抗生物質医薬品は，微生物の発酵生産により得られる天然物であることから，ワクチンなどと同様な生物学的製剤と見なされ，薬事行政上は国家検定の対象となる基準品目として取り扱われてきた。初期の抗生物質の発酵工程，抽出工程，精製工程及び製剤化工程は何れも未熟であったため，患者に投与する製品中に未知の毒性物質，発熱性物質，血圧降下物質などが混入することが懸念され，それらの有害物質の混在を検出するためにマウス，ウサギ，ネコを用いる生物学的な安全性試験が課されていた。

抗生物質医薬品の発展は著しく，作用や薬理学的性状に優れる多数の化学誘導体が臨床に導入されて主流となった結果，従来の生物学的製剤と見なす取り扱いは不合理となり，一般の化学薬品と同様に取り扱うことが適切であると判断された。その結果，抗生物質医薬品の国家検定は廃止され，「日本抗生物質医薬品基準」は「日本薬局方」に統合された。統合に際しては，「日本薬局方」の理念に適合しない動物試験を廃止するか化学的な試験に置き換える必要があり作業が進められた。

本報では，抗生物質医薬品に課されていた各種の生物学的な安全性試験の制定の意義と試験法の変遷及びそれら試験の見直しについて，薬事行政上の対応を含めて調査・解析し，考察を加えた。

A 63-year-old woman visited our hospital complaining of fever and dyspnea. Her inflammatory response was strongly positive, with hyperglycemia, severe hypoxia, a high level of procalcitonin, and an influenza B antigen-positive result. Chest computed tomography (CT) on admission showed multiple nodules with infiltrative shadows in the bilateral lung fields, and gram-positive coccus with phagocytosis by neutrophils was observed in a sputum sample. Although treatments using sulbactam/ampicillin (SBT/ABPC) and azithromycin (AZM) plus peramivir were initiated, the clinical effect was poor due to the delay of administration of linezolid (LZD). Because methicillin-resistant Staphylococcus aureus (MRSA) was isolated from sputum, treatments were changed to LZD plus AZM. Molecular analysis of the MRSA isolate showed as follows: multilocus sequence typing (MLST) 8, staphylococcal cassette chromosome mec (SCCmec) typeIV, spa type t1767, Panton-Valentine leucocidin (PVL)-negative, arginine catabolic mobile element (ACME)-negative, and toxic shock syndrome toxin-1 (TSST)-1-positive. Influenza B and TSST-1 produced by community acquired MRSA (CA-MRSA) may have been involved in the formation of necrotizing pneumonia in this patient. However, she improved following the administration of peramivir and LZD.

Objectives To describe, in detail, the influence of antibiotics on the microflora of children with respiratory syncytial virus (RSV) infection.

Methods Eight hospitalized infants with RSV infection were included in the study. To examine the change in the microflora before and after the use of antibiotics, we simultaneously collected nasopharyngeal and stool swabs from each patient at 3 points; before antibiotics use, during antibiotics use, after use. The use of antibiotics was determined by clinicians. In 6 patients, antibiotics were used, and in 2, they were not. We analyzed the nasopharyngeal and fecal microflora through the clone library method, using amplified fragments of the 16S ribosomal RNA gene with universal primers.

Results With regards to nasopharyngeal microflora, of the 6 patients who were prescribed antibiotics, 4 had pathogenic bacteria including Haemophilus influenzae and Moraxella catarrhalis, on admission, and only 1 patient had M. catarrhalis 3–5 days after admission. However, in 3 patients, M. catarrhalis was the dominant bacterium, 1–2 weeks after hospital discharge. Among the patients who were not prescribed antibiotics, the representative pathogens of childhood pneumonia were not observed in any of the patients 1–2 weeks after hospital discharge, despite them having those pathogens on admission or 3–5 days after. With regards to fecal microflora, the number of bacterial species decreased after antibiotics use, except in 1 patient. One to 2 weeks after hospital discharge, the number of bacterial species was lower than that observed on admission, in all the cases in which antibiotics were used.

Conclusions The number of bacterial species both in the nasopharyngeal and fecal samples decreased after antibiotic use. The change in the dominant bacteria of the nasopharynx may be different between the cases in which antibiotics were administered and those in which they were not. These results suggest that clinicians should administer antibiotics, taking into consideration their influence on patients’ microflora.