Chinese traditional herbal medicine was introduced to Japan through the introduction of Buddhism from China in the 6th century and was established as Kampo (Japanese herbal) medicine during the Edo era after some modification, having a clinical history of more than 2000 years. Because Kampo medicine has often been used for the treatment of disease difficult to cure by orthodox medicine, it plays an important role in a medical treatment in Japan. Kampo medicine has been used as the decoction of the formula which were prescribed by several component herbs. Spray dried granule form was also developed for modern-day therapy. The action of orthodox medicine directs specifically to the nature and functions of a disease, whereas the action of Kampo medicine attempts to harmonize the disturbed pathophysiological condition of the patient (“sho, ” clinically) as a whole to eventually equilibrate a normal physiological environment in the system.
Although it has been believed that Kampo medicines is suitable for the treatment of chronic disease, several Kampo medicines have also been used for the treatment of infectious diseases such as typhoid fever which was described in the classical text book, Shanghanlun. Kampo medicine has been used separately depending on the progress of infectious disease and the decline of resistance of the body. Kampo medicine is effective for the treatment of several infectious diseases such as viral hepatitis, influenza viral infection, and MRSA and Helicobacter pyroli infections, proved by basic and clinical studies. Some Kampo medicines show direct action against infected microbes and defensive action through immunostimulation. Kampo medicine is expected to show preventive effects in elderly patients with decreased body action in transition to the serious stage of infectious disease.
Medicinal herbs used in Kampo medicine also have a possibility to develop new antiinfectious agents such as the potent antimalarial drug Artemisinin.

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We studied the antimicrobial activity of 42 antimicrobial agents against 143 Escherichia coli isolates identified structural gene of extended-spectrum β-lactamase. The 143 isolates were from 133 patients who visited 31 hospitals in northern Kyushu and Yamaguchi. ESBL items were UOE-2 (CTX-M-14 or-18) type 34, CTX-M-2 type 43, CTX-M-3 type 17, UOE-1 type (CTX-M-15) 24, CTX-M-12 type 3, SHV-12 type 20, and TEM type 2. Against UOE-2 and CTX-M-2 ESBL producing isolates ceftazidime, cefepime, and aztreonam showed comparatively low MIC, and against TEM and SHV type ESBL producing isolates cefotaxime, cefpirome, and cefepime showed comparatively low MIC. Against all ESBL producing isolates, most cephalosporins and penicillins showed high MIC. Carbapenems (imipenem and meropenem) were the most active of all agents tested. The growth of all isolates was inhibited at 0.25μg/mL of meropenem and 0.5μg/mL of imipenem. Cephamycins, which have methoxy substitute at position 8, also have good activity against ESBL producing E. coli. Cefmetazole had a resistant, and latamoxef and flomoxef were susceptible against all isolates. Regarding β-lactam combined with β-lactamase inhibitor, against CTX-M type ESBL producing isolates piperacillin/tazobactam showed good activity than cefoperazone/sulbactam, while against TEM and SHV type ESBL producing isolates cefoperazone/sulbactam showed good activity than piperacillin/tazobactam. Although the activity of ampicillin/sulbactam and amoxicillin/clavulanic acid improved compared to ampicillin and amoxicillin alone, the improved MIC was not less than the breakpoint MIC. Regarding non-β-lactams, quinolones (ciprofloxacin, levofloxacin, and gatifloxacin), tetracycline, gentamicin, and cotrimoxazole showed less activity, while minocycline and fosfomycin were susceptible more than 75% against ESBL producers except UOE-2 producers. Early detection of ESBL producers and early infection control are vital importance to preventing ESBL producer outbreaks.

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We evaluated the influence of albumin on protein binding of antimicrobial drugs most widely used in neonates and the possible correlation between protein binding and gestational weeks or birth weight. Protein binding of ampicillin (ABPC) in neonates was not associated with the amount of albumin, and was slightly higher than that in adults. Protein binding of cefotaxime (CTX), flomoxef (FMOX), cetrazidime (CAZ), cefozopran (CZOP), ceftriaxone (CTRX), and aztreonam (AZT) were similar to or lower than those in adults reported in the literature. Protein binding was compared between neonates born < 37 weeks of gestation and those born ≥37 weeks of gestation. Protein binding of CTX was significantly lower in neonates born <37 weeks of gestation (19.7%) than in those born ≥37 weeks of gestation (30.2%), but protein binding of other drugs did not differ markedly between groups. Protein binding was also compared between neonates with birth weights of <2, 500 g and ≥2, 500 g. Protein binding did not differ significantly for any drug between groups. Evaluation by gestational week or birth weight showed lower protein binding in premature neonates and low birth-weight neonates thanin adults.
Pharmacokinetic parameters evaluated in this study suggest that an increase in the plasma drug-free form ratio does not affect the effectiveness or safety of antimicrobial drugs.

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We evaluated the influence of antimicrobial drugs on free bilirubin concentration in neonates. ABPC, CTX, and FMOX increased the free bilirubin concentration ratio to total bilirubin concentration [free bilirubin ratio (UB/TB)], while CZOP and CAZ moderately increased UB/UT. CTRX and AZT affected UB/TB negligibly. Evaluation by birth weight showed a slight increase in UB/UT by ABPC, CTX, FMOX, CAZ, and CZOP in neonates with low birth weight, but CTRX and AZT had no influence on UB/UT. Total bilirubin concentration was significantly decreased compared to the control group after drug administration, while free bilirubin concentration was decreased only slightly. These results suggest that the 7 antimicrobial drugs slightly reduced plasma protein binding but negligibly influenced free bilirubin concentration and may thus be safe for use in the neonates.

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