Fluconazole prophylaxis in high-risk, very low birth weight infants

고위험 극소저체중 출생아에서 fluconazole 예방요법

  • Kim, Soo Young (Department of Pediatrics, School of Medicine, Chonnam National University) ;
  • Lee, Soon Joo (Department of Pediatrics, School of Medicine, Chonnam National University) ;
  • Kim, Mi Jeong (Department of Pediatrics, School of Medicine, Chonnam National University) ;
  • Song, Eun Song (Department of Pediatrics, School of Medicine, Chonnam National University) ;
  • Choi, Young Youn (Department of Pediatrics, School of Medicine, Chonnam National University)
  • 김수영 (전남대학교 의과대학 소아과학교실) ;
  • 이순주 (전남대학교 의과대학 소아과학교실) ;
  • 김미정 (전남대학교 의과대학 소아과학교실) ;
  • 송은송 (전남대학교 의과대학 소아과학교실) ;
  • 최영륜 (전남대학교 의과대학 소아과학교실)
  • Received : 2007.04.18
  • Accepted : 2007.06.11
  • Published : 2007.07.15

Abstract

Purpose : Fluconazole prophylaxis for very low birth weight (VLBW) infants has been shown to reduce invasive fungal infection and its mortality. This study aims to evaluate the effect of fluconazole prophylaxis in VLBW infants on the incidence and mortality of fungal infection. Methods : VLBW infants with endotracheal intubation and central vascular access admitted to the Neonatal Intensive Care Unit (NICU) at Chonnam University Hospital were enrolled. Twenty eight infants of 7-month baseline period from January to July 2005 ('non-fluconazole group') were compared with 29 infants of a 7-month fluconazole period from January to July 2006 ('fluconazole group'). Results : Gestational age, birth weight, sex, mode of delivery, frequency of twin pregnancy, chorioamnionitis, antenatal steroid and rupture of membranes were similar between the fluconazole and non-fluconazole groups. The rate of extremely low birth weight (ELBW) infants, frequency and duration of prophylactic antibiotics, total parenteral nutrition and umbilical catheters, duration of intralipid, mechanical ventilation and nasal continuous positive airway pressure (CPAP) were also not significant. However, frequency of percutaneous central venous catheterization (PCVC) and intralipid administration, and duration of PCVC were significant between the two groups. The overall incidence and mortality of fungal infection were not different between the two groups. Although the Malassezia infection was increased in the fluconazole group (P<0.05), candida was significantly decreased compared to the non-fluconazole group (P<0.05). Conclusion : Fluconazole prophylaxis in high risk VLBW infants decreased the candida infection significantly. Antifungal prophylaxis is recommended in terms of cost effectiveness, but further study is needed to clarify the reason for the increase of Malassezia infection.

목 적 : 면역력이 약한 미숙아나 저체중 출생아에 여러 가지 침습적 조작으로 인한 항생제 사용이 진균 감염, 특히 칸디다 감염의 위험을 증가시킨다. 이를 감소시키기 위한 방법으로 fluconazole 예방요법이 칸디다 감염율과 사망률을 감소시켰다는 보고가 있다. 본 연구는 1,500 g 미만의 극소저체중 출생아들에 대한 예방적 항진균제 사용이 칸디다 감염의 발생을 감소시키는데 효과적인지 알아보고자 하였다. 방 법 : 전남대학병원 신생아중환자실에 입원한 1,500 g 미만의 극소저체중 출생아 중 기관내 삽관이나 제대 동정맥 또는 경피적 중심정맥 삽입술을 받은 환아로, 예방적으로 항진균제를 사용하지 않았던 2005년 1월 1일부터 2005년 7월 31일까지 7개월간의 환아를 'fluconazole 비사용군'으로, 사용하였던 2006년 1월 1일부터 2006년 7월 31일까지 7개월간의 환아를 'fluconazole 사용군'으로 하였다. 사용군 29명, 비사용군 28명을 대상으로 진균 감염의 위험인자로 알려진 임상특성과 칸디다 감염증의 발생빈도, 사망률 및 fluconazole의 약물 부작용을 관찰하였다. Fluconazole은 생후 첫 3일에 시작하여 4주간 예방적으로 투여하였으며 시행 첫 1주일은 체중(kg)당 3 mg을 3일 간격으로, 그 다음 주부터는 격일로 투여하였다. 결 과 : 두 군 사이에 재태주령, 출생체중, 성별, 쌍생아, 분만방식에 차이는 없었다. 산과적 인자인 장기 조기 양막파수, 융모양막염 및 산전 스테로이드 사용 빈도에 유의한 차이는 없었다. 신생아 칸디다 감염증의 위험인자로 알려진 1,000 g 미만 초극소저체중 출생아 빈도와 예방적 항생제 사용, 총정맥내 영양요법, 제대동정맥 삽입술 빈도와 유지기간, 지방유제 투여기간 및 기관내 삽관과 지속적 양압환기 사용기간에 두 군간 차이는 없었으나, 비사용군에 비해 사용군이 경피적 중심정맥 삽입술과 지방유제 사용빈도가 높았고 경피적 중심정맥관 유지기간이 길었다. Fluconazole 사용군과 비사용군 간에 진균감염의 빈도와 사망률에 유의한 차이는 없었다. 사용군에서 Malassezia 진균혈증이 5명 발생하였지만 칸디다 감염은 1명도 발생하지 않아 비사용군 5명(칸디다혈증 3명, 침습성 칸디다증 2명)에 비해 유의하게 감소하였다(P<0.05). 결 론 : 극소저체중 출생아에서 fluconazole의 예방적 투여가 칸디다 감염의 발생빈도를 유의하게 감소시키는 것으로 보아 비용-효과 면에서 항진균제의 예방적 투여가 고려될 수 있겠으나, Malassezia 진균혈증의 증가 원인에 대해서도 추가적인 연구가 필요할 것으로 사료된다.

Keywords

References

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