The present in vitro antibacterial activity of five third-generation cephalosporins (cefotaxime, latamoxef, cefmenoxime, cefpiramide, cefoperazone), four first- and secondgeneration agents (cefazolin, cefotiam, cefmetazole, cefamandole) and eight other antimicrobial agents were simultaneously compared against 384 strains of Gram-positive cocci, 595 strains of Enterobacteriaceae, 240 strains of non-fermenters and 143 strains of anaerobin bacteria and others. The agar dilution method was used to measure the minimum inhibitory concentration (MIC) and the results were expressed as MIC range, MIC_50% and Among β-lactams, cefotaxime and latamoxef exhibited the highest activity against a wide variety of Gram-positive and Gram-negative bacteria. Cefpiramide and cefoperazone were generally less active than these two agents, although cefpiramide showed good activity against P. aeruginosa strains. Ofloxacin, a new pyridone carboxylic said derivative, inhibited the growth of over 80% of strains in all species tested, except C. difficile strains, at a concentration of 3. 13 μg/ml. All the strains were tested for β-lactamase production by the Cefinase disc method and susceptibility to β-lactams evaluated in each of the species. We hope to have demonstrated the need for periodic susceptibility testing to provide guidance for empiric chemotherapy.

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The sensitivity to chemotherapeutic agents of 200 isolates of Staphylococcus aureus, isolated in seven institutions in the northeast of Japan, was examined by the microbroth dilution method using the Dynatech MIC-2000. Also, β-lactamase activity was semi-quantitatively determined by disk acidmetry. In this study, we investigated a total of 24 chemotherapeutic agents: five penicillins (ampicilfin, amoxicillin, . piperacillin, methicillin and cloxacillin), eight cephems (cefazolin, cefotiam, cefamandole, cefmetazole, ceftizoxime, cefoperazone, ceftazidime and latamoxef [moxalactamp]), three aminoglycosides (gentamicin, dibekacin and amikacin), a tetracycline (minocycline), two new-quinolones (norfloxacin and ofloxacin), and others including clindamycin, rifampicin, vancomycin, fusidic acid and fosfomycin.
The incidence of methicillin-resistant (MIC≥12.5μg/ml) strains of S. aureus was 25.5%(51/200), and that of cefazolin-resistant (MIC≥12.5μg/ml) strains was 21.0%(42/200) respectively. The in cidence of MRSA was found to vary from 0%-40%, and the difference was statistically significant. Also, the incidence of MRSA in strains recovered from pus was significantly higher than from other specimens such as sputum, otorrhea, urine and blood. Out of a total of 200 strains, 171 were found to produce penicillinase. The incidence of the penicillinase-positive strains, especially those which show moderate or strong activity, was statistically higher in MRSA than in MSSA (methicillinsensitive S. aureus) and statistically significant (P<0.01). The recovery of sensitivity to methicillin after 20 hr incubation at 44°C was demonstrated in 30% of MRSA. Based on our findings, we suggest that the mechanism of resistance in MRSA is in greater part related to β-lactamase activity. Almost all of the MRSA were sensitive to cloxacillin, amikacin, cefamandole, cefmetazole, minocycline, rifampicin, ofloxacin, norfloxacin, vancomycin and fusidic acid.

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A radioisotopic method was used to determine the penetration of five macrolide antibiotics into human polymorphonuclear leukocytes (PMN). The penetration ratios (that is, of the cellular concentration to the extracellular concentration) of erythromycin, josamycin, rokitamycin, TE-031, and Ru-28965, all macrolides, were very high. Macrolide uptake by PMN was dependent on environmental temperature and cell viability. Also, the accumulation of these antimicrobials was inhibited by sodium cyanide, potassium fluoride, and adenosine. Based on our findings, we consider that macrolide uptake by human PMN is mediated by an active transport system, and more specifically a nucleoside transport system.

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To investigate the usefulness of ceftixoxime (Epoceline^®, CZX) a cephalosporin antibiotic, on the mandibular tissues, serum and tissue concentrations of the drug were measured by bioassay in 11 patients with progenia undergoing the mandibular body ostectomy.
The following results were obtained.
1. Concentrations of CZX in serum and in the mandibular tissues after 2.0g i. v. injection were measured. Serum concentrations were expressed with the following equation: C=120.2e^-0.713t.Half-life was 0.97 hours. Concentrations in the mandibular tissues were C=11.8e^-0.672t. Half-life was 1.03 hours.
2. The ratio of mandibular tissue to serum concentrations was about one-tenth 30-180 minutes after intravenous injection.
3. Concentrations of CZX in serum and the mandibular tissues exceeded its MIC. against the stab causative organisms. We therefore conclude that CZX is useful in the treatment of various infections in the field of oral surgery and for the prevention of postoperative infections.

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Cefmenoxime concentrations in blister fluid induced by suction were determined in 12 adult burn patients after an intravenous bolus injection (50 mg/kg body weight) of the drug. The cefmenoxime concentration in the suction blister fluid reached its maximum level (25.8μg/ml) at 1 hr. Using a two-compartment open model, C_max (maximum concentration), T_max (time of maximum concentration) and apparent transport ratio (F) (k1·Vs/k2·Ve) were calculated as 26.6 μg/ml, 2.14 hr, and 0.54, respectively.
We compared the data with those on exudates from excoriated skin wounds and burn wounds, and with the data on burn blister fluids given in our previous paper. The pharmacokinetic parameters of cefmenoxime concentrations in suction blister fluids resembled those in burn blister fluids of been patients. It appears from this study, that suction blister fluids are a useful model for burn blister fluid.

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The diffusion of imipenem (MK-0787) and cilastatin sodium (MK-0791) into prostatic tissue after intravenous administration of imipenem/cilastatin sodium (500 mg/500 mg) in patients with benign prostatic hyperplasia was studied.
The concentrations in prostatic tissue and the ratio of prostatic tissue levels to plasma levels one hour after administration were 3.2±0.6μg/g and 0.25±0.08 for imipenem and 8.4±1.01μg/g and 1.00± 0.12 for cilastatin sodium.
The diffusion of imipenem into prostatic tissue was not particularly good, but its concentration exceeded the values of MIC₈₀ against almost all organisms isolated from urinary tract infections, including P. aeruginosa, S. marcescens and E. faecalis.

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To verify the effect of ambroxol, an expectorant, which increases the amount of antibacterial agent in sputum, we measured the concentration of IgG, secretory IgA and lysozyme in sputum by laser nephelometry in 11 patients with chronic respiratory tract infection before and after administration of ambroxol. On average, the sputum volume increased from 31.5 ml to 34.7 ml, IgG from 12.9mg to 16.5 mg and lysozyme from 0.68 mg to 1.47 mg. The elevation of these parameters was noted in 10 out of 11 patients (91%) and 6 out of 11 patients (55%). The mean amount of secretory IgA in sputum did not increase after administration of ambroxol, though secretory IgA increased in 4 out of 11 patients (36%). The increase in IgG was greater than that in sputum or albumin.
These results suggest that ambroxol promotes penetration of IgG into sputum from blood, stimulates the production of IgG in the lungs and enhances the secretory function of the bronchial glands. On the basis of our findings, we further suggest that ambroxol, by increasing the amount of antibacterial agent in sputum, reinforces the defensive function of the airways against infection, and is clinically significant in combination with chemotherapy.

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Fifty-two women with acute uncomplicated cystitis were treated with a single 400 mg oral dose of enoxacin. This regimen effectively eradicated the original organisms in all the patients treated.
Clinical efficacy was evaluated, based on the parameters of urine culture, pyuria and subjective symptoms. Forty-five cases were evaluated as excellent, 6 as good and 1 as failed. In this last case, the infecting organism was resistant to enoxacin.
Relapse, beginning 7 to 10 days after treatment, was noted in 2 out of 28 patients, whose initial infection had been eradicated.
No untoward reactions were encountered.

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