알부민이 첨가된 시험관내 약역학 감염모델을 이용한 폐렴알균 치료에서 Ceftriaxone 일일 1회 요법
Once-daily Dosing of Ceftriaxone against Streptococcus pneumoniae Isolates in an In Vitro Pharmacodynamic Infection Model supplemented with Albumin
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배 경 : Penicillin 내성 폐렴알균이 증가하는 지역에서 대안 중의 하나로 사용되는 ceftriaxone (CTR)의 적절한 용법, 용량을 파악하는 것이 중요하다. 본 연구는 임상에서 분리된 폐렴알균을 대상으로 시험관내 약역학 감염모델을 이용하여 알부민이 첨가된 경우와 첨가되지 않은 경우 CTR의 일일 1회 요법의 효과를 비교해 보고자 하였다. 재료 및 방법 : Penicillin 감수성(SM24), 중간내성(SM47), 내성(SM60)주를 대상으로 2-구획 시험관내 약역학 감염모델을 적용하였다. CTR 주입은 2 g씩 24시간마다로 사람의 약동학을 모의하였다. 알부민은 모델에서 4 g/ dL가 유지되도록 하였다. 살균효과는 0, 2, 4, 6, 24, 30, 48시간째 집락수 변화로 측정하였다. 결 과 : 모든 균주에서 알부민이 첨가되지 않은 경우 6시간 이내에 살균력이 관찰되었다. 최저억제농도 및 알부민 첨가유무에 관계없이 3주 모두 24시간째 살균력이 관찰되었고, 48시간째는 모두 측정한계 이하의 집락수로 감소하였다. 전 실험과정에서 CTR에 대한 내성주는 출현하지 않았다. 결 론 : CTR의 일일 1회 요법은 알부민이 첨가되었을 때, 감수성, 중간내성, 내성주 모두에서 살균력 발현이 지연되었으나 최종효과는 알부민이 없을 때와 다르지 않았다. 앞으로 알부민 결합효과와 관련된 기초적인 추가 연구가 필요할 것으로 생각된다
Abstract
Background : During the era of increasing penicillin resistant Streptococcus pneumoniae, it is important to have knowledge about adequate dosage and dosing interval of ceftriaxone (CTR). We examined efficacies of once-daily CTR and compared results in an in vitro pharmacodynamic infection model (IVPDIM) supplemented with albumin and those without albumin. Methods : Using three clinically isolated S. pneumoniae that were susceptible (SM24), intermediate (SM47) and resistant (SM60) against CTR, we utilized a two-compartment IVPDIM. CTR 2 g was administered intravenously every 24 h. Human albumin was added with concentration of 4 g/dL. Samples were removed at multiple time points over a 48-h period to determine the colony counts. Results : In SM24 and SM60, bactericidal effects were observed within 6 hours in groups without albumin. The number of colonies during 1st 6 hours were more decreased in albumin-free groups than in albumin-supplemented groups (P<0.05). In SM47, similar results were found during 1st 6 hours (P=0.03). But, regrowth was observed in albumin supplemented group at 30 h. Irrespective of results of minimal inhibitory concentrations and albumin supplementation, bactericidal effects were shown at 24 h in all 3 strains. All groups were decreased below the detection limit at 48 h. Development of resistance was not detected throughout the entire study period in either strain. Conclusions : Although extents of killing in albumin supplemented broth of once-daily CTR dosing were delayed in all 3 strains compared with those of albumin free broth, final efficacies were not different between the two groups.
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