Amebiasis caused by ingestion of cysts of the protozoan parasite Entamoeba histolytica through fecally contaminated food develops when cysts pass through the stomach and are excystated in the small bowel, forming trophozoites in the large bowel. Some trophozoites invade the colon mucosa, produce ulcers, and cause amebic colitis. Others invade the portal vein, lodge in the liver, and form a liver abscess. Amebic infection is much more common in tropical developing nations. In industrialized countries, travelers from developing countries, residents of the mental institutions, and men who have sex with men (MSM) are at increased risk for amebiasis.Invasive amebiasis, e. g., colitis and liver abscesses, should be treated with metronidazole, which is effective for all tissues and usually engenders an effective response. Metronidazole therapy is followed by paromomycin, or diloxanide furoate, which are non absorbed luminal agents that prevent relapse by eradicating residual cysts in the colon. Luminal agents are not approved in Japan, but are provided by the Research Group on Chemotherapy of Tropical Diseases, which is part of the Research on Health Sciences Focusing on Drug Innovation, supported by the Japan Health Sciences Foundation. Early diagnosis and treatment of amebiasis is important when clinicians see watery and bloody diarrhea, abdominal pain, and fever in travelers from developing countries or in MSM patients.

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Using cephem antibiotic S-1090, cefcapene, cefdinir, cefpodoxime, and cefditoren, which exhibit different protein binding properties, we evaluated the relationship between therapeutic efficacy against Staphylococcus aureus rat thigh infection models and the concentration at the infection site.
Extracellular free concentrations in the thigh muscle, determined by microdialysis, were significantly smaller than total concentrations in plasma.The free concentration in extracellular muscle fluids was similar to the free concentration in plasma, which was calculated from the total concentration in plasma and rat serum protein binding.
The therapeutic efficacy of CFPN and S-1090 against S.aureus in the rat thigh infection model was determined. The dosage of S-1090 and CFPN, which caused 2 log reduction of viable cells in the thigh muscle compared to the initial inoculum, was 4.73 and 7.16mg/kg.The time above MIC at these dosages, calculated from extracellular and free concentrations in thigh muscles or free concentrations in plasma, was between 23 and 33%.
These results showed that free concentration in the muscle was as low as the free concentration in plasma, and that S-1090 showed good therapeutic efficacy in rat thigh infection models when T>MIC at infected sites was between 23 and 33%.

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MICs of antimicrobial agents were tested against CTX-M-2 group β-lactamase producing ESBL Proteus mirabilis isolated from 148 clinical specimens gathered from May to July 2005.
MICK₉₀ of ceftibuten (1μg/mL), ceftazidime (0.5μg/mL), cefmetazole (4μg/mL), latamoxef (≤0.25μg/mL), imipenem (2μg/mL), meropenem (≤0.25μg/mL), and aztreonam (2μg/mL) indicated high susceptibility toward these agents. Ampicillin, piperacillin, cefazolin, and cefotaxime showed very high MIC₉₀s (≥256μg/mL).
MIC₉₀ of minocycline was high (128μg/mL), whereas those of aminoglycosides amikacin, tobramycin, and gentamicin were 8, 16, and 16μg/mL. MICs of quinolones levofloxacin, ciprofloxacin, and gatifloxacin fluctuated widely from≤0.25-≥256μg/mL, ≤0.25-≥256μg/mL, and≤0.25-128μg/mL for each agent.
Infection control of ESBL producing gram-negative rods is very important at a medical institution. Furthermore, susceptibility tests play an important role in the implementation of effective control measures.

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Through a nationwide, collaborative, multicenter survey to investigate the pathophysiological profile of hospital-acquired pneumonia (HAP) and the use of first-line antibiotics, we evaluated the clinical position of meropenem (MEPM) in the initial therapy of HAP. A prospective survey was conducted of consecutivelyenrolled patients with HAP in the period from June 2002 to May 2004. Data were collected for a total of 1, 460 patients from 254 institutions across Japan.Among the cases analyzed for patient profiles (1356 patients), 661 cases were treated with MEPM among the first-line antibiotic. Of the MEPM-treated cases, monotherapy accounted for 76.6%. Among cases treated with MEPM combination therapy, clindamycin was used in 24.5%, followed in descending order by tetracyclines and aminoglycosides. MEPM was preferably used for serious cases or cases having many risk factors defined in the Japanese Respiratory Society Guidelines for Management of HAP in Adults. As for the distribution of the disease type, moderate pneumonia with a risk factor or severe pneumonia [Group III: type C] and pneumonia with specific conditions [Group IV: type D-H] accounted for 91.7% of all cases. The response rate was 54.4% when MEPM was used as a first-line medication, and 47.2% when carbapenems were not used. Most of the MEPM-treated patients were the dosage which is normal in Japan (0.25-0.5g×2/day). As the main causative organisms of HAP were antibioticresistant bacteria such as Pseudomonas aeruginosa, future revisions of the HAP guideline should incorporate consideration of antibiotics dosage based on the PK/PD theory. As for safety, main adverse drug reactions in MEPM-treated patients were hepatic function disorder. Unlabelled serious adverse drug reactions were not reported. In conclusion, the results from this study suggest that MEPM plays an important role in the initial therapy of HAP.

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An oral cephalosporin antibiotic, cefcapene pivoxil (CFPN-PI), was administered to 128 pediatric patients in a multi-centered post-marketing clinical trial, and its pharmacokinetics efficacy, and safety were investigated. The results obtained are described below.
1. Population Pharmacokinetics
CL/F and Vd/F were in proportion to body weight, and there were no differences in pharmacokinetic data between patients under 10kg and patients over 10kg (110 evaluated patients).
2. Efficacy
The efficacy rate against respiratory infections and urology infections were very high (88.1% and 100%, respectively).
3. Bacteriological Efficacy
CFPN-PI displayed potent antibacterial activity against various bacteria, including Penicillin-resistant Streptococcus pneumoniae (PRSP).
4. Safety
Adverse drug reactions manifested as clinical symptoms were observed in 18 of the 128 cases (18 events). All events except 1 rash consisted of gastrointestinal symptoms. Adverse drug reactions in the form of abnormal laboratory test values were observed in 11 of 116 cases (15 events), including 4 cases each AST elevation and ALT elevation.
The above results, confirmed that CFPN-PI is efficacious, safe and yields favorable pharmacokinetic data when administered to pediatric patients, including infants (except for newborns), at the approved dosage and administration method.

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