Efficacy of three-week oxytetracycline or rifampin monotherapy compared with a combination regimen against the filarial nematode Onchocerca ochengi.

Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a major cause of visual impairment and dermatitis in sub-Saharan Africa. As O. volvulus contains an obligatory bacterial symbiont (Wolbachia), it is susceptible to antibiotic chemotherapy, although current regimens are considered too prolonged for community-level control programs. The aim of this study was to compare the efficacies of oxytetracycline and rifampin, administered separately or in combination, against a close relative of O. volvulus (Onchocerca ochengi) in cattle. Six animals per group were treated with continuous or intermittent oxytetracycline regimens, and effects on adult worm viability, dermal microfilarial loads, and Wolbachia density in worm tissues were assessed. Subsequently, the efficacies of 3-week regimens of oxytetracycline and rifampin alone and a combination regimen were compared, and rifampin levels in plasma and skin were quantified. A 6-month regimen of oxytetracycline with monthly dosing was strongly adulticidal, while 3-week and 6-week regimens exhibited weaker adulticidal effects. However, all three regimens achieved >2-log reductions in microfilarial load. In contrast, rifampin monotherapy and oxytetracycline-rifampin duotherapy failed to induce substantive reductions in either adult worm burden or microfilarial load, although a borderline effect on Wolbachia density was observed following duotherapy. Dermal rifampin levels were maintained above the MIC for >24 h after a single intravenous dose. We conclude that oxytetracycline-rifampin duotherapy is less efficacious against O. ochengi than oxytetracycline alone. Further studies will be required to determine whether rifampin reduces oxytetracycline bioavailability in this system, as suggested by human studies using other tetracycline-rifampin combinations.

In vitro studies of the loss of antibacterial activity of oxytetracycline in presence of Ca(II) or Mg(II) ions.

The results of a comparative study, which evaluated the in vitro effect on the antibacterial activity of oxytetracycline (OTC, CAS 79-57-2) in presence of Ca(II)/Mg(II) ions suggest that susceptibility of Staphylococcus aureus, Bacillus pumilis and Bacillus subtilis to OTC is reduced in presence of Ca(II)/Mg(II) ions. As the ratio of concentration of Ca(II)/Mg(II) to OTC was increased, antibacterial activity of OTC declined. In addition to the difference observed between the antibacterial effect of pure OTC and its Ca(II)/Mg(II) complexes, it was found that decline in antibacterial activity is greater for Mg(II)-OTC complex than Ca(II)-OTC complex for the same concentration of Ca(II)/Mg(II) ions.

[Actinomyces rimosus resistance to oxytetracycline]. / Izuchenie rezistentnosti Actinomyces rimosus k oksitetratsiklinu.

High frequency of spontaneous and UV-and acridine dye-induced variants susceptible to oxytetracycline (OTC) and deprived of the capacity for synthesizing this antibiotic was observed in strain LST-118 of Actinomyces rimosus. The cells of strain LST-118 of Act. rimosus contained extrachromosomal DNA not found in its OTC susceptible variant BS87, which provides evidence in favour of participation of the extrachromosomal genetic elements in control of OTC resistance of the cells of Act. rimosus, LST-118. The OTC resistance in strain LST-118 is of inducable character. The resistance level is increasing from the beginning of the antibiotic synthesis and initially the subinhibitory concentrations of OTC in the medium were the inductors triggering cellular mechanisms ensuring resistance of the cell to the increasing concentrations of OTC in the medium. The capacity for absorption of OTC in Act rimosus is 2--3 times lower than that in E. coli. The experiments with labeled tetracycline showed that the cells of the actinomycete absorbed OTC when it was present in the medium. The absorption of the main amount of the antibiotic was registered during the first 5 minutes. The difference in absorption of OTC by the cells of the antibiotic resistant and sensitive strains was insignificant.

[Tetracycline inactivation by magnesium sulfate in testing for microbial contamination by the membrane filtration method]. / Inaktivatsiia tetratsiklinov sernokislym magniem pri ispytanii mikrobnoi obsemenennosti metodom membrannoi fil'tratsii

It was shown that the residual amounts of tetracyclines adsorbed on membrane filters may be inactivated by addition of 2M magnesium sulphate solution to the agar for placing the filters after filtration. The antibiotic inactivation increases the possibilities of the test for antibiotic sensitivity of the microflora present in the drugs and may be used in determination of microbial dissmination of non-injection tetracyclines.

["De novo substituent constants" in the study of quantitative structure-activity relationship]. / "De novo substituent constants" nello studio delle correlazioni quantitative struttura chimica-attività biologica

The basic features of the Free-Wilson method for assigning additivity constants to structural features of related compounds is described. The method is presented in considerable operational detail with special emphasis on its development. An original example is discussed. Showing that the substituent constants can be related to more fundamental physico-chemical substituent parameters such as the hydrophobic constants pi.

[Tetracycline resistance and cell-free systems of protein and polypeptide synthesis]. / Tetratsiklinrezistentnost' i beskletochnye sistemy belkovogo i polipeptidnogo sinteza

Acellular systems of synthesis of polyphenylalanin containing the supernatant fraction from E. coli B and ribosomes from an oxytetracycline sensitive strain of E. coli and strains resistant to that antibiotic were almost equally sensitive to oxytetracycline. The supernatant fraction from the cells of E. coli 241, a resistant strain absorbing significant amounts of oxytetracycline lowered the inhibiting effect of oxytetracycline in the acellular systems of protein synthesis (with an endogenic matrix). No fermentative inactivation of oxytetracycline by that fraction was found with both the biological and radiochromatographic methods.