Antibiotics abuse causes drug resistance.Between 2001 and 2004, we conducted several trials to evaluate the effectiveness of measures to inhibit antibiotic use. From September 2001, we required physicians treating patients with anti-MRSA agents, and from November 2003, those treating patients with carbapenems, to report the reason for their choice of antibiotics to an Infection Control Committee prior to administration to patients (reason-report). From October 2003, physicians with patients suffering from bacteremia were supported by infection control physicians (Guidance by ICD). In addition to the interventions above, from April 2004, through therapeutic drug monitoring (TDM), physicians prescribing drugs for all patients with MRSA received advice from pharmacists on optimal dosage. We studied the effects of these interventions on the prescription of carbapenems and anti-MRSA agents.
Combined, TDM and the other two interventions significantly reduced daily doses of vancomycin. Guidance by ICD decreased the number of patient prescribed anti-MRSA agents. Taking reason-report and guidance by ICD together raised the daily dose of panipenem/betamipron (0.5g/V) significantly.
In conclusion, we found that presentation of a report detailing reasons for prescription is ineffective in limiting the amount of anti-MRSA agents prescribed, but both TDM and guidance by an infection control physician effectively reduced prescribed amounts. We consider that administration criteria of carbapenems are necessary.

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MRSA infection poses a great problem in neonatal intensive care units (NICU).Pharmacokinetics and optimum dosage of arbekacin sulfate (ABK), an anti-MRSA agent, have not yet been fully investigated in neonates. We retrospectively analyzed the serum concentration of ABK in 41 neonates treated with ABK based in the Ministry of Health and Welfare, Japan, approved dosage (pediatric dosage) at our NICU to assess population pharmacokinetic parameters.The initial dosage was set based on the means of population pharmacokinetic parameters using a nonlinear mixed effects model (NONMEM).The dosage and dosage interval were set to produce a trough of ≤ 2mg/L and a peak of ≥ 7mg/L. Because of a rapid change in clearance around the postconceptional age (PCA) of 33 weeks, initial dosages were set between PCA of 28 and 37 weeks (±30% of the clearance at PCA of 33 weeks): 4mg/kg×1/48 hr at<28 weeks, 3mg/kg×1/24hr between 28≤weeks and <33weeks, 4mg/kg×1/24hr between 33≤ and <37 weeks, and 7mg/kg×1/24hr at 37≤weeks.The dosage was reassessed in 19 neonates who received the initial dosages given above.The regimen given in the pediatric dosage peak and trough [10.3±5.6 (3.5-22.2) and 6.0±4.7 (0.4-17.6) mg/L]. Our regimen satisfactorily controlled blood concentration [mean trough and peak values: 1.6±0.8 (0.4-3.2) and 9.0±2.2 (5.6-13.3) mg/L]. Twice-a-day administration of ABK in neonates resulted in anaccumulation in the trough, indicating the efficacy of early dosage with a 24 to 48 hour interval.

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Between July 2005 and September 2005, we enrolled 129 children with group A streptococcal infection in a prospective multicenter study. Children aged from 6 months to 15 years (52±2.4years) treated with cefcapene pivoxil 9mg/kg/day tid for 7 days were evaluated for clinical efficacy and bacterial effect at the end of therapy and were observed for the occurrence of recurrent infection and complications 4 weeks after the end of therapy.The most frequent T-types of 129 isolates were T12, T4, and T1 at 40.3%, 27.1%, and 9.3%.
Of the 129, 3 refused to take the drug and 14 did not return for follow-up. The 112 we evaluated experienced clinical efficacy and their symptoms were ameliorated. Six still had GAS from pharyngeal swabs at the end of therapy. Isolates from 5 were identical to initial strains in T-type and PFGE pattern.
All 108 observed within 1 month after the end of administration had no complications, but 7 had a recurrence of GAS infection. Four still had GAS from pharyngeal swabs at the end of therapy and isolates from one differed from initial strains in T-type and PFGE pattern.Adverse effects were diarrhea observed in 3 and vomiting in 1.

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We report a case of anaphylactic shock treated based on a clinical guideline for anaphylactic reaction asso. ciated with antibiotics under general anesthesia.
A 63-year-old woman scheduled to undergo an excision of perianal Bowen's disease and a colostomy was given cefmetazole intravenously after induction of general anesthesia. Five minutes later, her systolic blood pressure decreased to 53 mmHg and erythema and edema appeared on her face and palms. Treatment based on the guideline was started immediately. She recovered from severe shock. Although the guideline is useful even in general anesthesia, it is important for anesthesiologists to interview patients regarding allergenic history, to observe skin symptoms carefully during administration, and to treat shock immediately.

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In clinical practice, we frequently see patients with metastatic cancer in which the primary site remains unknown. We combined chemotherapy consisting of paclitaxel (TXL) and carboplatin (CBDCA) in four patients with primary cancer of unknown origin: 2 men and 2 women, median age of 58 years.histopathologically diagnosed with adenocarcinoma.TXL (200mg/m², day 1) and CBDCA (target AUC: 6mg/mL/min, day 1) were given every 3 weeks.We observed a partial response (PR) in 1 patient, stable disease (SD) in 2, and an unevaluable in 1.The PR patient remains alive 2 years after therapy.One SD patient survived 20 months, and the nonevaluable patient 2 months.The second patient with SD was not followed beyond 15 months after chemotherapy completion.
CBDCA-based combination chemotherapy is recommended for treating of primary cancer of unknown origin. Despite some success, much room remains for improvement.Further clinical trials are essential to achieve better survival and a more favorable prognosis for these patients.

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