Cefuroxime is a new cephalosporin antibiotic with increased stability to 8-lactamse. This stability has the effect of widening the antibacterial spectrum of the compounds so that Cefuroxime is active also against cephalosporin resistant strains such as E. coli and Klebsiella, Proteus, Enterobacter and Citrobacter. This characteristic of Cefuroxime is expected to be useful for the treatment of urinary tract infections.
In order to study the efficacy, safety and usefulness of Cefuroxime for the treatment of urinary tract infections, a comparative study was carried out by the double blind method, using Cefazolin as the control drug.
The subjects of this study were in-patients with urinary tract infections excluding those with acute simple-cystitis, aged 15 years or older. Both antibiotics were given in doses of 750 mg i. v. three times daily for five consecutive days.
Of 227 cases recruited in this trial, 160 were judged as appropriate for the assessment of the clinical efficacy by the Committee members, and 166, by doctors in charge.
The background factors of the patients in the CefLroxime treated group and Cefazolin treated group were almost the same.
The overall clinical efficacy of Cefuroxime in all patients was significantly superior to that of Cefazolin in both the judgements by the Committee members (Cefuroxime: 79%, Cefazolin: 61%) and by doctors in charge (Cefuroxime: 75%, Cefazolin: 58%).
Especially, Cefuroxime was significantly superior to Cefazolin for the treatment of patients with complicated infections, chronic infections and infections of organisms inapplicable to Cefazolin and those showing not less than 200 genii in minimum inhibitory concentration of each antibiotic treated.
Side effects and changes in laboratory values attributable to medication were noted in 8 of 113 in Cefuroxime treated group and in 9 of 114 Cefazolin treated group.
Cefuroxime showed a tendency to be superior to Cefazolin in its usefulness in the judgement by doctors in charge.
From the above results, it has been confirmed that Cefuroxime is a useful antibiotic for the treatment of urinary tract infecticns.

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A dose-response study on therapeutic effect of miloxacin (MLX) on acute simple cystitis in women was performed by a double-blind method.
(1) Overall clinical efficacy (effective rate) was 89.2. 81.8, 74.4 and 42.1% in groups administered 1, 000, 500, 250 and 125 mg/day (q. i. d.) of MLX, respectively. When compared among the cases caused by gram-negative rods, the group administered 1, 000 mg/day of MLX showed a significantly higher overall clinical efficacy than other three groups. It was, therefore, assumed that the appropriate dosage of MLX for clinical use was 1, 000 mg/day.
(2) After the oral administration of MLX at the doses of 250, 125, 62.5 and 31.25 mg, the mean concentrations of the drug in urine (urine volume was corrected to 1 ml/min) ranged 12.6-23.8, 3.5-8.4, 3.1-5.7 and 0.8-2.3μg/ml, repectively. A curve was prepared by plotting the drug concentration in urine against the efficacy on bacteriuria at each dosage group. It was found that this curve was similar to the cumulative MIC curve against the bacteria isolated from urine of the patients of this study. When the MIC cumulative curve was shifted to the higher concentration by two tubes, these two lines fitted each other almost well. In other words, it was indicated that, multiplying the MIC values by a certain coefficiency, the cumulative MIC curve against urinary isolates was coincided with the curve obtained by plotting the drug concentration in urine against the effective rate.

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The pharmacokinetics of cefroxadine (CXD, CGP-9000), a new oral cephalosporin antibiotic, were characterized in 5 healthy volunteers and 10 patients with different endogeneous creatinine clearances (Ccr) on the basis of a one-compartment open model. Each subject received a single 500 mg oral dose of CXD, and serum and urinary concentrations of the antibiotic were measured by bioassay. The mean peak concentration of CXD (11.6μg/ml) was achieved 2 hours after administration in normal subjects. The mean serum half-life was calculated for 58 minutes in normal subjects, and increased in patients along with increasing impairment of renal function. A significant correlation between the elimination rate constant and Ccr was demonstrated. In normal subjects, 63 to 97 per cent of administered dose was excreted in the urine within the first 6 hours while the urinary excretion rate declined gradually in patients as a degree of renal impairment advanced.

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To study the penetration of antibiotics into interstitial fluid, granuloma pouch model induced by either 1% croton oil or 1.5mg of Mycobacterium tuberculosis Aoyama B in the back of rat was applied. Pouches were filled with inflammatory exudate (4 days, 3-7ml; 6-43 days, 8-20 ml) having a protein concentration range of 3.5-4.5g/100ml. Exudate antibiotic levels after intravenous ijection depended upon the doses and the serum binding rates but not the inflammatory process. Furthermore, an intravenous injection of antibiotics developed greater exudate level than an intramuscular injection. These results indicate that antibiotic concentration in exudate was reflected by the protein-free concen. tration in serum. Therefore, this granuloma pouch model appears to be useful for measurement of interstitial antibiotic levels in rats.

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In vitro combined action of Minocycline with Dibekacin or with Sulbenicillin against 86 clinical isolates of Gram-negative bacilli was examined by checkerboard technique and by analysis of the effects on the growth curves.
The combinations of Minocycline with Dibekacin and Minocycline with Sulbenicillin, showed an apparent synergistic antimicrobial action against patient strains of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae.
Generally, an increase in antimicrobial activity of Sulbenicillin was observed when it was combined with Minocycline, although on rare occasion a slightly antagonistic effect was seen in small number of strains tested.
The combination of Minocycline with Dibekacin was shown to be antagonistic against patient strains of Serratia species, while the combination of Minocycline with Sulbenicillin showed a marked synergistic activity against these strains.
Anti-pseudomonas activity of Minocycline became intensified when it was combined with either of the two agents, Dibekacin or Sulbenicillin.
The combination of Minocycline and Sulbenicillin revealed to be synergistic against patients strains of Acinetobacter calcoaceticus among glucose-nonfermentative gram-negative bacilli.
As a rule, in the strains, against which the combination was shown to be synergistic by checkerboard technique, the synergistic effect was similarly observed on the growth in liquid medium.
In contrast, in the strains in which an antagonistic action was demonstrated by the checkerboard. technique, an antagonistic effect on the growth curves was rarely shown, and even a slightly synergistic action was observed in a portion of the strains.

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The susceptibility testing of 86 strains of Mycobacterium intracellulare, comprising 49 strains of human isolate, 21 of swine isolate and 16 of environmental isolate, to 10 kinds of anti-tuberculous drugs was performed, using ring diffusion method (HIRAMINE, S.: J. Med. Technol., 15: 271-273, 1971). M. tuberculosis H 37 Rv strain served as the control.
Susceptibility to the first choice anti-tuberculous drugs: The minimal inhibitory concentration (MIC) of SM, PAS and INH against 86 strains of M. intracellulare were: SM, 20μg/ml to 45 strains, 200 μg/ml to 38 strains, namely 200μg/ml or less to 83 strains (97%) in total; PAS, 10μg/ml or less to 2 strains (2%): INH, 5μg/ml or less to 19 strains (22%). The SM, PAS and INH completely inhibited the growth of H 37 Rv strain of M. tuberculosis at MIC of 20, 1 and 0.1 μg/ml, respectively.
Susceptibility to the second choice anti-tuberculous drugs: All the drugs tested completely inhibited the growth of H 37 Rv strain of M. tuberculosis at MIC: KM, 25μg/ml; CS, 20μg/ml; TH, 25μg/ml; EB, 2.5μg/ml; VM, 25μg/ml; CPM, 25μg/ml; and RFP, 10μg/ml. The M. intracellulare strains inhibited to grow completely at the concentration noted above were few as follows, with the exception of 66 strains (77%) to RFP: KM, 24 strains; CS, 3 strains; TH, 2 strains; EB, 3 strains; VM, 5 strains; and CPM, 1 strain. A consideradle number of strains were barely inhibited to grow at the high concentration: KM, 100 μg/ml to 53 strains (62%), 1000μg/ml to 8 strains (9%), namely 61 strains (71%) in total; CS, 40μg/ml to 59 strains (69%); VM, 100μg/ml to 51 strains (59%); CPM, 100μg/ml to 61 strains (71%). In the case of TH and EB, however, susceptible strains were limited as follows: TH, 50 μg/ml to 17 strains (20%); EB, 5μg/ml to 13 strains (15%). The cumulative numbers of susceptible strains at the maximal inhibitory concentrations tested were as follows: KM, 1, 000 μg/ml or less, 85 strains (99%); Cs, 40 genii or less, 62 strains (72%); TH, 50μg/ml or less, 19 strains (22%); EB, 5μg/ml or less, 16 strains (19%); VM, 100μg/ml or less, 56 strains (65%); CPM, 100 μg/ml or less, 62 strains (72%); and RFP, 50μg/ml or less, 83 strains (97%).
It is concluded that many strains of M. intracelluare were sensitive to RFP, whereas few strains were susceptible to SM, KM, CS, VM, and CPM. However, the susceptibility of this bacterium to anti-tuberculous drugs was generally lower than that of M. tuberculosis. These findings nearly coincided with those of previous investigators who used the routine dilution method.

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