Metronidazole, like clindamycin, was active against a wide variety of anaerobic bacteria.Metronidazole was more active against 27 strains of B.fragilis (MIC₆₀;≤0.20μg/ml) than clindamycin (MIC₈₀;0.39μg/ml) and highly susceptible to clindamycin-resistant strains.
No cross resistance was found between metronidazole and clindarnycin.The antibacterial activity of metronidazole against 4 strains of C.difficile (MIC;≤0.2-0.39μg/ml) was almost the same as that of vancomycin.
Metronidazole in combination with cefoperazone or cefazolin synergistically inhibited the growth of the mixed cultures of 27 strains of B.fragilis and 1 strain of cefazolin-sensitive E.coil C-11 or 1 strain of cefazolin-resistant E.coli HI-54.

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In vitro combination effect of piperacillin (PIPC) and other β-lactams was investigated using gramnegative and gram-positive bacteria.
1. Disk approximation test using β-lactamase-producing strains such as Enterobacter cloacae H-27, Proteus vulgaris T-178, and Klebsiella ptutumoniae Y-4 revealed that more than half of 25 β-lactams tested showed antagonistic effect on PIPC against E.cloacae H-27 and P.vulgaris T-178 which produced an inducible β-lactamase.No interaction between PIPC and other β-lactams was observed against K.pneumoniae Y-4 which produced a constitutive penicillinase.
2. Five cephems i.c.cefazolin (CEZ), cefrnetazole (CMZ), cefoperazone (CPZ), cefbuperazone (CBPZ), and latamoxef (LMOX) were chosen for extensive examination of the combination effect with PIPC.
The combination of PIPC and CEZ or CMZ showed a marked antagonistic effect against 25 to 72% of Enterobacter species, Serratia marcescens, indole positive Proteus species, and Pseudomonas atmginosa which are species producing an inducible β-lactamase, while in this combination, synergistic effect was observed against a few of Escherichia coli, K.pneumoniae, P.mirabilis. The combination of PIPC and CBPZ, CPZ or LMOX hardly showed neither antagonistic nor synergistic effect against all the gram-negative species tested.
Synergistic effect against more than 30% of gram-positive cocci such as Streptococcus faecalis and Staphylococcus aureus which were methicillin sensitive strains was observed in the combination of PIPC and CMZ, CBPZ, or LMOX.Against 61 to 100% of methicillin resistant S.aureus, the combination of PIPC and the five cephems showed synergistic effect.
3. Both synergistic and antagonistic effect were confirmed by the growth curves using E.coli, S.aureus, and E.cloacae strains.
4. The extensive analysis of antagonism between PIPC and CMZ against E.cloacae GN 5797 showed that the inactivation of drugs by the induced β-lactamase might play an important role in the antagonism.

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Antimicrobial activity of 14 drugs against clinically isolated bacteria in Okinawa was examined. The activity of newly developed cephem except cefoperazone against Enterobacteriaceae and Haemophilus influenzae was excellent and unparalleled with the other drugs. Ceftizoxime was especially superior against Klebsiella as compared with the other cephem.
Gentamicin resistant strain (MIC≥12.5 μg/ml) was not found in Klebsiella, Serratia and Enterobacter. Without this phenomenon, drug sensitivity pattern of the clinical isolates was similar to that of the maon-land of Japan.
The addition of sulbactam (SBT) to cefoperazone (CPZ) was effective against the organisms in which MIC of CPZ was 12.5 μg/ml or more.But the MIC was not changed in 253 strains out of 455 in which the MIC was 6.25μg/ml or less, besides in 61 strains out of the 455, the MIC went up with the addition of SBT.

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The pharmacokinetic parameters of sisomicin (SISO) were studied in total 23 patients with normal renal function and with various degrees of renal impairment including patients under maintenance hemodialysis and continuous ambulatory peritoneal dialysis.In all cases 1 mg/kg of SISO was intra. venously administered with one hour constant infusion.
Serum concentration of SISO were determined by the high performance liquid chromatography method and pharmacokinetic parameters were obtained following the one-compartment model.The results were as follows:
1.In patients with normal renal function (mean creatinine clearance (Ccr): 98.0±26.1 ml/min), the mean peak concentration was 4.7±1.4μg/ml and the serum half-life (T_1/2) was 2.2±1.0hours.The apparent volume of distribution (V_d) was 10.1±5.5 1, i.e. 22.9±18.2%, of body weight.In case of renal impairment, the mean peak concentration was 4.1±1.4μg/ml in patients with Ccr of 45 to 69 ml/min and 4.9±2.1 μg/ml in patients with Ccr of 10 to 44 ml/min.T_1/2 was 2.1±0.7 hours and 12.4±6.8 hours, respectively.The volume of distribution (V_d) was 7.7±1.6 1, i.e.19.1±7.2% of body weight and 8.7±3.9 1, i.e.18.3±9.0% of body weight, respectively.
In patients under maintenance hemodialysis, the mean peak level and T_1/2 during interdialysis period were 4.5±1.5 μg/ml and 33.9±19.0 hours.V_d was 15.4±5.5 1, i.e.29.9±8.0% of body weight.
2. The renal insufficiency did not significantly affect the serum peak concentration and V_d However, plasma SISO concentration at two hours after the start of SISO infusion showed a significant correlation (r=0.750) with serum creatinine concentration.As shown in Fig.4, the correlation coefficient between plasma SISO concentration and serum creatinine concentration increased gradually, and reached to 0.843 at six hours.
3. When the SISO T_1/2 was compared with serum creatinine concentration, there was a good correlation (r=0.918 Y (T_1/2 in hours) =5.2×X (serum creatinine concentration in mg/dl)-2.8)(Fig.3).
4. For patients with impaired renal function, to obtain proper peak and trough concentration, only the prolongation of dosing intervals would be sufficient adjusting by the serum creatinine levels according to ZASKE's method.

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The concentration of CZX and CPZ were measured by high performance liquid chromatography (HPLC) after simultaneous intravenous administration of 1g of the agents.
The prostatic tissue and serum were obtained from 19 patients with benign prostatic hypertrophy, bladder cancer and prostatic cancer.
The prostatic tissue level of CZX was 25.4 μg/g in average and that of CPZ was 33.4 μg/g one hoar after the administration.
The prostatic tissue level of CPZ appeared to be higher than that of CZX, however prostatic tissue/serum concentration ratio of CZX was higher than that of CPZ.
Comparing their prostatic tissue levels with MIC₈₀ against pathogens from prostatitis, the clinical effectiveness of CZX and CPZ for prostatitis is expected.
The use of HPLC is very valuable to compare the antibiotic concentration of two different antimicro. bial agents in tissue and/or body fluid.

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Wound exudate was collected on every 30 or 60 minutes from 30 patients after radical mastectomy, to know how antibiotics penetrate into surgical wound.Ceftazidime (CAZ) and cefazolin (CEZ) were studied in this paper.The dose and route of administration were as follows (a) bolus injection of 1 g intravenously (1g IV), (b) bolus injection of 2g intravenously (2g IV), (c) drip infusion of 2 g for 60 minutes intravenously (2g DIV).
The peak concentration of CAZ was 39.7 μg/ml (1 g IV), 61.6 μg/ml (2g IV) and 51.8μg/ml (2g DIV).And that of CEZ was 19.1 μg/ml (1g IV), 64.7μg/ml (2g IV) and 44.0μg/ml (2g DIV). On time-concentration curve, each group needed 2-3 hours to reach the peak, and the concentration decreased slowly after the peak.So, the concentration of CAZ and CEZ was higher than 10μg/ml (1g IV) or 20 μg/ml (2g IV, 2g DIV) for 4-5 hours.That is, the more the dose of administration was, the higher the concentration of CAZ and CEZ in wound exudate was.On the route of administration, the peak concentration of bolus injection group was higher than those of drip infusion group (P<0.05).The concentration of drip infusion group reached the peak 30 or 60 minutes later than bolus injection group, but the decrease of concentration after the peak was similar in both group.
From above results, it was concidered that CAZ and CEZ penetrated well into wound exudate enough to prevent the breakout of infections after surgical operations.And it was suggested that bolus injection might be superior to drip infusion, as to the penetration of CAZ and CEZ into wound exudate.

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Nineteen patients with complicated urinary tract infections due to P.aensginosa were treated with combination of cefmenoxime and cefsulodin for 10 days and the clinical efficacies of 5 and 10 days chemotherapy were compared.
Overall clinical efficacies of 10 days chemotherapy were slightly higher than those of 5 days chemotherapy. This was mainly due to improvement in the rate of excellent response and no difference was observed in the rate of excellent plus moderate response.Eradication rate of P.aeruginosa showed no significant difference between the 5 and 10 days chemotherapy.From the results obtained, initial chemotherapy of 5 days duration was regarded as sufficient for the evaluation of drug efficacy even for complicated urinary tract infections due to P.aeruginosa.
Changes of pyuria and bacteriuria during the follow-up period of 3 to 31 days (average 9.7 days) after initial chemotherapy with combination of cefmenoxime and cefsulodin for 5 or 10 days were studied in 23 patients with complicated urinary tract infections due to P.aeruginosa whose bacteriuria were eliminated by initial chemotherapy.
Pyuria were aggravated in 34.8% and bacteriuria in 65.2% of the cases. Of the 15 patients with aggravation of bacteriuria, 13 patients were due to P.aeruginosa and these aggravations were regarded as relapse from the results of sero-cype and phage-type determination.
Suppression of relapse by maintenance chemotherapy after successful initial chemotherapy was considered as important in the treatment of complicated urinary tract infections due to P.aerugisota. Further clinical studies are expected to clarify the indication, duration and the limitation of maintenance chemotherapy.

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