Antibiotic products, like vaccines, had been regarded as “biological products”, due to their natural substance quality from being produced by microorganism fermentation. Consequently, they were dealt with legally as “inspection objects” to be subjected to the national certification program.

In the early stages, all processes of fermentation, extraction, purification and formulation of antibiotic products were unskilled practices. There were concerns about unknown toxic, pyrogenic or depressive substances that might be preparation contaminants that could possibly be administered to patients. Therefore, biological safety tests using mice, rabbits and cats had been imposed on antibiotic preparations in order to detect the existence of any such harmful substances.

Antibiotic product development was so remarkable that many chemical derivatives possessing higher activity, or improved pharmacological characteristics, had been introduced into clinical use. Under such circumstances, it was determined that the traditional ways of dealing with antibiotics as biological products were irrational. A more rational approach would be to handle the development in a manner similar to that used for general chemical drugs. As a result, the national certification of antibiotic products was abolished and the “Minimum Requirements for Antibiotic Products of Japan” was integrated into the “Japanese Pharmacopoeia”. During the integration process, it was necessary to revise animal tests that did not conform to the principle of pharmacopoeia. This was accomplished by either the complete abolishment of or replacement with appropriate chemical tests.

In this report, we investigated, analyzed and discussed the biological safety tests imposed on antibiotic products for their importance of enactment, the transition of experimental procedures, and the sequence of events involving the reconsiderations and abolishments.

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.