摘要:

Mode of action of 5-fluorocytosine (5-FC) and mechanisms of resistance to the drug are discussed on the basis of experiments performed with Candida albicans ATCC 26790 and with 50 selected clinical isolates of C. albicans belonging to serological type A or B and representing various degrees and models of 5-FC resistance (sensitivity). Incorporation of 5-fluorouridylic acid into RNA appeared as a prerequisite to antifungal activity, although at a given incorporation rate, growth inhibition varied considerably from one strain to the other. The amino acid pool was unbalanced, and there was evidence for disturbance of protein synthesis. These dysfunctions of RNA probably account for growth inhibition and cell death, whereas up to the present, there was no proof of formation of 5-fluorodeoxyuridylic acid nor of subsequent inhibition of thymidylate synthetase. Incorporation of fluorinated pyrimidine into RNA was lower in normally sensitive type B strains than in normally sensitive ones of type A, whereas the frequency of 5-FC-resistant mutants was the same. The two serological types did not differ in the activity of cytosine permease nor in that of cytosine deaminase. Among 29 clinical isolates with 5-FC resistance (or impaired sensitivity) no instance of cytosine permease deficiency was found. Two isolates (belonging to the serological type A) were deficient in cytosine deaminase, whereas the majority was probably deficient in uridine monophosphate pyrophosphorylase or had a surplus of de novo synthesis of pyrimidines. Relative 5-FC resistance was more common than complete resistance.

ISSN:0009-3157    

DOI:10.1159/000221854

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

The inhibitory activity of pyrimethamine (PMA) is 1/290 of the activity of trimethoprim (TMP) against E. coli as evaluated from a plot of C·ko/ko-kapp vs. C. Even at high concentrations the effect of PMA in contrast to TMP seems to be bacteriostatic. Combinations of TMP and PMA reveal an additive effect. In PMA-treated cultures, the slope of the logarithmic growth curve decreases after an initial inhibited growth, and a second steady state is established. This second steady state has a different reason than the one observed in TMP-treated cultures; whereas the second phase in TMP-inhibited cultures depends on the number of germs, in the case of PMA it depends on the number of generations. Using prewashed cell cultures, it was shown that there is no influence on the two steady states in PMA-inhibited cultures; for TMP, however, it was shown that the presence of the first phase is due to an antagonist excreted into the culture medium. These observations hint at differences in the mode of action of TMP and PMA in addition to differences in the affinity to the target enzyme dihydrofolate reductase. Combination of PMA with sulfamethoxazole (SMZ) at concentrations where both drugs are acting only bacteriostatically leads to effects considerably greater than would be expected from simple additivity. The kill rate observed is the same as observed for TMP/SMZ combinations despite of the considerable lower activity of PMA compared to TMP. It is justified to speak of a synergism in action of PMA and SMZ. The results support the assumption that it might be possible to select drug combinations considering the best pharmacokinetical fit and not necessarily the most effective drugs in the series studied

ISSN:0009-3157    

DOI:10.1159/000221855

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

Mecillinam (FL 1060) is a new β-lactam antibiotic particularly active against gram-negative organisms. When given intravenously, very high serum levels were maintained for a short period of time. Lower peak levels but comparable bioavailability were obtained after intramuscular administration. Gastrointestinal absorption of mecillinam is poor, and for effective oral therapy the drug must be given in the form of its pivaloyl-oxymethyl ester pivmecillinam (FL 1039) which is well absorbed and rapidly transformed to mecillinam by enzymatic hydrolysis in the body. Urinary recovery of mecillinam after orally administered pivmecillinam was 45% in the first 6 h compared with 55 and 59% after mecillinam given by the intravenous and intramuscular routes, respectively. By increasing the dose the orally active ester produced proportionally higher levels of mecillinam, and the area under the serum curve was doubled with the dose. Higher peak levels and prolonged maintenance of high serum concentrations were seen after administration of pivmecillinam with probenecid. The presence of food in the stomach did not influence the absorption of pivmecillinam to any great extent

ISSN:0009-3157    

DOI:10.1159/000221856

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

The purpose of the study was the objective evaluation of the mucolytic and antibiotic properties of Fluimucil® Antibiotic, a molecular combination of acetylcysteine and thiamphenicol. The preparation was administered to 45 patients in the dose of 3 tablets daily each containing 500 mg of thiamphenicol. Statistical analysis of the data obtained showed mucolytic effects on the 4th to 5th day of treatment and a marked antibiotic activity. The evaluation is positive particularly if the relatively low dose of antibiotic normally used in chronic bronchitis is considered. The preparation Fluimucil Antibiotic can be recommended for the treatment of chronic bronchitis also in view of its good tolerability

ISSN:0009-3157    

DOI:10.1159/000221857

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

The effect of a 4-day course of co-trimoxazole (Septrin) on antitoxin response to tetanus vaccine was assessed in a double-blind study involving 22 healthy adults. The tetanus antitoxin levels were measured by in vivo and in vitro methods for up to 8 weeks after the first of two injections of tetanus vaccine, given 4 weeks apart. No significant difference was observed in the level of tetanus antitoxin produced in subjects who received co-trimoxazole (Septrin) in recommended therapeutic dosage during the first 4 days of the trial from that in subjects who received placebo tablets. The results indicate that a 4-day course of co-trimoxazole (Septrin) does not affect antibody production.

ISSN:0009-3157    

DOI:10.1159/000221858

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

The penetration of parenterally administered gentamicin into the CSF was examined in dogs. The experiments were carried out in three stages: (1) in healthy dogs, (2) in dogs with meningitis, and (3) during recovery from the acute inflammation. Gentamicin was found to penetrate poorly into the CSF, reaching mean peak levels of 0.7 μg/ml in healthy dogs. During the height of the meningeal inflammation the mean peak gentamicin level in the CSF was 0.9 μg/ml. The ratio of mean maximum CSF to mean maximum serum levels of gentamicin was 5.8% in healthy dogs, and 11.3% in dogs with meningitis. Thus, inflammation increases the penetration of parenterally administered gentamicin into the CSF, but therapeutically adequate levels for gram-negative bacillary meningitis are not achieve

ISSN:0009-3157    

DOI:10.1159/000221859

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

Two of twelve examined S. marcescens strains were promptly killed by 80% (v/v) fresh human serum (within 20 min), analogous to a serum-sensitive control strain of Escherichia coli; ten strains, however, were killed by fresh serum only after extended incubation (2–4 h). The combination of therapeutically achievable concentrations of polymyxin B (range 5 to 1.25 μg/ml) and fresh, but not heat-inactivated human serum was found to exert an accelerated, additive effect against 9 of 10 ‘delayed serum-sensitive’ isolates of S. marcescens, an organism that is characterized by intrinsic resistance against polymyxins. The combination of 80% (v/v) fresh, defibrinated human blood and polymyxin B likewise resulted in an additive effect. Polymyxin B treatment of S. marcescens strains caused a prompt, marked, though reversible bile salt susceptibility of the cells; in contrast, the effect induced by fresh serum was slight and not apparent until several hours after ex

ISSN:0009-3157    

DOI:10.1159/000221860

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

1-β-d-Ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) had significant in vitro activity against type 1 parainfluenza (Sendai) and type 3 parainfluenza (HA-1) viruses. Activity was manifested as inhibition of both viral cytopathogenic effect and of recoverable virus or viral hemagglutinin titer. The minimum Sendai virus inhibitory concentration was determined to be approximately 3.2 µg/ml. Previous studies had determined the minimum concentration inhibiting HA-1 virus was approximately 1–10 µg/ml. The effect of time of addition of ribavirin to virus-infected cells was determined; maximal activity was seen when the drug was added just prior to either virus or within 4–8 h after each virus, although anti-Sendai viral effects were still apparent when ribavirin was added as late as 24 h after the virus. Ribavirin had no effect on adsorption of HA-1 or Sendai virus to cells. Lethal Sendai virus infections of mice were significantly inhibited by multiple intraperitoneal ribavirin treatment, starting either 4 h before or up to 24 h after virus inoculation. Therapy starting 48, 72 or 96 h after virus exposure had a moderate degree of efficacy. Treatment using an aerosol chamber also was of moderate effectiveness, although the procedure was considered traumatic to the animals. A nonlethal, principally upper respiratory tract infection of hamsters induced by the HA-1 virus was inhibited by ribavirin therapy. Treatment administered intraperitoneally, per os or by aerosol chamber resulted in reduced 23-day antibody titers to the virus, presumably because of reduction of virus in the animal. In a separate experiment, intraperitoneal ribavirin therapy resulted in a 1 log10 or less reduction in virus titer in nasal washings from HA-1 virus-infected hamsters, whereas, when the drug was administered intranasally in a dry powder aerosol spray, nasal virus titers were reduced up to 2 log10 and a moderate virus-induced lung consolidation was completely inh

ISSN:0009-3157    

DOI:10.1159/000221861

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

The 2,3-dihydroxy-6-bromo-pyrazino-[2,3-β]-pyrazine is a substance selected during the antiviral screening of pyrazino-pyrazine derivatives. The compound shows antiviral activity in vitro against measles, NDV, some influenza viruses and against herpes simplex and zoster, infectious canine hepatitis and vaccinia viruses. It had no effect on ECHO 9 virus. Therapeutic trials showed activity also on herpetic keratoconjunctivitis experimentally induced in rabbits

ISSN:0009-3157    

DOI:10.1159/000221862

出版商:S. Karger AG    

年代:1975

数据来源: Karger

摘要:

Upon exposure of Enterobacter cloacae to silver sulfadiazine, a number of ultrastructural changes involving the cell envelope take place. Foremost among these is a modification of the cell wall from an undulating structure to one which is smooth and has become enlarged. Strains of E. cloacae resistant to silver sulfadiazine do not exhibit these changes.

ISSN:0009-3157    

DOI:10.1159/000221863

出版商:S. Karger AG    

年代:1975

数据来源: Karger