The therapeutic effect of fosfomycin at a large oral dose against intestinal infection with Escherichia coli O157: H7 was investigated in a mouse model previously described. Three ICR strain (IQI, germ free) mice aged 5 weeks were challenged orally with a verotoxin-producing strain NK2 of E. coli O157: H7. The high levels of viable cells, 3.0 X ¹⁰¹⁰-3.4 × ¹⁰⁸⁰ CFU/g, were excreted into the feces of the untreated mice for 3-10 days after bacterial challenge. Fosfomycin was given at an oral dose of 600 mg/kg twice a day for 6 days to 3 mice infected with E. coli 0157: H7, beginning 3 days after the challenge, to investigate changes in viable cell counts and to measure fecal concentrations of fosfomycin. Results were that the viable cells decreased markedly, (from about 10¹⁰ CFU/g before dosing) to ¹⁰³-¹⁰⁴ CFU/g on day 1 of dosing, and no viable cells were detected in the feces from day 2 of dosing onwards. During the period, no verotoxin was detected in fecal samples collected from all 6 test mice (including 3 control mice). Concentrations of fosfomycin in the feces after dosing were 34.6-47.4 μ g/g in all the mice on day 1 of dosing, and 62.4 and 131.1 μ g/g in 2 of the mice on day 6 after dosing, but nondetectable otherwise. These results suggested that a marked decrease in viable cells without the liberation of verotoxin was observed in the feces of infected mice after fosfomycin was given orally in a massive dose.

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Thirty five clinical isolates of Escherichia coli O157 were subjected to verotoxin-production, susceptibility and verotoxin (VT) release testing against various antibiotics.
1) Verotoxin-production of clinical isolates of E. coli
Three strains produced only VT-2 and an other 32 strains produced both VT-1 and VT-2 in our tested 35 clinical isolates of E. coli O157.
2) Susceptibility testing
Thirty five clinical isolates of E. coli O157 were subjected to susceptibility testing against 21 drugs of β-lactams, 5 drugs of quinolones and 10 other drugs. Only one strain was resistant to penicillins, whereas, an other 34 strains were susceptible to all drugs tested. Quinolones were most active against E. coil 0157, and its _MIC90s were 0.0125-0.1 μ g/ml.
3) Verotoxin release
The amounts of VT released from E. coli TK-806 were measured after exposure to 2 MIC of tosufloxacin (TFLX), kanamycin (KM) and fosfomycin (FOM). The amounts of VT were increased 64 fold after exposure to FOM for 2 h. On the other hand, no increase was observed in the case of TFLX and KM.
In the study described here, clinical isolates of verotoxin-producing E. coli O157 were tested for susceptibility to various antibiotics, and TFLX made E. coli release less VT than FOM did.

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We investigated the isolation frequency and O-serotype distribution of 550 isolates of Serratia marcescens from clinical specimens at the Juntendo University Hospital from 1991 to 1995. Of the 550 isolates, the most common were respiratory tract specimens including expectorates, aspirates and throat swabs, Urine, pus, and discharges were also frequent sources of specimens. Most isolates from pus and discharges derived from the skin, wounds and surgical drainage Isolates from blood and intravenous indwelling catheters were few (less than 5%). The distribu. tion of O-serotypes in this study was determined with the 16 anti-sera scheme. The most common O-serotypes were O5 (13.3%), O4 (10.5%) and complex types (17.0%). No isolates were identified as O1 or O11. Isolates of O4 and O5 were mainly found in respiratory tract specimens. More than 80% of complex types cross-reacted extensively between O12 and O14 antisera (O12/O14), which were frequently found in urine isolates from 1992 and 1993. During the past 5 years, non-typable strains slightly increased (19.6%). The overall result of the recent O -serotype distribution was different from that of previous reports in the 1980s. O4 was still a common serotype. O14, which was a major serotype in the 1980s, decreased in this study. In contrast, O5 and complex types (O12/O14) increased.

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The in-vitro susceptibility of 13 antimicrobial agents against a total of 550 clinical isolates of Serratia marcescens was determined by a broth microdilution method. The following antimicrobials were tested: piperacillin (PIPC), cefotaxime (CTX), ceftazidime (CAX), flomoxef (FMOX), cefpirome (CPR), aztreonam (AZT), imipenem (IPM), gentamicin (GM), amikacin (AMK), ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX) and sparfloxacin (SPFX). IPM and CPR were the mostactive with _MIC90, 1 μ g/ml and 2 μ g/ml, respectively. AZT and CAZ were also active _MIC90, 8 μ g/ml). The other β-lactam antibiotics (_MIC90), including PIPC (> 128 μ g/ml), CTX (32 μ g/ml) and FMOX (64 μg/ml) showed poor activity. GM and OFLX exhibited moderate activity (_MIC90, 4 μ g/ml). From 1991 to 1995, overall trends in resistance to almost all antimicrobials tested were reduced except in 1992 and 1994, and were lower than those of previous studies in the 1980s. Isolates in 1992 and 1994 showed that their resistance rates had increased. Susceptibility patterns among selected antimicrobials including PIPC, CTX, IPM, GM and OFLX were also evaluated. Of all isolates, 74% were susceptible to the 5 antimicrobials. Imipenem-resistant strains were found in 1992, and increased in 1994. Drug-resistant strains were observed in O3, O13, O14, O17 and complex types, but not in the common serotypes such as O4 and O5. Multiple-resistant strains with imipenem-resistance were observed in isolates of O13, O14 and the complex types (O12/O14), which were mainly derived from urine specimens.

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In order to investigate an effective treatment for multiple myeloma (MM), patients with advanced MM (stages II and III, and/or resistant to previous treatment) were treated using vincristine, cyclophosphamide, prednisolone, with or without interferon-α, or VCP (INF) protocol. Among 36 patients admitted to our hospital between January 1988 and September 1997, 34 patients (males, median age: 58 years, 53%≥ 60 years) were evaluated for response and therapeutic outcome. In out of 34 evaluable patients, we obtained 24 partial response (PR), 3 no change (NC), 7 progressive disease (PD) resulting in 70.6% of response. The median duration of response was 15 months (1.3 yr) and the median survival time for the PR patients was 26.5 months (2.2 yr) and that of the overall patients was 20.3 months (1.7 yr), respectively. Prognostic factors for the patients treated with this therapy were response to therapy, stage, serum creatinine, and serum β 2 microglobulin, and these factors were significantly related to survival time. The therapeutic benefit of adding IFN-α to this therapy was unclear since survival time was not significantly prolonged, compared with VCP therapy alone. Although VCP (IFN) therapy proved to be as effective as conventional combination chemotherapy against MM, more aggressive therapy such as high-dose chemotherapy with hematopoietic stem cell transplantation should be considered for younger patients with advanced MM and poor prognostic factors.

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