconazole and nystatin oral suspensions for prophylaxis of systemic fungal infection in very low birthweight infants. American Journal of Perinatology 2010;27(1):73‐8. [PUBMED: 19504425] - PubMed
    1. Violaris K, Doraiswamy B, Olawepo O, Gulrajani‐LaCorte M. Fluconazole versus nystatin prophylaxis for fungal infection in very low birth weight (VLBW) infants. Pediatric Research. 1998; Vol. 44:254A.
Wainer 1992 {published data only}
    1. Wainer S, Cooper PA, Funk E, Bental RY, Sandler DA, Patel J. Prophylactic miconazole oral gel for the prevention of neonatal fungal rectal colonization and systemic infection. Pediatric Infectious Disease Journal 1992;11(9):713‐6. [PUBMED: 1448310] - PubMed

References to studies excluded from this review

Damjanovic 1993 {published data only}
    1. Damjanovic V, Connolly CM, Saene HK, Cooke RW, Corkill JE, Belkum A, et al. Selective decontamination with nystatin for control of a Candida outbreak in a neonatal intensive care unit. Journal of Hospital Infection 1993;24(4):245‐59. [PUBMED: 8104984] - PubMed
Demirel 2013 {published data only}
    1. Demirel G, Celik IH, Erdeve O, Saygan S, Dilmen U, Canpolat FE. Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal colonization and invasive fungal infection in premature infants. European Journal of Paediatrics 2013;172(10):1321‐6. [PUBMED: 23703468] - PubMed
Harris 1960 {published data only}
    1. Harris LJ. Further observations on a simple procedure to eliminate thrush from hospital nurseries. American Journal of Obstetrics and Gynecology 1960;80:30‐1. [PUBMED: 14399978] - PubMed
Herruzo‐Cabrera 1994 {published data only}
    1. Herruzo‐Cabrera R, Garcia Gonzalez JI, Garcia‐Magan P, Rey‐Calero J. Nosocomial infection in a neonatal intensive care unit and its prevention with selective intestinal decolonization. A multivariant evaluation of infection reduction. European Journal of Epidemiology 1994;10(5):573‐80. [PUBMED: 7859857] - PubMed
Oncel 2015 {published data only}
    1. Oncel MY, Arayici S, Sari FN, Simsek GK, Yurttutan S, Erdeve O, et al. Comparison of Lactobacillus reuteri and nystatin prophylaxis on Candida colonization and infection in very low birth weight infants. The Journal of Maternal‐Fetal & Neonatal Medicine 2015;28:1790‐4. [PUBMED: 25245226] - PubMed

Additional references

Adams‐Chapman 2013
    1. Adams‐Chapman I, Bann CM, Das A, Goldberg RN, Stoll BJ, Walsh MC. Neurodevelopmental outcome of extremely low birth weight infants with Candida infection. The Journal of Pediatrics 2013;163(4):961‐7. [PUBMED: 23726546] - PMC - PubMed
Aliaga 2014
    1. Aliaga S, Clark RH, Laughon M, Walsh TJ, Hope WW, Benjamin DK, et al. Changes in the incidence of candidiasis in neonatal intensive care units. Pediatrics 2014;133(2):236‐42. [PUBMED: 24446441] - PMC - PubMed
Ascher 2012
    1. Ascher SB, Smith PB, Watt K, Benjamin DK, Cohen‐Wolkowiez M, Clark RH, et al. Antifungal therapy and outcomes in infants with invasive Candida infections. Pediatric Infectious Disease Journal 2012;31(5):439‐43. [PUBMED: 22189522] - PMC - PubMed
Austin 2007
    1. Clerihew L, Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD003850.pub3] - DOI - PubMed
Barton 2014
    1. Barton M, O'Brien K, Robinson JL, Davies DH, Simpson K, Asztalos E, et al. Invasive candidiasis in low birth weight preterm infants: risk factors, clinical course and outcome in a prospective multicenter study of cases and their matched controls. BMC Infectious Diseases 2014;14:327. [PUBMED: 24924877] - PMC - PubMed
Benjamin 2003
    1. Benjamin DK Jr, Poole C, Steibach WJ, Rowen JL, Walsh TJ. Neonatal candidemia and end‐organ damage: a critical appraisal of the literature using meta‐analytic techniques. Pediatrics 2003;112(3 Pt 1):634‐40. [PUBMED: 12949295] - PubMed
Benjamin 2006
    1. Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, et al. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 2006;117(1):84‐92. [PUBMED: 16396864] - PubMed
Brecht 2009
    1. Brecht M, Clerihew L, McGuire W. Prevention and treatment of invasive fungal infection in very low birthweight infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2009;94(1):F65‐9. [PUBMED: 18838467] - PubMed
Brion 2007
    1. Brion LP, Uko SE, Goldman DL. Risk of resistance associated with fluconazole prophylaxis: systematic review. Journal of Infection 2007;54(6):521‐9. [PUBMED: 17239952] - PubMed
Burwell 2006
    1. Burwell LA, Kaufman D, Blakely J, Stoll BJ, Fridkin SK. Antifungal prophylaxis to prevent neonatal candidiasis: a survey of perinatal physician practices. Pediatrics 2006;118(4):e1019‐26. [PUBMED: 16982807] - PubMed
Clerihew 2006
    1. Clerihew L, Lamagni TL, Brocklehurst P, McGuire W. Invasive fungal infection in very low birthweight infants: national prospective surveillance study. Archives of Disease in Childhood. Fetal and Neonatal Edition 2006;91(3):F188‐92. [PUBMED: 16332924] - PMC - PubMed
Clerihew 2008
    1. Clerihew L, McGuire W. Antifungal prophylaxis for very low birthweight infants: UK national survey. Archives of Disease in Childhood Fetal and Neonatal Edition 2008;93(3):F238‐9. - PubMed
Cotten 2006
    1. Cotten CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin DK Jr, National Institute for Child Health and Human Development Neonatal Research Network. The association of third‐generation cephalosporin use and invasive candidiasis in extremely low birth‐weight infants. Pediatrics 2006;118(2):717‐22. [PUBMED: 16882828] - PubMed
Ernst 1983
    1. Ernst JA, Williams JM, Glick MR, Lemons JA. Osmolality of substances used in the intensive care nursery. Pediatrics 1983;72(3):347‐52. [PUBMED: 6889039] - PubMed
Faix 1989
    1. Faix RG, Kovarik SM, Shaw TR, Johnson RV. Mucocutaneous and invasive candidiasis among very low birth weight (<1,500 grams) infants in intensive care nurseries: a prospective study. Pediatrics 1989;83(1):101‐7. [PUBMED: 2909957] - PubMed
Frattarelli 2004
    1. Frattarelli DA, Reed MD, Giacoia GP, Aranda JV. Antifungals in systemic neonatal candidiasis. Drugs 2004;64(9):949‐68. [PUBMED: 15101785] - PubMed
Friedman 2000
    1. Friedman S, Richardson SE, Jacobs SE, O'Brien K. Systemic Candida infection in extremely low birth weight infants: short term morbidity and long term neurodevelopmental outcome. Pediatric Infectious Disease Journal 2000;19(6):499‐504. [PUBMED: 10877162] - PubMed
Ganesan 2008
    1. Ganesan K, Harigopal S, Neal T, Yoxall CW. Prophylactic oral nystatin for preterm babies under 33 weeks' gestation decreases fungal colonisation and invasive fungaemia. Archives of Disease in Childhood. Fetal and Neonatal Edition 2009;94(4):F275‐8. [PUBMED: 19036756] - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Horbar 2002
    1. Horbar JD, Badger GJ, Carpenter JH, Fanaroff AA, Kilpatrick S, LaCorte M, et al. Members of the Vermont Oxford Network. Trends in mortality and morbidity for very low birth weight infants, 1991–1999. Pediatrics 2002;110(1 Pt 1):143‐51. [PUBMED: 12093960] - PubMed
Howell 2009
    1. Howell AJ, Isaacs D, Halliday R, Australasian Study Group for Neonatal Infections. Oral nystatin prophylaxis and neonatal fungal infections. Archives of Disease in Childhood. Fetal and Neonatal Edition 2009;94(6):F429‐33. [PUBMED: 19321509] - PubMed
Huang 1998
    1. Huang YC, Li CC, Lin TY, Lien RI, Chou YH, Wu JL, et al. Association of fungal colonization and invasive disease in very low birth weight infants. Pediatric Infectious Disease Journal 1998;17(9):819‐22. [PUBMED: 9779769] - PubMed
Isaacs 2008
    1. Isaacs D. Fungal prophylaxis in very low birth weight neonates: nystatin, fluconazole or nothing?. Current Opinion in Infectious Diseases 2008;21(3):246‐50. [PUBMED: 18448968] - PubMed
Kaguelidou 2012
    1. Kaguelidou F, Pandolfini C, Manzoni P, Choonara I, Bonati M, Jacqz‐Aigrain E. European survey on the use of prophylactic fluconazole in neonatal intensive care units. European Journal of Pediatrics 2012;171(3):439‐45. [PUBMED: 21912893] - PMC - PubMed
Karlowicz 2002
    1. Karlowicz MG, Rowen JL, Barnes‐Eley ML, Burke BL, Lawson ML, Bendel CM, et al. The role of birth weight and gestational age in distinguishing extremely low birth weight infants at high risk of developing candidemia from infants at low risk: a multicenter study. Pediatric Research 2002;51:301A.
Kossoff 1998
    1. Kossoff EH, Buescher ES, Karlowicz MG. Candidemia in a neonatal intensive care unit: trends during fifteen years and clinical features of 111 cases. Pediatric Infectious Disease Journal 1998;17(6):504‐8. [PUBMED: 9655543] - PubMed
Lee 1998
    1. Lee BE, Cheung PY, Robinson JL, Evanochko C, Robertson CM. Comparative study of mortality and morbidity in premature infants (birth weight < 1,250g) with candidemia or candidal meningitis. Clinical Infectious Diseases 1998;27(3):559‐65. [PUBMED: 9770157] - PubMed
Makhoul 2002
    1. Makhoul IR, Sujov P, Smolkin T, Lusky A, Reichman B. Epidemiological, clinical, and microbiological characteristics of late‐onset sepsis among very low birth weight infants in Israel: a national survey. Pediatrics 2002;109(1):34‐9. - PubMed
Manzoni 2006
    1. Manzoni P, Farina D, Leonessa M, d'Oulx EA, Galletto P, Mostert M, et al. Risk factors for progression to invasive fungal infection in preterm neonates with fungal colonization. Pediatrics 2006;118(6):2359‐64. - PubMed
O'Grady 2008
    1. O'Grady MJ, Dempsey EM. Antifungal prophylaxis for the prevention of neonatal candidiasis?. Acta Paediatrica 2008;97(4):430‐3. [PUBMED: 18363952] - PubMed
Oeser 2013
    1. Oeser C, Lamagni T, Heath PT, Sharland M, Ladhani S. The epidemiology of neonatal and pediatric candidemia in England and Wales, 2000‐2009. The Pediatric Infectious Disease Journal 2013;32:23‐6. [PUBMED: 23241987] - PubMed
Oeser 2014
    1. Oeser C, Vergnano S, Naidoo R, Anthony M, Chang J, Chow P, et al. Neonatal invasive fungal infection in England 2004‐2010. Clinical Microbiology and Infection 2014;20:936‐41. [PUBMED: 24479862] - PubMed
Pappu‐Katikaneni 1990
    1. Pappu‐Katikaneni LD, Rao KP, Banister E. Gastrointestinal colonization with yeast species and Candida septicemia in very low birth weight infants. Mycoses 1990;33(1):20‐3. [PUBMED: 2342516] - PubMed
Radmacher 2012
    1. Radmacher PG, Adamkin MD, Lewis ST, Adamkin DH. Milk as a vehicle for oral medications: hidden osmoles. Journal of Perinatology 2012;32(3):227‐9. [PUBMED: 21701446] - PubMed
Robinson 2009
    1. Robinson JL, Davies HD, Barton M, O'Brien K, Simpson K, Asztalos E, et al. Characteristics and outcome of infants with candiduria in neonatal intensive care ‐ a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study. BMC Infectious Diseases 2009;9:183. [PUBMED: 19930662] - PMC - PubMed
Rowen 1994
    1. Rowen JL, Rench MA, Kozinetz CA, Adams JM, Baker CJ. Endotracheal colonization with candida enhances risk of systemic candidiasis in very low birth weight neonates. Journal of Pediatrics 1994;124(5 Pt 1):789‐94. [PUBMED: 8176570] - PubMed
Saiman 2000
    1. Saiman L, Ludington E, Pfaller M, Rangel‐Frausto S, Wiblin RT, Dawson J, et al. Risk factors for candidemia in Neonatal Intensive Care Unit patients. The national epidemiology of mycosis survey study group. Pediatric Infectious Disease Journal 2000;19(4):319‐24. [PUBMED: 10783022] - PubMed
Shane 2013
    1. Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis. American Journal of Perinatology 2013;30(2):131‐41. [PUBMED: 23297182] - PubMed
Stoll 2002
    1. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late‐onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002;110(2 Pt 1):285‐91. [PUBMED: 12165580] - PubMed
Vergnano 2011
    1. Vergnano S, Menson E, Kennea N, Embleton N, Russell AB, Watts T, et al. Neonatal infections in England: the NeonIN surveillance network. Archives of Disease in Childhood. Fetal and Neonatal Edition 2011;96(1):F9‐14. [PUBMED: 20876594] - PubMed
Wynn 2012
    1. Wynn JL, Tan S, Gantz MG, Das A, Goldberg RN, Adams‐Chapman I, et al. Outcomes following candiduria in extremely low birth weight infants. Clinical Infectious Diseases 2012;54(3):331‐9. [PUBMED: 22144537] - PMC - PubMed

References to other published versions of this review

Austin 2004
    1. Austin NC, Darlow B. Prophylactic oral antifungal agents to prevent systemic candida infection in preterm infants. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD003478.pub2] - DOI - PubMed
Austin 2009
    1. Austin N, Darlow BA, McGuire W. Prophylactic oral/topical non‐absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD003478.pub3] - DOI - PubMed
Austin 2013
    1. Austin N, Darlow BA, McGuire W. Prophylactic oral/topical non‐absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants. Cochrane Database of Systematic Reviews 2013, Issue 3. [DOI: 10.1002/14651858.CD003478.pub4] - DOI - PubMed

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