In studying the relationship between pharmacokinetic variables for serum vancomycin (VCM) and therapeutic outcome, we analyzed data from 31 patients with pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). VCM was effective in 21. Comparing pharmacokinetic variables between the 21 responders and 10 nonresponders yielded the following median (interquartile range) within 1-2 hours after VCM administration was stopped: Cmax, 37.1μg/mL (29.9-42) vs. 32.3μg/mL (29.5-36.1)(P=0.32); trough, 10.5μg/mL (8-12.4) vs. 8.7μg/mL (6.7-11.2)(P=0.25); elimination constant (Ke), 0.17/h (0.10-0.22) vs. 0.15 hr (0.11-0.17)(P=0.67); and area-under-the-concentration curve (AUC), 410μg·h/mL (349-455) vs. 318μg/mL hr (302-328)(P<0.01). AUC was the only statistically significant pharmacokinetic variable. Receiver operating characteristic curve analysis showed AUC cutoff of 330μg/mL · hr (sensitivity, 76.2%; specificity, 80.0%). AUC distribution for the 21 responders and MIC distribution for VCM of 373 MRSA strains isolated at Tenri Hospital were integrated over 1, 000 Monte Carlo simulation trials. The probability of attaining an AUC/MIC of 330 was 56.8%. These results indicate that AUC reflected VCM clinical efficacy for MRSA pneumonia, and the AUC cutoff was 330μg/mL·hr. Monte Carlo simulation also indicated a low probability of attaining an AUC MIC ratio 330. We therefore suggest that the AUC/MIC ratio be adopted as an index for VCM treatment.

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We studied dose regimens of cefepime (CFPM) in patients with renal impairment using population pharmacokinetic (PPK) modeling. PPK analysis incorporated body weight (BW) and creatinine clearance (Ccr) as covariates and was used to predict serum concentration-time profiles and pharmacokinetic (PK) parameters after 30-minute intravenous infusion at 0.5-2g of CFPM once (QD) or twice (BID) a day in patients with Ccr from 5 to 50mL/min and BW between 40kg and 90kg. For late-stage renal failure patients undergoing hemodialysis, PK profiles of CFPM after a 1g loading dose followed by 0.5g QD dose were estimated in patients with Ccr of 5mL min by a PPK model modified with hemodialysis clearance. Hemodialysis was modeled as three times a week just before CFPM 0.5g QD administration. T>MIC was used as the pharmacokinetic/pharmacodynamic (PK/PD) index and calculated using MIC₉₀ for Pseudomonas aeruginosa. Compared to the PK profile predicted at 2g BID for patient with normal renal function, results suggest the following:
1. For patients with renal impairment managed without hemodialysis, CFPM 2 g BID for Ccr>50mL/min, 0.5-1g BID for Ccr 10-50mL min, and 0.5-1g QD for Ccr<10mL, minshow sufficient T>MIC₉₀ that predict clinical effects without excessive accumulation.
2. For patients with renal impairment managed with hemodialysis modeled as three times a week, CFPM 1g loading dose followed by 0.5g QD dose just after hemodialysis avoids marked T>mIC90 decrease and reaches sufficient T>MIC₉₀ while hemodialysis removes CFPM from blood and rapidly decreases serum concentrations.
3. No dose adjustment in BW from 40 to 90kg is required for patients with renal impairment managed with or without hemodialysis since no remarkable changes in PK profiles and T>MIC. were estimated within the BW range.

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We report typhoid fever showing reduced susceptibility to fluoroquinolones treated successfully with tosufloxacin (TFLX) combined with cefotaxime (CTX). A 21-year-old Japanese man visited India and Nepal between June 10 and September 7, 2004, developed a high fever and diarrhea on August 30 while in Nepal. After returning to Japan and being seen elsewhere, he was transferred to our department. Laboratory findings on admission included thrornbocytepenia and elevated serum transaminase, but no Plasmodium spp. in blood smears. Salmonella Typhi was isolated from blood cultures, and the patient was diagnosed with typhoid fever. TFLX 300mg b. i. d. was administered, but the fever persisted. The S. Typhi strain isolated from the patient was resistant to nalidixic acid in vitro, so we added of CTX 4g/day i. v. to TFLX, resulting in good combined effect. The minimum inhibitory concentrations (MIC) of TFLX, CTX, and NA for S. Typhi thus isolated were 0.25μg/mL, 0.5μg/mL, and 256μg/mL. By calculating the fractional inhibitory concentration (FIC) index based on a checkerboad technique, we demonstrated in vitro synergism of TFLX with CTX. Combining of TFLX with CTX is thus expected to effectively treat typhoid fever with reduced susceptibility to fluoroquinolones.

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We conducted a drug use investigation of azithromycin -Zithromac^® Tablets 250mg, Zithromac Fine Granules for Pediatric Use, and Zithromac ^® Capsules for Pediatric Use 100 mg for 3 years from 2000. We collected reports on 4, 622 cases from 278 medical institutions nationwide and evaluated safety and efficacy of azithromycin in 3, 745 cases subject to safety analysis and 3, 126 cases subject to efficacy analysis.
The incidence of adverse reactions was 2.40%(90 /3, 745). Major adverse reactions included 30 cases of diarrhea, 15 of vomiting, 11 of increased alanine aminotransferase (ALT), 7 of increased aspartate aminotransferase (AST), and 6 of nausea.
Efficacy by to indication was 82.0%(418/510) for adult dermatological infection, 82.0%(858/1, 046) for adult respiratory tract infection, 80.0%(92/115) for adult sinusitis, 89.4%(320 358) for adult dental /oral infection, 80.8%(813/1, 006) for pediatric respiratory tract infection, and 69.2%(63/91) for pediatric otitis media.
Compliance by dosage form-patients who took the drug following the instruction provided-was 97.5%(2, 312/2, 372) for tablets, 93.5%(1, 128/1, 206) for fine granules, and 97.1%(133/137) for capsules.
Results were favorable for safety, efficacy, and compliance.

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