Natural compounds produced by microorganisms have greatly contributed to the improvement of human health. Actinomycete and fungal strains are known to produce various secondary metabolites in their culture broths. The Kitasato Ōmura-Drug Discovery Group has found over 500 new compounds from these microorganisms. The production strains have been preserved by a long-term preservation method as Kitasato Microbial Library (KML).

The physicochemical properties of compounds produced by the preserved strains and fresh isolates were analyzed, and compared with a database. Subsequently, predicted new compounds were purified from culture broths and their structures were determined by NMR and MS. 35 compounds have been discovered by this approach, called Physicochemical screening. A compound, designated iminimycin, containing an iminium ion was discovered from the culture broth of Streptomyces griseus OS-3601. This KML strain has been stored for a long time as a streptomycin producing strain. Named trehangelin was discovered from rare actinomycete Plolymorphospora rubra K07-0510 isolated from the roots of orchid collected from Iriomote Island, Japan. Trehangelin A, the main compound, binds angelic acids to the 3, 3’ positions of trehalose. It has been found that the compound showed cytoprotective effect and accumulation of procollagen type I C-peptide, and further research is currently in progress.

It is shown that microorganisms are an inexhaustible gold mine of new natural compounds.

Background. Patients staying in intensive care units (ICU) usually have a variety of comorbidities including hospital-acquired infections (HAI), and can often be received antimicrobials as treatment or prophylaxis for HAI. Administration of any antimicrobials ought to affect normal bacterial flora of the patients, which could be a risk for antimicrobial resistance (AMR). Active surveillance culture in ICU is known to be one of the useful measures against AMR. The aim of this study is to evaluate the effects of antimicrobials on bacterial flora of nasal mucosa of the patients in ICU.

Methods. Patients were eligible for this study if they stayed in the ICU at Yamagata Prefectural Central Hospital from June 2015 through September 2016. Active surveillance was done by nasal swab culture from all the eligible patients once a week until they left from ICU. Bacterial or fungal cultures were isolated from the culture samples and detected by using VITEK2 microbial identification system (SYSMEX bioMérieux). Clinical parameters were retrospectively assessed in the study group. Data were statistically analyzed using JMP 11 software.

Results. A total of 614 nasal swab samples from 364 patients were subjected to microbial cultures. Among 614 samples, 550 bacterial or fungal cultures were isolated and 64 were negative culture. Four hundred fifty-nine samples were obtained as initial ASC (length of ICU stay <1 week), and 155 were follow-up ASC (length of ICU stay ≥1 week). The isolation of Streptococcus species was significantly lower in follow-up ASC than initial ASC; whereas those of Enterobacteriaceae, Glucose non-fermenting gram negative rods, Candida species were significantly higher in follow-up ASC than initial ASC (p<0.05, Chi-square test). Furthermore, normal nasal bacterial flora was significantly decreased in patients with the following parameters: longer ICU stay and antibiotic use (p<0.05, Chi-square test). Multivariate analysis indicated that longer ICU stay and antibiotic use were the independent risk factors that could alter the nasal bacterial flora of ICU patients (Odds Ratio 1.06, per 1-week increase [95% confidence interval: 1.009–1.14] and 2.1 [1.2–3.7], respectively).

Conclusion. Administration of antibiotics cloud affect nasal bacterial flora in ICU patients. ASC would be a useful tool for infection control and antimicrobial stewardship in ICU.