The purpose of this study was to examine the fractional inhibitory concentration (FTC) index of β-lactams and aminoglycosides (AGs) against S. marcescens. The correlation between growth curves and morphological changes in the bacteria was also clarified at sub-MIC levels.
In vitroactivities of 27 kinds of combination of 10 β-lactams and 4 AGs against 27 strains of S. marcescens isolated from patients with urinary tract infections and S. marcescens strain IFO12648 were studied using the checkerboard method.
Combination of so-called third-generation cephems (CEPs) and AGs seemed to enhance the bactericidal effect against almost all strains tested. Growth curves of these strains and the standard strain were studied after addition of each drug at sub-MIC level. The initial inoculum size was 10⁴-10⁵CFU/ml.
Scanning electron microscopic (SEM) observations were also performed.
Synergistic inhibitory rates and minimum FIC indices were: LMOX 89%(0.241), CZX 74%(0.322), CPZ 82%(0.310). all in combination with GM; and LMOX 74%(0.359), CZX 78%(0.385) and CPZ 63%(0.384) with AMK.
A bactericidal effect of LMOX with GM against S. mercescens No.10 strain (minimum FIC index; 0.125) was observed after adding 1/2 and 1/4 MIC, respectively. After incubation with 1/8 and 1/16 MIC, respectively, for 8 hours, viable bacteria decreased to 1/10 to 1/100 of the controls. With each 1/16 MIC of CZX and GM (minimum FIC index; 0.065) the standard strall was suppressed to 1/100 to 1/1, 000 of the controls 8 hours later.
SEM demonstrated prominent bacteriolysis and/or filament formation after combination of sub-MICs in comparison with a single regimen.
Although the minimum FIC indices did not always coincide with antibacterial synergism, growth. curve tests always reflected morphological changes as far as sub-MIC combinations of the thirdgeneration CEPs and AGs were concerned.

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Imipenem/cilastatin sodium was administered to 9 patients with pleural effusion to observe the time-course of distribution of the drug into plasma and pleural effusion. The following results were obtained.
1) Both imipenem and cilastatin sodium levels reached a peak in the plasma at the end of drip infusion of the drug and then gradually decreased, while in the pleural effusion, imipenem reached a peak 1 hour and cilastatin sodium 2 hours after the infusion. The average peak imipenem level in the pleural effusion was 3.8μg/ml in the 250mg/250mg administration group, and 5.5μg/ml in the 500mg/500mg administration group. The peak cilastatin sodium level was 3.5μg/ml (250mg/250mg), and 4.9 μg/ml (500mg/500mg).
2) The ratio of peak imipenem levels in plasma and pleural effusion was 22.1% in the 250mg/250mg administration group and 22.4% in the 500mg/500mg administration group. The ratio of peak cilastatin sodium levels in plasma and pleural effusion was 14.6%(250mg/250mg) and 14.8%(500mg/500mg).
We consider that the penetration of both imipenem and cilastatin sodium into pleural effusion is good.

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Antibacterial activities of sulfamethoxazole-trimethoprim (ST), minocycline (MINO), doxycycline (DOXY), erythromycin (EM), 9-3''-diacetyl-midecamycin (MOM), cefaclor (CCL), T-2525, enoxacin (ENX), and ciprofloxacin (CPFX) against E. coli, K. pneumonias, P. mirabilis and E. faecalis were studied under a variety of pH conditions.
Whereas the antibacterial activity of EM was markedly enhanced with alkalinisation, those of MINO and DOXY were decreased. Those of the other drugs were unchanged or slightly decreased with snap linization.
Since prostatic fluid in human chronic bacterial prostatitis is alkaline, we suggest that the clinical value of EM (whose antibacterial activity is enhanced with alkalinization), ENX and CPFX in this condition should be investigated.

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We compared the safety and efficacy of moxalactam (LMOX), a third-generation cephalosporin, to cefmetazole (CMZ), a second-generation cephalosporin, as prophylactics in patients undergoing elective colorectal surgery.
One hundred and fifty-four patients were randomized for therapy with either LMOX or CMZ at a dose of 2g i. v. immediately before surgery and thereafter 1g 8-hourly for 4 days. Seventyseven patients were given LMOX and the same number CMZ. Both groups were comparable in age, sex, type of intervention and diagnosis. Two patients were excluded from each group because of postoperative noninflammatory complication. The incidence of surgery-related postoperative infection differed significantly between the LMOX group (n=75) and the CMZ group (n=75). There was only one intraabdominal abscess in the LMOX group, but nine wound infections and one intraabdominal abscess in the CMZ group. No C.difficile toxin was found in the patient with diarrhea. In the early postoperative period, abnormal liver function was noted in 19 patients in the LMOX group and in 10 patients in the CMZ group. The ratio of side-effects and abnormal laboratory findings did not differ significantly between the groups.
Our conclusion, based on the results of this study, is that LMOX is a more effective prophylactic antibiotic than CMZ in patients undergoing elective colorectal surgery.

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We conducted pharmacokinetic studies on anticancer drugs under angiotensin II (AT-II)-induced hypertension chemotherapy (IHC). AT-II was administered to Sarcoma 130-bearing mice at 1-2μg/kg/min for 5 min to elevate the blood pressure, then 40mg/kg of 5-fiuorouracil (5-FU) or 10mg/kg of adriamyein (DXR) was administered intravenously and additional AT-II was infused into the tail vein for 10 min.
Results: 1. The level of anticancer drugs in the tumor tissue correlated negatively with the weight of the tumor, suggesting that the anticancer drugs penetrate very little into the deep region of solid tumors.
2. A larger quantity of the anticancer drugs was delivered selectively into the tumor tissue by IHC.
3. The increase of the area under the concentration curve (AUC) for 5-FU under IHC was greater in larger tumors when compared.
4. A lower efflux of the anticancer drug from the tumor tissue was observed in larger tumors under IHC.
5. The pharmacokinetics of 5-FU and DXR under IHC differed each other in detail.

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