In a rat model of Escherichia coli epididymitis, Northern blot analysis and reverse transcriptionpolymerase chain reaction (RT-PCR) demonstrated that expression of IL-6 mRNA in the epididymis increased, reached a maximum as early as 6 h after bacterial challenge, and then decreased. No signals of expression detected on the contralateral side or in the controls. Expression of other cytokines (IL-1β, IL-2, TNF-α, IFN-γ) was also determined by RT-PCR. After bacterial challenge, IL-β mRNA was detected in the epididymis as well as IL-6 mRNA. The TNF-α mRNA signal, but not of IFN-γ mRNA, increased greatly after bacterial challenge, although both TNF-α and IFN-γ mRNAs were detected in uninfected epididymis. Histopathological examination showed no apparent changes at 6 h after infection, and only mild interstitial cellular infiltration at 24 h. Immunohistochemical examination showed that epithelial cells produced IL-6. Cultured epithelial cells also expressed IL-6, IL-1β, and TNF-α mRNA after lipopolysaccharide stimulation. The results suggest that mRNAs for specific cytokines are expressed locally as early as 6 h in response to bacterial genital infection before the histopathological changes. This rapid expression may be important in host defense against local genital infection.

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Recent emergence of vancomycin resistance in methicillin-resistant Staphylococcus aureus (VRSA) has posed a new threat to hospital infection control and antibiotic chemotherapy. The first vancomycinresistant Staphylococcus aureus strain, Mu 50, was isolated in 1996. The level of resistance in VRSA, as judged by minimal-growth inhibitory concentration (8μg/mL), is low compared to that of vancomycinresistant enterococci (VRE). Hetero-VRSA strains exhibit vancomycin MIC levels equal to or less than 4μg/mL, but, they show a heterogeneous type of resistance to vancomycin. Exposure of hetero-VRSA to concentrations of vancomycin of 4μg/mL or higher reproducibly generates VRSA with a frequency of 10^-6 or higher. This article provides an historical overview of the emergence of glycopeptide resistance in staphylococci and considers its mechanism of resistance.

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To investigate in vitro antimicrobial activities and bactericidal activities of meropenem (MEPM), imipenem (IPM), amikacin (AMK) and sulbactam/ampicillin (SBT/ABPC) against 19 clinical strains isolated from the blood of septic patients with hematologic diseases, MICs at 24h and MBCs at 6h (6h-MBCs) or 24h (24h-MBCs) after the addition of antibiotics were determined. All strains tested showed relatively high susceptibility (MIC≤1.56μg/mL) to some of the antimicrobials tested. Against Escherichia coli and Klebsiella pneumoniae, MEPM (MIC≤0.05μg/mL), IPM (MIC≤0.39μg/mL) and AMK (MIC≤6.25μg/mL) showed high antimicrobial activities, but the antimicrobial activities of SBT/ABPC (12.5≤MIC≤50μg/mL) were low. Although two carbapanem-resistant strains (MIC=12.5μg/mL) and an AMK-resistant strain (MIC=12.5μg/mL) were observed, other three strains of Pseudomonas aeruginosa tested showed relatively high susceptibilities to these antibiotics. Against Staphylococcus epidermidis, the other coagulase-negative staphylococci (CNS) and streptococci, MEPM (MIC≤1.56μg/mL), IPM (MIC≤0.39μg/mL) and SBT/ABPC (MIC≤3.13μg/mL) showed high antimicrobial activities. Since most of the 24h-MBCs of antibiotics tested were equivalent to each MIC, it was suggested that exposure to the antibiotics at MIC for 24h showed sufficiently high bactericidal activities. On the other hand, some of the 6h-MBCs were much higher than each MIC. This result suggested that the antibiotics tested required higher concentrations than the MIC to show sufficient bactericidal activity against some isolates, in practical use. The combined effects of carbapenems and AMK or SBT/ABPC against 30 clinical strains isolated from septic patients were examined by checkerboard titration assay. Against E. coli and K. pneumoniae, the combination of MEPM and SBT/ABPC (addition: 7 strains, indifference: 1 strain in 8 strains tested), against S. epidermidis and the other CNS, the combination of MEPM and AMK (synergism: 5 strains, addition: 4 strains in 9 strains tested), Enterococcus faecalis and streptococci, the combination of carbapenem (MEPM or IPM) and SBT/ABPC (synergism: 1 strain, addition: 4 strains in 5 strains tested) showed the highest combined effect in this study. Interestingly, against P. aeruginosa, MEPM (synergism: 7 strains, addition: 1 strain in 8 strains tested) showed a greater combined effect than IPM (addition: 5 strains, indifference: 3 strains in 8 strains tested) in combination with AMK. As far as these results are analyzed, it is suggested that for sepsis caused by E. coli or K. pneumoniae, monotherapy with carbapenems, especially meropenem, or combination therapy with carbapenems and AMK or SBT/ABPC is effective. For pseudomonal infection, combination therapy with MEPM and AMK is effective. The findings also suggest that monotherapy with carbapenems or SBT/ABPC, or combination therapy with carbapenems and AMK or SBT/ABPC is suitable for bacterial infection caused by CNS or streptococci.

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In order to reconfirm the optimal dose and search for the clinical benefits of biapenem (BIPM), a parenteral carbapenem antibiotic, in the treatment of acute exacerbation of chronic bronchitis, a randomized, three-group comparative study against imipenem/cilastatin (IPM/CS) as a comparator was performed by using a telephone registration method, and the following results were obtained. BIPM at 300 (group L) or 600 (group H) mg/day in two-divided doses and IPM/CS at 1, 000 mg/1, 000 mg/day (group C) in two-divided doses were systemically administered. The duration of treatment was within 14 days. The number of patients evaluated for clinical efficacy out of the total 35 patients registered was 32 cases (L group 10 cases, H group 10 cases, C group 12 cases).
1) Clinical effects: The efficacy rates were 100%(10/10). 90.0%(9/10), and 91.7%(11/12) in group L, H, and C, respectively. For the evaluation of early onset after 3 days of treatment, the efficacy rates were 60.0%(6/10), 90.0%(9/10), and 58.3%(7/12) in group L, H, and C, respectively.
2) Bacteriological effects: The bacterial eradication rates were 100%(6/6), 100%(3/3), and 100%(9/9) in groups L, H, and C, respectively.
3) Side effects were observed at a rate of 8.3%(1/12) in group C. The severity of the drug fever/drug eruption was moderate. No side effects were observed in group L and H.
4) Abnormal laboratory findings were observed at a rate of 20%(2/10) in group L, 33.3%(4/12) in group H, and 20%(2/10) in group C. These abnormal findings were mild.
5) Usefulness: The usefulness rates were 100%(10/10), 90%(9/10), and 83.3%(10/12) in groups L, H, and C, respectively. There were no statistical differences in every evaluation among the 3 groups.
The rate of efficacy on day 3 that reflects the early response of the drug treatment is 600 mg a day and the highest efficacy rate. These results demonstrated that the 600 mg a day was the appropriate clinical dosage of BIPM with an early clinical effect in the treatment of chronic bronchitis from the point of view of efficacy and safety.

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The clinical efficacy, safety and usefulness of biapenem (BIPM), a carbapenem antibiotic for injection, were evaluated in lower respiratory infections in a comparative study with imipenem/cilasstatin (IPM/CS). BIPM and IPM/CS were administered by intravenous drip infusion at a dose of 300 mg twice daily and 500 mg/500 mg twice daily. The duration of treatment was within 14 days. The following results were obtained.
1. A total of 214 cases were enrolled in this study, consisting of 103 in the BIPM group and 111 in the IPM/CS group. The clinical efficacy was evaluated in 88 of the BIPM group and 93 of the IPM/CS group, the overall safety was evaluated in 101 of the BIPM group and 110 of the IPM/CS group, and the usefulness was evaluated in 89 of the BIPM group and 101 of the IPM/CS group.
2. The clinical efficacy rates were 93.2%(82/88) in the BIPM group and 91.4%(85/93) in the IPM/CS group. The 90% confidence interval of the difference between the two groups was-5.8% to 9.4%, and the clinical non inferiority of BIPM to IPM/CS was demonstrated. For the evaluation of early onset after 3 days of treatment, the early clinical efficacy rates were 84.1%(74/88) in the BIPM group and 76.3%(71/93) in the IPM/CS group, with no significant difference between the two groups.
3. The bacteriological eradication rates were 89.1%(41/46) in the BIPM group and 97.5%(39/40) in the IPM/CS group, with no significant difference between the two groups.
4. Side effects were observed at a rate of 1.9%(2/103) in the BIPM group and 6.3%(7/111) in the IPM/CS group, with no significant difference between the two groups. Abnormal laboratory findings were observed at a rate of 26.2%(27/103) in the BIPM group and 43.2%(48/111) in the IPM/CS group, with significant difference between the two groups. The safety rates were 98.0%(99/101) in the BIPM group and 96.4%(106/110) in the IPM/CS group, with no significant difference between the two groups.
5. The usefulness rates were 88.8%(79/89) in the BIPM group and 81.2%(82/101) in the IPM/CS group, with no significant difference between the two groups.
These results demonstrate that BIPM is a useful drug for the treatment of lower respiratory tract infections.

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The therapeutic efficacy of levofloxacin (LVFX) was evaluated in the patients with complicated urinary tract infections (UTI). The patients were orally administered 100 mg of LVFX t. i. d. for 7 days. Some patients with severe symptoms or refractory UTI were orally administered 200 mg of LVFX t. i. d. for 7 days. The therapeutic efficacy rate was found to be 77.5% in 71 cases which satisfied the criteria of the Japanese UTI committee (4 th edition). Recurrence was determined 2 weeks after the completion of the treatment. Clinical symptoms appeared in 29.2% of the cases, and bacteriuria (≥10⁴/mL) was observed in 57.9% of the cases. Enterococcus faecalis and Escherichia coli were the dominant bacteria in 125 urinary isolates before the treatment. The rate of bacterial eradication was 89.6% at the completion of the treatment. Six strains of Enterococcus faecalis, 2 of CNS, 1 of Staphylococcus epidermidis, 1 of Citrobacter freundii, and 3 of Pseudomonas aeruginosa were not eradicated by the treatment. Staphylococcus species and Candida species frequently emerged at the completion of the treatment. Gram-positive bacteria, such as Enterococcus and Staphylococcus species were frequently isolated at the recurrence. Decreased susceptibility to LVFX was observed in Staphylococcus species isolated at the completion of treatments or at recurrence, however, the susceptibility of other bacteria to LVFX did not change. We conclude that LVFX is an effective agent for the treatment of complicated UTI. However, the high incidence of bacterial recurrence by Gram-positive bacteria should be noted.

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A 49-year-old woman was diagnosed with non-Hodgkin's lymphoma (IBL-like T cells) and received combination therapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Shortly there after, she suffered a relapse and was treated with multi-agent chemotherapy, but the skin eruptions became worse and her lymph nodes were enlarged. With the patient's quality of life in mind, treatment with low-dose oral etoposide was initiated in August 1997. On July 2, 1998, herpes zoster lesions were noted in the anal region, and acyclovir, 4 g/day, was administered orally for seven days. The pain diminished, but the vesicles persisted. On July 20, vesicles developed over her entire body, and generarlised herpes zoster was diagnosed. Vidarabine (600 mg/day) was administered intravenously for six days, but the patient died of respiratory failure after rapid clinical deterioration. At autopsy, immunohistochemical staining with anti-varicella zoster antibody was positive for varicella-zoster virus in the lungs as well as in all other organs examined. The cause of the dissemination of the virus throughout the body was impairment of cellular immunity by the primary disease, irradiation, and chemotherapy. This emphasizes that chemotherapy should be administered to such patients with care.

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