Prothrombin time (PT) and partial thromboplastine time (PTT) were analysed retrospectively in 62 patients with respiratory infections treated with antibiotics through 1977 to 1979, and three other cases receiving hemodialysis were also observed on their cascade of coagulation after intravenous administration of carbenicillin (CBPC). Although slight abnormality of coagulant activity was observed in some cases after treatment with oral antibiotics, no relationship was found between the abnormality and the doses of antibiotics.
On the other hand, distinct prolongation of both PT and PTT was observed within one to two weeks in some of the cases receiving intramuscular (i. m.) or intravenous (i. v.) injection of antibiotics, PT and PTT of these cases recovered to normal range after discontinuation of the antibiotics.
Although severe prolongation of PT and PTT was observed in two of the renal failure cases after single dose of 5g CBPC, no treatment was needed for that.
None of the cases showed clinical symptoms and signs of blood coagulopathy. However, the influence of antibiotics on the coagulation cascade, sometimes found as abnormal changes of PT or PTT, especially in patients receiving i. m. or i. v. antibiotic administration, calls our attention to the blood coagulability of the patients during antibiotic therapy.

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Nine-hundred and forty-two isolates of coagulase-negative staphylococci from patients in ten hospitals and ninety-three isolates of coagulase-negative staphylococci from the fingers of surgical personnel were examined. All of them were identified by the computer program of biochemical typing based on probability matrices which were developed from the test results of about 1, 000 strains identified by the methods of KLOOS and SCHLEIFER. One-third of the identified isolates were phagetyped with the sets of PULVERER and de SAXE and were investigated on antibiotic susceptibility by the official method of Japan Society of Chemotherapy. In the results of identification, four-hundred and fortythree strains (42.8%) are S. epidermidis. Judging from the results of phage-typing, the typabilities by the two sets are unsatisfactory and it should be desired to develop the new typing set more adequate for the national strains. In minimum inhibitory concentrations (MICs) for ten antibiotics and distributions of them, the strains with high MICs are observed much more in the clinical isolates than in the isolates from fingers. This tendency is obvious especially in the MICs for gentamicin, which is clinically so important fact due to the frequent use of gentamicin. In the susceptibility of three-hundred and eighty-seven clinical isolates to novobiocin six out of nine S. saprophyticus, four out of six S. xylosus and six out of eleven S. cohnii have MICs of less than 1.6μg/ml, while forty-six out of two-hundred and ten S. epidermidis have MICs of not less than 1.6μg/ml. These results point out that, as KLOOS and SCHLEIFER mentioned, susceptibility for novobiocin could be variable with exposure to it in environment. Therefore, it can be said that this kind of antibiotic is inadequate to be employed for identification of strains. Coagulase-negative staphylococci could be one of the very important pathogens in hospital acquired infections, particularly for compromised host. However the surveillance of the route of coagulase-negative staphylococci infection in hospital is not so easy, as they are the common resident flora of human being. From this point of view, the combination of biochemical testing, bacteriophage typing and the pattern of antibiotic susceptibility is the only useful way to investigate the route of the infection.

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The antibacterial activities of ceftizoxime (CZX) and cefazolin (CEZ) against Klebsiella pneumoniae B-54 in vitro and in experimental pneumonia in mice were examined morphologically by electron microscopy. Furthermore the effects of CZX and CEZ on phagocytosis and bacterial killing of polymorphonuclear leukocytes (PMNs) were examined similarly.
The effects of CZX and CEZ against Klebsiella pneumoniae B-54 were bactericidal and showed greater response to increased doses. At the subminimal or minimal inhibitory concentrations of CZX and CEZ filamentous cells were induced, and with increased concentrations of drugs spheroplasts and bulges were formed which subsequently lysed in vitro.
In the treatment of experimental pneumonia in mice, the administration of CZX at 20mg/kg, ×4 and CEZ at 80mg/kg, ×4 showed lysis obviously in the infected organisms. In particular, 99% of the infected organisms became spheroplasts or lysis by the administration of CZX at 80mg/kg, ×4, which correlated with a significant decrease of viable counts in murine lung. CZX was significantly superior to CEZ on the bactericidal effects against experimental Klebsiella pneumoniae in mice. As a divided administration of CZX and CEZ was more bactericidal than a single administration, it seemed that the continuance of an effective concentration of CZX and CEZ was important to the antibacterial effects.
The ratios of phagocytosis of PMNs in treated PMNs increased about two times and the phagocytized bacterial counts in PMNs increased about three times in comparison to the untreated PMNs. Spheroplasts or lysis were observed in only 9% of phagocytized bacterias in untreated PMNs, but they were observed to be from 73% to 95% of phagocytized bacterias in treated PMNs but no significant differences on the morphological changes were observed between CZX and CEZ. It was concluded that CZX and CEZ were not only bactericidal, but also enhanced the phagocytosis and killing of PMNs against Klebsiella pneumoniae.

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34 male patients with gonococcal urethritis were treated with cefoxitin administered concomitantly with probenecid at the Urological Ward of Tokyo Metropolitan Taito Hospital during the period from July to October in 1982, and clinically evaluated. 50 strains of Neisseria gonorrhoeae isolated from the clinical specimens of these patiena were bacteriologically studied.
Of the 50 strains, 10 (20%) were PPNGs and MICs of PCG and CER to the 10 strains were higher than 100μg/ml. While MICa of CFX to the 50 strains were 0.2×8.25μg/ml. CFX was susceptible to the PPNGs.
Those patients with gonococcal urethritis were given a single 2g intramuscular dose of CFX and a single 1g oral dose of probenecid.
The following clinical findings were obtained:
1) The clinical efficacy rate of 34 cases was 94%: excellent in 14, good in 18 and poor in 2 cases.
2) All 8 patients with gonococcal urethritis caused by PPNGs were cured with the treatment.
3) An allergic reaction (a mild shock) was observed in one patient with CFX, but the patient soon recovered.
No other adverse effect were found.

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BH-AC is a masked compound of Ara-C. The pharmacokinetics of BH-AC and produced Ara-C were studied by HPLC (BH-AC) and bioassay (Ara-C).
1) Blood level; T_1/2β of BH-AC in the blood in mice and rabbits was 0.43 hr. and 0.59hr., respectively after iv injection. The blood level of Ara-C produced from BH-AC was not so high, but persisted for several hours. While, the blood level of Ara-C after Ara-C injection showed high maximum level but very short duration.
2) Tissue level; BR-AC was distributed highly in the liver, spleen, lung, kidney and tumor tissues, and Ara-C from BR-AC was continuously found in the spleen, liver, kidney, testis and tumors in Sarcoma 180 bearing mice. BH-AC was moderately excreted in the bile, but not in the urine.
3) Metabolism; BH-AC was activated to Ara-C in the homogenates of the liver, spleen, kidney and tumor tissues (colon cancer, ALL) from man, and in the liver, spleen, thymus, testis and tumor tissues (S. 180, P-388, L-1210) from mice.
Ara-C was inactivated to Ara-U strongly in the homogenates of the liver, spleen, lung, stomach, intestine, etc. from man, while moderately in the kidney and intestine from mice.
BH-AC persisted in the tissues and released Ara-C for a long time. It must be cared that the strength of the metabolism of BH-AC and Ara-C has a wide variation among animals, organs and various tumors.

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Determination of minimal bactericidal concentrations (MBCs) of antimicrobial agents has become much easier by the use of Dynatech MIC 2000 system. Thus it is now possible to determine MBCs of several drugs against many strains at various points in time during incubation. The results obtained by the present method differ only slightly from those obtained by the conventional method of counting viable cells on agar plates. The MBC determined by Dynatech MIC 2000 system represents the lowest concentration with which 99.5 per cent of bacilli is killed during incubation with a drug.
We have determined MBCs of six cephems (CEZ, CMZ, CTM, CZX, CPZ and LMOX) a against ten patient-strains each of E. coli, K. pneumoniae, S. marcescens and E. cloacae at various points in time of incubation, namely at 3, 6 and 24 hours. The MBC thus determined was compared with minimal inhibitory concentration (MIC).
It was found that the MBCs at 24 hour-incubation (24 h-MBCs) of all the six cephems tested were at nearly the same levels as those of MICs. The MBCs at 6 hour-incubation (6 h-MBCs) of the above cephems against test strains of E. coli and K. pneumoniae were at most eight times higher than the MICs. 6 h-MBCs against S. marcescens and E. cloacae were twice to 64 times higher than MICs. The 3 h-MBCs against four species of gram-negative bacilli of all the cephems examined were much higher than MICs.
Bactericidal effects of CZX, CPZ and LMOX on S. marcescens IFO 3736 were evaluated by the conventional method of counting viable cells on agar plates. After 6 hour-incubation at a 6 h-MBC, the size of the initial inoculum was decreased to 1/100 with CZX, 1/128 with CPZ and to 1/240 with LMOX. This result indicates that the MBC determined by Dynatech MIC 2000 system correlates closely to the results obtained by the conventional viable counting method.
In addition, it was found that, of the cephems examined, ceftizoxime exhibited the most potent bactericidal activity against four species tested, as evidenced by the results of determination of 3 hand 6 h-MBCs.

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Laboratory and clinical studies were performed on HI-89, a new long-acting cephalexin- tablet, and the results were as follows.
1) Serum concentrations of cephalexin were measured in healthy volunteers given orally HI-89 500mg. Mean serum levels of 3 cases were 1.69μg/ml at 1 hr, 4.56μg/ml (peak) at 4 hr, 3.06μg/ml at 8 hr, 1.37μg/ml at 10 hr after the administration. Those of other 2 cases were 3.63μg/ml at 1 hr, 5.21μg/ml (peak) at 4 hr, 0.45μg/ml at 8 hr, and 0μg/ml at 10 hr after the administration. Those of another case were 3.29μg/ml at 1 hr (peak), and 0μg/ml at 8 hr after the administration. Urinary recovery rates of these cases were 80-90%, mean 78%, except one case of 28%, who did not maintain its high serum level.
2) HI-89 was administered to 12 patients with pneumonia (1 patient), bronchitis (5), tonsillitis (3), pharyngitis (2), and fruncle (1). The clinical response was excellent in 4, good in 3, fair in 3, and poor in 2 patients. Bacterial effect was good against S. aureus, S. pyogenes, and relatively good against H. influenzae. As the side effects, diarrhea, abdominal pain, anorexia, nausea, sad constipation were observed in 3 patients. No change was seen in laboratory findings.

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Susceptibility of Enterobacter cloacae to ceftizoxime was distinguishable from that of Escherschia coil or Klebsiella pneumoniae in its heterogeneous distribution. The participation of β-lactamase in this heterogeneous susceptibility of E. cloacae was investigated. One hundred clinical isolates of E. cloacae were classified into fifteen groups according tothe isoelectric points of their chromosomal β-lactamases, which ranged from 8.8 to 10.1. Eighteen strains produced plasmid-mediated penicillinase (PI=5.5) together with chromosomal β-lactamese. Most strains fell under A group (PI=8.8, 39%), followed by G group (PI=9.5, 24%). The distribution profileof ceftizoxime susceptibility of each group was not much different from that of the gross of E. cloacae strains. Meanwhile, β-lactansaae productivity of E. cloacae varied widely with strains and the productivity either in the absence or presence of an inducer correlated well with susceptibility to ceftizoxime among the strains of the same group. These results suggest that the heterogeneous susceptibility of E. cloacae to ceftizoxime arises not from the presence of subspecies in E. cloacae but from a wide variety of β-lactamase productivity of E. cloacae strains. Plasmid-mediated penicillinase scarcely affected the susceptibility of E. cloacae to ceftizoxime whereas it reduced markedly the susceptibility to cefoperazone.

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