From January 2000 to March 2001, we studied pharmacokinetics of cefozopran (CZOP) in 9 newborns suspected of intrauterine infection, including 3 low-birth-weight infants of less than 2, 000 g and 3 infants with renal dysfunction.The mean gestational age of 3 low-birth-weight infants was 32.7 weeks and their mean birth weight was 1, 579g.That of full-term newborns was 3, 167g.The mean creatinine of 3 infants with renal dysfunction was 1.6 mg/dL.CZOP was administered by intravenous bolus injection at a dose between 19.6 and 25.0 mg/kg on examination day.The mean serum concentration of CZOP 30 minutes after injection in full-term infants was 45.8, μg/mL and that in low-birth-weight infants was 59.7μg/mL. The mean serum half-life in full-term infants was 2.31 hours and that in low-birth-weight infants was 2.21 hours.No significant difference was found between full-term and low-birth-weight infants.The mean serum concentration and half-life in 6 infants without renal dysfunction were 51.4±14.7μg/mL and 2.26±0.43 hours. The half-lives in infants with renal dysfunction were 9.31, 16.64, and 18.79 hours.

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Currently available antifungal agents for the treatment of invasive fungal infections are limited in number and usefulness.Thus, the development of novel antifungal agents, including new formulations of approved agents, with advantages over and/or complimentary to existing agents is urgently needed. Antifungal agents presently at different clinical development stages in the United States, Europe, and Japan include:(i) various lipid formulations of polyenes (particularly amphotericin B);(ii) hydroxypropyl-β-cyclodexrin formulations of itraconazole;(iii) new generation triazoles;and (iv) candins.Novel delivery systems utilized for the new formulations of polyenes and itraconazole substantially modulate the pharmacokinetics of the existing compounds, and may also be useful in enhancing the delivery of antifungal agents to infection sites.The new generation of triazoles, including voriconazole, posaconazole and ravuconazole, presently at advanced stages of clinical development exhibit an increased activity and expanded spectrum compared with fluconazole and generally demonstrate good pharmacological properties and low toxicity.Candins represent a novel class of antifungal agents that act by inhibiting the synthesis of (1→3)-β-glucan synthase, a key enzyme in fungal cell wall biosynthesis.Three compounds in this class, viz., VER-002, MK-0991 and FK 463, are fungicidal and active against various fungal pathogens and Pneumocystis carinii without cross-resistance to azoles and show excellent pharmacokinetics and low toxicity.These promising new agents are expected to become available in the near future and should constitute effective new options for the management of a variety of invasive fungal infections.

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A questionnaire on the prophylaxis of postoperative infection was conducted among surgeons in Japan to obtain a consensus on perioperative management of surgical patient colonized with methicillin-resistant Staphylococcus aureus (MRSA). The questionnaire was sent to 643 surgeons and recovered from 406 (63%), including 88 of 133 general surgeons (66%), 52 of 83 cardiac surgeons (63%), 45 of 82 neurosurgeons (55%), 50 of 91 orthopedists (55%), 56 of 83 gynecologists (68%), 63 of 87 urologists (72%), and 52 of 84 otolaryngologists (62%). The following strategies were consented to by more than 50% of all responses: ‘Keep hospital policies dealing with control of hospital infection’ and ‘Apply mupirocin ointment to the nose before the operation if the patient is a nasal carrier and expected to have major operation.’ More than 50% of cardiac, neurology and general surgeons reach the consensus that an antiseptic shower or bath is indicated for preoperative patients colonized with MRSA other than nares, such as axilla, inguen, or perineum.Less than 50% of all responses consented to ‘Administer anti-MRSA agent such as vancomycin, arbekacin, or teicoplanin to remove colonized MRSA.’ In spite of vigorous efforts, MRSA colonizing compromised patients scheduled to undergo major operation should be considered for the prophylactic use of anti-MRSA agents, for which a mean of 53% of each surgeon group reached consensus.

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A questionnaire was conducted among surgeons in Japan to obtain a consensus for selecting antimictobial prophylactic (AMP) agents for postoperative infection. The questionnaire was sent to 643 surgeons and recovered from 406 (recovery: 63%). Eighty-eight of 133 general surgeons (66%), 52 of 83 cardiac surgeons (63%), 45 of 82 neurosurgeons (55%), 50 of 91 orthopedists (55%), 56 of 83 gynecologists (68%), 63of 87 urologists (72%) and 52 out of 84 otolaryngologists (62%) replied and the consensus below were obtained. An AMP agent should be chosen based on their efficacy against pathogens expected to be contaminants, such as Staphylococcus spp., Escherichia coli, and Bacteroides fragilis group. Use an AMP agent that achieves a bactericidal concentrations at the operating site.Use an AMP agent that has few unfavourable effects.Use an AMP agent that minimally affects normal bacterial flora.Newer agents should be considered as therapeutics for postoperative infections. The most commonly used agents are the penicillins and first-and second-generation cephalosporins.

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The effectiveness of combination chemotherapy with estracyt and etoposide, which would enable ambulatory care, was studied in a multi-center collaborative study. Eighteen patients with recurrent prostatic cancer after endocrine therapy were administered estracyt 560 mg orally daily in four equal doses and 100 mg/m²/day etoposide i.v. for 3 days, every 4 weeks. The duration of treatment was 104 days on average (maximum 360 days). Eleven (61.1%) patients received 3 courses of treatment. After the end of 3 courses, performance status (PS) was improved in 2 patients, unchanged in 8, and worsened in only one patient, with improvement of pain being observed in 8 patients. Partial response (PR) was attained in 1 patient, no change (NC) in 5 and progressive disease (PD) in 5; there were 6 unevaluable patients, with the effectiveness rate being 9.1%. The rate of PR+NC was 54.5%, when cases with ability of ambulatory care keeping quality of life (QOL) were included in the cases of NC. The effectiveness of this combination chemotherapy, based on PSA levels only was 45.4% in more than PR and 81.8% in PR+NC. This regimen was more effective in patients less than 74 years old with comparatively good PS. In addition, this regimen could be satisfactorily administered on an ambulatory basis because hematological adverse reactions were scarce. This regimen can be repeatedly administered to ambulatory patients thereby maintaining that good QOL, however, the proximity effect is not so large.

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In this report, we show the activity of β-lactamase inhibitors against ESBL producers, inhibitor resistant β-lactamases and Toho-type β-lactamase producers. The MIC values of piperacillin (PIPC) against each β-lactamase producer were 32-256μg/mL. As recommended by the NCCLS, we used 4μg/mL of 3 inhibitors. In the presence of clavulanate the MIC values of piperacillin against ESBL producers, TEM-33 and TEM-34 and Toho-type producers were 0.25-2μg/mL, 1-4μg/mL, 0.25-0.5μg/mL respectively. The MIC values of PIPC with sulbactam against ESBL producers, inhibitor resistant β-lactamases and Toho-typeβ-lactamases were 0.25-4μg/mL, 32-128μg/mL and 128μg/mL respectively. In the presence of tazobactam (TAZ) the MIC values were 0.25-4μg/mL, 4-8μg/mL and 1μg/mL for ESBL producers, inhibitor resistant β-lactamases and Toho-type β-lactamases respectively. These results suggest that β-lactamase inhibitors including TAZ show strong inhibitor activities against β-lactamase producing strains such as the ones mentioned in this article.

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