Soaring costs health care are seriously impacting on the Japanese healthcare insurance system, necessitating a reduction in such expenses. Simply lowering healthcare cost, however, could undermine the quality of services, pointing to the need to implement such cuts in tandem with the appropriate allocation of health care spending. One approach consists of burden of illness (BOI) and cost of illness (COI) studies, to quantitatively analyze the actual impact that illness has on society. We conducted a socioeconomic analysis of pneumonia, the fourth largest cause of death in Japan and the illness most often encountered, making comparisons with similar studies in the United States (US) and Europe. Results yielded the following factors:(1) Hospitalization is high at 70%(2) Compared to outpatient examination and treatment, the cost of hospitalized examination and treatment is far higher (¥21, 240 versus ¥284, 370) (3) Hospitalized examination and treatment costs in Japan are lower than those in the US and Europe. We concluded that these findings would play a valuable role in support of healthcare budget reallocation in public healthcare, while also serving as a sound health economic indicator in establishing guidelines for more effective diagnosis and treatment of pneumonia in Japan.

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Bacterial meningitis is a serious infectious pediatric disease whose common pathogens are Haemophilus influenzae and Streptococcus pneumoniae. Trends in antimicrobial susceptibility of both strains must be known for initial treatment of bacterial meningitis. We measured minimum inhibitory concentration of these 2 strains. Ceftriaxone (CTRX) is most susceptible for H. influenzae and panipenem (PAPM) for S. pneumoniae. We measured the fractional inhibitory concentration index (FIC index) to evaluate the antagonism of CTRX and PAPM in conbination. We did not find antagonism in the FIC index. Based on this data, we consider that the combination of CTRX and PAPM is better for initial treatment of bacterial meningitis than the combination of ABPC and CTX.

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The susceptibilities of Pseudomonas aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens to four types of carbapenems were examined using the broth micro-dilution method. All strains were isolated from various clinical samples obtained from patients of the Kawasaki Municipal Hospital between October 2001 and February 2002. An inoculum size of 10₅ cfu/mL was used.
1. The MIC₅₀S and MIC₉₀S of the carbapenem antibiotics against 95 strains of P. aeruginosa were as follows: imipenem (IPM), 2μg/mL for MIC₅₀ and 32μg/mL for MIC₉₀; panipenem (PAPM), 8μg/mL and 32μg/mL, respectively; meropenem (MEPM), 1μg/mL and 8μg/mL, respectively; and biapenem (BIPM), 1μg/mL and 16μg/mL, respectively. The frequencies of strain resistance to IPM, PAPM, MEPM and BIPM (MIC≥16μg/mL) were 26.3%, 41.1%, 6.3% and 16.8%, respectively.
2. The MIC₅₀s and MIC₉₀s of carbapenem antibiotics against 47 strains of H. influenzae were as follows: IPM, 1μg/mL for MIC₅₀ and 4μg/mL for MIC₉₀; PAPM, 1μg/mL and 4μg/mL, respectively; MEPM, 0.12μg/mL and 0.5μg/mL, respectively; and BIPM, 1μg/mL and 8μg/mL, respectively. The frequencies of strain resistance to IPM, PAPM and BIPM (MIC≥8μg/mL) were 2.1%, 6.4% and 10.6%, respectively. However, strain resistance to MEPM (MIC≥1μg/mL) was not observed.
3. No carbapenem-resistant strains of K. pneumoniae, E. cloacae or S. marcescens were detected.
4. We did not detect any strain of P. aeruginosa that could produce IMP-1 metallo β-lactamase. Although the number of carbapenem-resistant strains of P. aeruginosa did not increase significantly compared with past records, the continuous surveillance of resistance to carbapenem antibiotics in clinical isolates is important.

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We made a comparative study of antimicrobial activity in Pseudomonas aeruginosa isolated from blood culture. We divided P. aeruginosa chronologically into 3 periods: Period I (before 1987), Period II (1989-1993), and Period III (1995-1999). The minimal inhibitory concentration (MIC), MIC₅₀, and MIC₉₀ were measured to 13 antibiotics: piperacillin (PIPC), ceftazidime (CAZ), cefepime (CFPM), cefozopran (CZOP), amikacin (AMK), tobramycin (TOB), meropenem (MEPM), imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP), levofloxacin (LVFX), ciprofloxacin (CPFM), sparfloxacin (SPFX), and norfloxacin (NFLX). In measurement MIC, we followed the Japanese Chemotherapy Association standard method. Intermediate and Resistant (IR) rates (%) were calculated according to NCCLS document (M 100-S 12) measuring MIC.β-lactam antibiotics, MIC₅₀ and MIC₉₀ were the same or 1-fold difference during Period I to Period III. Other antibiotics, MIC₅₀ and MIC₉₀ were the same or 2-fold difference during Period I to Period II. MIC₅₀ and MIC₉₀ at Period II and Period III marked changed strinking resistance. When we compared the IR rate (%) of Period I and Period II, we found increasing PIPC, IPM/CS, MEPM, CPFX, and NFLX, while we found decreasing CAZ, CFPM, CZOP, LVFX, AMK, and TOB. Comparing the IR rate (%) the Period II with Period III, we found a decrease in only PIPC and an increase in all other antibiotics. We concluded that, in addition to MIC (MIC₅₀ and MIC₉₀), the IR rate should be added to antibiotics susceptibility surveys of P. aeuginosa. And it is necessity for empiric therapy to choice proper antibiotics, according to antibiotics susceptibility survey's result in each facility.

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We examined mutations in the quinolone-resistance-determining regions (QRDR) of gyrA and parC genes in 77 clinical isolates of Pseudomonas aeruginosa and compared the susceptibility of these isolates to NM 394, an active form of the prodrug prulifloxacin, with those to ciprofloxacin (CPFX), levofloxacin (LVFX), and gatifloxacin (GFLX). Of the 77 strains, 24 isolates exhibited an amino acid replacement in the GyrA or both the GyrA and ParC regions as a result of mutations in gyrA or both gyrA and parC, respectively. All of the 24 isolates had amino acid replacements in GyrA; none ofthe strains had amino acid replacements restricted to ParC. Amino acid replacement in GyrA but not in ParC was found in 6 isolates whose susceptibility to NM 394 was decreased; the susceptibilities of these 6 isolates to CPFX, LVFX and GFLX were also decreased. Amino acid replacement in GyrA and ParC was found in 18 isolates that were highly resistant to NM 394, LVFX, CPFX and GFLX. The short-term bactericidal activity of NM 394 at the MIC concentration against strains with or without amino acid replacement in GyrA or both GyrA and ParC was similar. The short-term bactericidal activities of CPFX and LVFX against strains with amino acid replacements in GyrA or both GyrA and ParC were lower than those against the strains with no amino acid replacements. These results demonstrate that the bactericidal activityof NM 394 against strains with a mutation in their type II topoisomerase genes was higher than those of CPFX and LVFX.

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As increasing numbers of patients with chronic renal failure survive, the incidence of malignant tumors as a complication in these patients has grown. To treat patients with smallcell lung cancer with chronic renal failure, we conducted chemotherapy with carboplatin (CBDCA) plus etoposide (VP-16) in combination with hemodialysis. Case 1, a 64 year old man, suffered from chronic renal failure due to membranous nephropathy and IgA nephropathy. He was diagnosed as having stage II a smallcell lung cancer. We administered 2 courses of chemotherapy with CBDCA +VP-16 and judged the result as NC. Granulocytopenia of grade 3 was noted as the main side effect. Case 2 was a 73 year old man with chronic renal failure due to nephrosclerosis and maintained with hemodialysis 3 times a week. He was also diagnosed with stage i a smallcell lung cancer. Chemotherapy with CBDCA plus VP-16 was given for 2 courses, resulting in PR efficacy. Granulocytopenia of grade 4 was found in the first course, so doses were reduced in the second course. AUC of CBDCA and VP-16 was maintained by monitoring blood concentrations in both case so. Although patients with chronic renal failure are considered highrisk in anticancer chemotherapy, it is safely conducted in combination with hemodialysis and monitoring blood concentrations of CBDCA and VP-16.

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