早产儿侵袭性真菌感染药物预防策略的研究进展

黄方俊; 熊涛; 唐军

doi:10.7499/j.issn.1008-8830.2204158

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中国当代儿科杂志 ›› 2022, Vol. 24 ›› Issue (10) : 1171-1177. DOI: 10.7499/j.issn.1008-8830.2204158

综述

早产儿侵袭性真菌感染药物预防策略的研究进展

黄方俊¹, 熊涛^1,2, 唐军^1,2

作者信息 +

Recent research on pharmacological prevention strategies for invasive fungal infection in preterm infants

HUANG Fang-Jun, XIONG Tao, TANG Jun

Author information +

文章历史 +

摘要

新生儿重症监护病房中早产儿的侵袭性真菌感染（invasive fungal infection，IFI）发生率较高，且早期临床诊断困难，一旦发生，病情重，疗程长，花费高，病死率较高，预后差。因此预防IFI尤为重要。目前临床常选氟康唑作为预防早产儿IFI的一线药物，但具体剂量、疗程尚不统一，使用对象及预防效果也存在争议。该文对近年来新生儿重症监护病房中药物预防早产儿IFI的研究进展进行综述，供临床医生参考。

Abstract

There is a relatively high incidence rate of invasive fungal infection (IFI) in preterm infants admitted to the neonatal intensive care unit (NICU), and early diagnosis of IFI is difficult in clinical practice. The patients developing IFI tend to have severe conditions, a long course of treatment, high hospital costs, high mortality, and poor prognosis, and therefore, the prevention of IFI is of particular importance. At present, fluconazole is often used as the first-line drug for the prevention of IFI in preterm infants, but no consensus has been reached on the specific dose and course of treatment, and there are still controversies over the targeted population and prophylactic effect. This article reviews the recent research on the pharmacological prevention strategies for IFI in preterm infants in the NICU, so as to provide a reference for clinicians.

导出引用

黄方俊, 熊涛, 唐军. 早产儿侵袭性真菌感染药物预防策略的研究进展[J]. 中国当代儿科杂志. 2022, 24(10): 1171-1177 https://doi.org/10.7499/j.issn.1008-8830.2204158

HUANG Fang-Jun, XIONG Tao, TANG Jun. Recent research on pharmacological prevention strategies for invasive fungal infection in preterm infants[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(10): 1171-1177 https://doi.org/10.7499/j.issn.1008-8830.2204158

参考文献

1 Brady MT. Health care-associated infections in the neonatal intensive care unit[J]. Am J Infect Control, 2005, 33(5): 268-275. PMID: 15947743. PMCID: PMC7119124. DOI: 10.1016/j.ajic.2004.11.006.
2 Zhang Z, Cao Y, Li Y, et al. Risk factors and biofilm formation analyses of hospital-acquired infection of Candida pelliculosa in a neonatal intensive care unit[J]. BMC Infect Dis, 2021, 21(1): 620. PMID: 34187390. PMCID: PMC8244135. DOI: 10.1186/s12879-021-06295-1.
3 Lona-Reyes JC, Gómez-Ruiz LM, Cordero-Zamora A, et al. Incidence and factors associated with invasive candidiasis in a neonatal intensive care unit in Mexico[J]. An Pediatr (Engl Ed), 2021. Epub ahead of print. PMID: 34334329. DOI: 10.1016/j.anpedi.2021.07.001.
4 Manzoni P, Farina D, Leonessa M, et al. Risk factors for progression to invasive fungal infection in preterm neonates with fungal colonization[J]. Pediatrics, 2006, 118(6): 2359-2364. PMID: 17142519. DOI: 10.1542/peds.2006-1311.
5 Piqueras A, Ganapathi L, Carpenter JF, et al. Trends in pediatric candidemia: epidemiology, anti-fungal susceptibility, and patient characteristics in a children's hospital[J]. J Fungi (Basel), 2021, 7(2): 78. PMID: 33499285. PMCID: PMC7911199. DOI: 10.3390/jof7020078.
6 Lona-Reyes JC, Gómez-Ruiz LM, Cordero-Zamora A, et al. Bloodstream infections with Candida glabrata in a neonatal intensive care unit that uses prophylaxis with fluconazole[J]. Rev Iberoam Micol, 2020, 37(3-4): 100-103. PMID: 33229296. DOI: 10.1016/j.riam.2020.06.002.
7 Weimer KED, Smith PB, Puia-Dumitrescu M, et al. Invasive fungal infections in neonates: a review[J]. Pediatr Res, 2022, 91(2): 404-412. PMID: 34880444. DOI: 10.1038/s41390-021-01842-7.
8 Benedict K, Roy M, Kabbani S, et al. Neonatal and pediatric candidemia: results from population-based active laboratory surveillance in four US locations, 2009-2015[J]. J Pediatric Infect Dis Soc, 2018, 7(3): e78-e85. PMID: 29522195. DOI: 10.1093/jpids/piy009.
9 Benjamin DK, Stoll BJ, Fanaroff AA, et al. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months[J]. Pediatrics, 2006, 117(1): 84-92. PMID: 16396864. DOI: 10.1542/peds.2004-2292.
10 Engbers AGJ, Flint RB, Voeller S, et al. Optimisation of fluconazole therapy for the treatment of invasive candidiasis in preterm infants[J]. Arch Dis Child, 2022, 107(4): 400-406. PMID: 35074829. DOI: 10.1136/archdischild-2021-322560.
11 Ramos JT, Romero CA, Belda S, et al. Clinical practice update of antifungal prophylaxis in immunocompromised children[J]. Rev Esp Quimioter, 2019, 32(5): 410-425. PMID: 31507152. PMCID: PMC6790888.
12 Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America[J]. Clin Infect Dis, 2016, 62(4): e1-e50. PMID: 26679628. PMCID: PMC4725385. DOI: 10.1093/cid/civ933.
13 Wang XL, Ma Y, Wang SH, et al. A meta-analysis of fluconazole for the prevention of invasive fungal infection in preterm infants[J]. Am J Transl Res, 2021, 13(2): 434-447. PMID: 33594302. PMCID: PMC7868852.
14 Autmizguine J, Smith PB, Prather K, et al. Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants[J]. J Antimicrob Chemother, 2018, 73(12): 3482-3487. PMID: 30247579. PMCID: PMC6927883. DOI: 10.1093/jac/dky353.
15 Silva-Rios J, Camargos P, Correa L, et al. Prophylactic regimens with fluconazole for candidiasis in neonates under 1,500 g: a retrospective chart review of two cohorts[J]. J Neonatal Perinatal Med, 2019, 12(1): 29-36. PMID: 30958318. DOI: 10.3233/NPM-17121.
16 Luparia M, Landi F, Mesini A, et al. Fungal ecology in a tertiary neonatal intensive care unit after 16 years of routine fluconazole prophylaxis: no emergence of native fluconazole-resistant strains[J]. Am J Perinatol, 2019, 36(S 02): S126-S133. PMID: 31238373. DOI: 10.1055/s-0039-1691808.
17 邓庆先, 林梅芳. 口服氟康唑预防极低出生体质量早产儿真菌感染的临床意义[J]. 中国妇幼保健, 2020, 35(23): 4519-4522. DOI: 10.19829/j.zgfybj.issn.1001-4411.2020.23.038.
18 Zhang D, Xie D, He N, et al. Prophylactic use of fluconazole in very premature infants[J]. Front Pediatr, 2021, 9: 726769. PMID: 34660487. PMCID: PMC8517516. DOI: 10.3389/fped.2021.726769.
19 Benjamin DK, Hudak ML, Duara S, et al. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial[J]. JAMA, 2014, 311(17): 1742-1749. PMID: 24794367. PMCID: PMC4110724. DOI: 10.1001/jama.2014.2624.
20 Hope WW, Castagnola E, Groll AH, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp[J]. Clin Microbiol Infect, 2012, 18 Suppl 7: 38-52. PMID: 23137136. DOI: 10.1111/1469-0691.12040.
21 Robati Anaraki M, Nouri-Vaskeh M, Abdoli Oskoei S. Fluconazole prophylaxis against invasive candidiasis in very low and extremely low birth weight preterm neonates: a systematic review and meta-analysis[J]. Clin Exp Pediatr, 2021, 64(4): 172-179. PMID: 32683818. PMCID: PMC8024115. DOI: 10.3345/cep.2019.01431.
22 Leonart LP, Tonin FS, Ferreira VL, et al. Fluconazole doses used for prophylaxis of invasive fungal infection in neonatal intensive care units: a network meta-analysis[J]. J Pediatr, 2017, 185: 129-135.e6. PMID: 28285752. DOI: 10.1016/j.jpeds.2017.02.039.
23 Kaufman DA, Morris A, Gurka MJ, et al. Fluconazole prophylaxis in preterm infants: a multicenter case-controlled analysis of efficacy and safety[J]. Early Hum Dev, 2014, 90 Suppl 1: S87-S90. PMID: 24709470. DOI: 10.1016/S0378-3782(14)70026-X.
24 White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance[J]. Clin Microbiol Rev, 1998, 11(2): 382-402. PMID: 9564569. PMCID: PMC106838. DOI: 10.1128/CMR.11.2.382.
25 Magobo RE, Naicker SD, Wadula J, et al. Detection of neonatal unit clusters of Candida parapsilosis fungaemia by microsatellite genotyping: results from laboratory-based sentinel surveillance, South Africa, 2009-2010[J]. Mycoses, 2017, 60(5): 320-327. PMID: 28101934. DOI: 10.1111/myc.12596.
26 Nazir A, Masoodi T. Spectrum of candidal species isolated from neonates admitted in an intensive care unit of teaching hospital of Kashmir, North India[J]. J Lab Physicians, 2018, 10(3): 255-259. PMID: 30078958. PMCID: PMC6052818. DOI: 10.4103/JLP.JLP_1_18.
27 Chen IL, Chiu NC, Chi H, et al. Changing of bloodstream infections in a medical center neonatal intensive care unit[J]. J Microbiol Immunol Infect, 2017, 50(4): 514-520. PMID: 26440920. DOI: 10.1016/j.jmii.2015.08.023.
28 Chen IT, Chen CC, Huang HC, et al. Malassezia furfur emergence and candidemia trends in a neonatal intensive care unit during 10 years: the experience of fluconazole prophylaxis in a single hospital[J]. Adv Neonatal Care, 2020, 20(1): E3-E8. PMID: 31306235. PMCID: PMC7004458. DOI: 10.1097/ANC.0000000000000640.
29 Ramya GM, Balakrishnan U, Chandrasekaran A, et al. Candida auris, an emerging pathogen—challenge in the survival of microprimies[J]. Indian J Med Microbiol, 2021, 39(3): 367-369. PMID: 33906749. DOI: 10.1016/j.ijmmb.2021.03.025.
30 Rundjan L, Wahyuningsih R, Oeswadi CA, et al. Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial[J]. BMC Pediatr, 2020, 20(1): 170. PMID: 32303210. PMCID: PMC7164192. DOI: 10.1186/s12887-020-02074-0.
31 Aydemir C, Oguz SS, Dizdar EA, 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[J]. Arch Dis Child Fetal Neonatal Ed, 2011, 96(3): F164-F168. PMID: 20659937. DOI: 10.1136/adc.2009.178996.
32 Ganesan K, Harigopal S, Neal T, et al. Prophylactic oral nystatin for preterm babies under 33 weeks' gestation decreases fungal colonisation and invasive fungaemia[J]. Arch Dis Child Fetal Neonatal Ed, 2009, 94(4): F275-F278. PMID: 19036756. DOI: 10.1136/adc.2008.145359.
33 Bodin MB, Godoy G, Philips JB. Topical nystatin for the prevention of catheter-associated candidiasis in ELBW infants[J]. Adv Neonatal Care, 2015, 15(3): 220-224. PMID: 25938952. DOI: 10.1097/ANC.0000000000000170.
34 Howell A, Isaacs D, Halliday R, et al. Oral nystatin prophylaxis and neonatal fungal infections[J]. Arch Dis Child Fetal Neonatal Ed, 2009, 94(6): F429-F433. PMID: 19321509. DOI: 10.1136/adc.2008.157123.
35 Isaacs D. Fungal prophylaxis in very low birth weight neonates: nystatin, fluconazole or nothing?[J]. Curr Opin Infect Dis, 2008, 21(3): 246-250. PMID: 18448968. DOI: 10.1097/QCO.0b013e3282f8adab.
36 中华医学会儿科学分会, 中华儿科杂志编辑委员会. 儿童侵袭性肺部真菌感染临床实践专家共识(2022版)[J]. 中华儿科杂志, 2022, 60(4): 274-282. PMID: 35385930. DOI: 10.3760/cma.j.cn112140-20220210-00112.
37 Lehrnbecher T, Fisher BT, Phillips B, et al. Clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation recipients[J]. J Clin Oncol, 2020, 38(27): 3205-3216. PMID: 32459599. PMCID: PMC7499615. DOI: 10.1200/JCO.20.00158.
38 Arrieta AC, Shea K, Dhar V, et al. Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: a prospective, randomized, open-label, placebo-controlled pilot study[J]. Clin Ther, 2010, 32(2): 265-271. PMID: 20206784. DOI: 10.1016/j.clinthera.2010.02.016.
39 Chandramati J, Sadanandan L, Kumar A, et al. Neonatal Candida auris infection: management and prevention strategies—a single centre experience[J]. J Paediatr Child Health, 2020, 56(10): 1565-1569. PMID: 32672390. DOI: 10.1111/jpc.15019.
40 Maede Y, Ibara S, Nagasaki H, et al. Micafungin versus fluconazole for prophylaxis against fungal infections in premature infants[J]. Pediatr Int, 2013, 55(6): 727-730. PMID: 23773357. DOI: 10.1111/ped.12157.
41 Leverger G, Timsit JF, Milpied N, et al. Use of micafungin for the prevention and treatment of invasive fungal infections in everyday pediatric care in France: results of the MYRIADE study[J]. Pediatr Infect Dis J, 2019, 38(7): 716-721. PMID: 31192976. DOI: 10.1097/INF.0000000000002353.
42 Demirel G, Celik IH, Erdeve O, et al. Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal colonization and invasive fungal infection in premature infants[J]. Eur J Pediatr, 2013, 172(10): 1321-1326. PMID: 23703468. DOI: 10.1007/s00431-013-2041-4.
43 Manzoni P, Mostert M, Leonessa ML, et al. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study[J]. Clin Infect Dis, 2006, 42(12): 1735-1742. PMID: 16705580. DOI: 10.1086/504324.
44 Romeo MG, Romeo DM, Trovato L, et al. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome[J]. J Perinatol, 2011, 31(1): 63-69. PMID: 20410904. PMCID: PMC3016918. DOI: 10.1038/jp.2010.57.
45 Roy A, Chaudhuri J, Sarkar D, et al. Role of enteric supplementation of probiotics on late-onset sepsis by Candida species in preterm low birth weight neonates: a randomized, double blind, placebo-controlled trial[J]. N Am J Med Sci, 2014, 6(1): 50-57. PMID: 24678479. PMCID: PMC3938875. DOI: 10.4103/1947-2714.125870.
46 Hu HJ, Zhang GQ, Zhang Q, et al. Probiotics prevent Candida colonization and invasive fungal sepsis in preterm neonates: a systematic review and meta-analysis of randomized controlled trials[J]. Pediatr Neonatol, 2017, 58(2): 103-110. PMID: 27793494. DOI: 10.1016/j.pedneo.2016.06.001.
47 Manzoni P, Stolfi I, Messner H, et al. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial[J]. Pediatrics, 2012, 129(1): 116-123. PMID: 22184648. DOI: 10.1542/peds.2011-0279.