Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study

Author:

Cook Aislinn1ORCID,Ferreras-Antolin Laura12ORCID,Adhisivam Bethou3,Ballot Daynia45,Berkley James A678,Bernaschi Paola9,Carvalheiro Cristina G1011,Chaikittisuk Napaporn12,Chen Yunsheng13,Chibabhai Vindana1415,Chitkara Shweta16,Chiurchiu Sara17,Chorafa Elisavet18,Dien Tran Minh1920,Dramowski Angela21,de Matos Samantha Faria22,Feng Jinxing23,Jarovsky Daniel22ORCID,Kaur Ravinder16,Khamjakkaew Warunee24,Laoyookhong Premsak12,Machanja Edwin25,Mussi-Pinhata Marisa M1011,Namiiro Flavia26,Natraj Gita27,Naziat Hakka28,Ngoc Hoang Thi Bich29,Ondongo-Ezhet Claude30,Preedisripipat Kanchana31,Rahman Hafizur28,Riddell Amy1,Roilides Emmanuel18,Russell Neal1,Sastry Apurba S32,Tasimwa Hannington Baluku33,Tongzhen Ji3435,Wadula Jeannette3637,Wang Yajuan3839,Whitelaw Andrew4041,Wu Dan38,Yadav Varsha27,Yang Gao343637,Stohr Wolfgang42,Bielicki Julia Anna1,Ellis Sally43,Warris Adilia2,Heath Paul T1,Sharland Michael1

Affiliation:

1. Centre for Neonatal and Paediatric Infection, St. George's University of London , London , UK

2. MRC Centre for Medical Mycology, University of Exeter , Exeter , UK

3. Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) , Pondicherry , India

4. School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand , Johannesburg , South Africa

5. Charlotte Maxeke Johannesburg Academic Hospital , Johannesburg, South Africa

6. Clinical Research Department , KEMRI-Wellcome Trust Research Programme, Kilifi , Kenya

7. Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford , Oxford , UK

8. The Childhood Acute Illness & Nutrition (CHAIN) Network , Nairobi , Kenya

9. Microbiology Unit, Bambino Gesù Children's Hospital , Rome , Italy

10. Department of Pediatrics, Ribeirão Preto Medical School, University , São Paulo, Brazil

11. of São Paulo , São Paulo, Brazil

12. Queen Sirikit National Institute of Child Health , Bangkok , Thailand

13. Clinical Laboratory, Shenzhen Children's Hospital , Shenzhen , China

14. Department of Clinical Microbiology & Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of Witwatersrand , Johannesburg , South Africa

15. NHLS Microbiology Laboratory, Charlotte Maxeke Johannesburg Academic Hospital , Johannesburg , South Africa

16. Lady Hardinge Medical College & Associated SSK & KSC Hospitals , New Delhi , India

17. Academic Hospital Paediatric Department, Bambino Gesù Children's Hospital , Rome , Italy

18. Infectious Diseases Unit, 3rd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University and Hippokration General Hospital , Thessaloniki , Greece

19. Vice Director Vietnam National Children's Hospital , Hanoi , Vietnam

20. Department of Surgery, Vietnam National Children's Hospital , Hanoi , Vietnam

21. Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town, South Africa

22. Santa Casa de São Paulo , Sao Paulo , Brazil

23. Department of Neonatology, Shenzhen Children's Hospital , Shenzhen , China

24. PHPT/IRD-MIVEGEC, Chiang Mai University , Chiang Rai , Thailand

25. Department of Microbiology , KEMRI-Wellcome Trust Research Programme, Kilifi , Kenya

26. Mulago Specialised Women and Neonatal Hospital , Kampala , Uganda

27. Seth G. S. Medical College & KEM Hospital , Mumbai , India

28. Child Health Research Foundation , Dhaka , Bangladesh

29. Department of Microbiology, Vietnam National Children's Hospital , Hanoi , Vietnam

30. School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg , South Africa

31. Chiangrai Prachanukroh Hospital , Chiang Rai , Thailand

32. Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER) , Pondicherry , India

33. Department of Mircobiology, College of Health Sciences, Makerere University , Kampala , Uganda

34. Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing , China

35. Beijing Maternal and Child Health Care Hospital , Beijing , China

36. National Health Laboratory Services, School of Pathology, Faculty of Health Sciences, University

37. of the Witwatersrand, Johannesburg, South Africa

38. Department of Neonatology, Children's Hospital, Capital Institute of Pediatrics, 2# Yabao Road , Chaoyang District, Beijing , China

39. Department of Neonatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University , Beijing , China

40. Division of Medical Microbiology, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town, South Africa

41. National Health Laboratory Service, Tygerberg Hospital , Cape Town , South Africa

42. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London , London , UK

43. Global Antibiotic Research & Development Partnership (GARDP) , Geneva , Switzerland

Abstract

AbstractNeonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018–February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28–34), and median birth weight was 1270 gr (interquartile range [IQR]: 990–1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Funder

University of Exeter

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,General Medicine

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