Complete Cross-resistance Research Articles

Capreomycin in the re-treatment of patients with pulmonary tuberculosis

Summary Capreomycin was administered in combination with other drugs in sixteen patients with far-advanced pulmonary tuberculosis who had failed to undergo sputum conversion on previous combined chemotherapy. Among eleven patients treated with capreomycin for more than 6 months, three became sputum negative on culture and remained so for a follow-up period of several months. In two of these cases capreomycin had been administered with cycloserine and in the third case with 4-4′ diisoamyloxythiocarbanilide, both companion drugs being administered for the first time. A complete reciprocal cross-resistance with viomycin was found in all cases developing resistance to capreomycin during treatment.

The metabolism of some cyclodiene insecticides in relation to dieldrin resistance in the adult housefly, Musca domestica L.

Abstract Studies of the fate of dieldrin in vivo in dieldrin-susceptible (S-flies) and dieldrin-resistant houseflies (R-flies) have led to the conclusion that the resistance mechanism involves factors other than detoxication. Additional evidence in support of this view has been obtained in a study of related, moderately toxic cyclodiene compounds to which dieldrin-resistant houseflies show complete cross-resistance. The pyrethrin synergist sesamex inhibits the metabolism of these compounds to a similar extent in both S- and R-houseflies. This inhibition is accompanied by considerable increases in toxicity to S- but not to R-flies, which suggests that the resistance to these compounds is not dependent upon their metabolism in vivo. By inference, dieldrin resistance is likewise independent of possible dieldrin detoxication, especially since sesamex does not synergize dieldrin against R-flies.

SPIRAMYCIN: A REAPPRAISAL OF ITS ANTIBACTERIAL ACTIVITY

Spiramycin was less active than erythromycin in vitro against sensitive strains of Staphylococcus aureus, but was as effective against staphylococcal infections in mice when the drugs were administered immediately after infection: spiramycin was relatively more effective in prophylactic experiments when the antibiotics were administered at 4 or at 6 hr before infection. Strains of staphylococci which had been habituated to either spiramycin or erythromycin in vitro showed complete cross-resistance to both antibiotics in vitro, but the majority of a number of erythromycin-resistant strains isolated from patients were sensitive to spiramycin in vitro. Spiramycin was effective against a number of such strains in vivo, but erythromycin had little effect against these infections. Investigation into the distribution of the antibiotics in the serum and tissues of mice showed that spiramycin was maintained in tissues (lung, liver, kidney, spleen and heart) at higher concentrations and for a longer period than erythromycin, although erythromycin was initially present in serum in higher concentrations. It is suggested that the efficacy of spiramycin against experimental infections is due to its persistence in the animal body.

Biological spectrum of some new tuberculostatic 1,3,4-oxadiazolones with special reference to cross-resistance and rates of emergence of resistance.

THE tuberculostatic activity of 5-(4-pyridyl)-1,3,4-oxadiazolone (S 57) has been repeatedly confirmed1–3, and complete cross-resistance with isonicotinic acid hydrazid (isoniazid) in laboratory tests using Mycobacterium tuberculosis is reported by all workers in this field. It was, therefore, a little surprising to find that, whereas isoniazid is practically inactive against human leprosy, but active against rat murine leprosy, S 57 is highly active against both animal and human leprosy4–6.

食品防腐剤に関する研究-IV

Acquisition of resistance against chlortetracycline (CTC) by Pseudomonas fluorescens, which is closely associated with putrefaction of fish and shellfish, was studied. The results may be summarized as follows: 1. Three starins of P8. fluorescens were exposed to CTC of either a constant dose at the maximal tolerance level (M. T. L.) of each strain or 0.1 ppm, or an increasing dose at M. T. L. at each stage. After 60 successive subculturings in nutrient broth (Difco) containing a constant dose of CTC, the organisms acquired 4 to 16-fold higher resistance at the M. T. L. and 2 to 8-fold at 0.1 ppm, while the corresponding values obtained at the increasing dose were 16 to 64-fold that of the original culture (Figs. 1 and 2). The resistance acquired in vitro seemed to be comparatively stable since 25 successive subculturings of the in vitro resistant organisms in plain nutrient broth held almost the same level of their resistance. 2. A complete cross-resistance against CTC and oxytetracycline was observed. A slight cross-resistance against chloramphenycol was recorded with the CTC-resistant organisms, while that against streptomycine was not appreciable (Table 1). 3. No marked difference in the biochemical characters, especially those relating to putrefaction, was observed between the resistant and sensitive strains (Fig. 3). 4. The distribution curve of resistance of individual cells of a sensitive strain obtained by plotting the numbers of the colonies counted in agar plates added with various levels of CTC appears to be a S shape (Fig. 4), which indicates heterologous sensitivity to CTC by individual cells. While, the curves for the resistant descendants are composed of two linear lines crossing at nearly right angle, which means the majority of the individuals has the same level of resistance. Neither the sensitive nor resistant strain showed CTC-dependence because the largest number of colonies was counted in the plates without CTC.

Polymyxin B and Colistin: Activity, Resistance and Crossresistance in vitro.

Polymyxin B and colistin. 2 closely related polypeptide antibiotics, had similar antibacterial activity against a large number of pathogenic bacteria. Polymyxin was somewhat more active than colistin against 55% of susceptible strains. on the average 3.4 and 4 times as active against most strains of N. gonorrhoeae and H. influenzae, respectively. Highly resistant variants developed on repeated subculture of a strain of A. aerogenes and one of Ps. aeruginosa on agar containing either of these antibiotics; complete crossresistance to the other antibiotic developed in each instance. Single-step mutants of the same strain of A. aerogenes, highly resistant to each antibiotic, were readily obtained by seeding a large inoculum on the surface of agar containing 100 or 200 μg/ ml of that antibiotic; these mutants were completely cross-resistant to the heterologous antibiotic. Antibiotic-dependent variants were not encountered.

Susceptibility and crossresistance of bacteria to four related antibiotics: kanamycin, paromomycin, neomycin and streptomycin.

Summary and conclusionsThe antibiotics kanamycin, paromomycin and neomycin were shown to have essentially the same activity in vitro against strains of Staphylococcus aureus and of various Enterobacteriaceae. Bacteria made resistant to any one of these 3 antibiotics by subcultures on that antibiotic also exhibit virtually complete cross-resistance to the other two. Organisms isolated from infected sources do not show significant cross-resistance between streptomycin and any of these 3 antibiotics. However, strains made resistant in vitro to either kanamycin, paromomycin or neomycin show moderate increases in resistance to streptomycin, and strains made resistant to the latter exhibit only minor increases in resistance to the other 3 antibiotics. With all 4 antibiotics, corresponding parent and resistant variants of the staphylococci were of the same phage type, and resistant variants of K. pneumoniae and E. coli retained their serological specificity. Fecal organisms isolated from patients during oral tre...

Clinical and laboratory observations of a new antibiotic, tetracycline.

The chemical structures of chlortetracycline (Aureomycin) 1 and oxytetracycline (Terramycin) 2 have now been resolved after many months of chemical and biological studies. The close similarity in the chemical structures of these two antibiotics, which was revealed by these studies, had long been suspected on the basis of the almost identical spectrums of their antimicrobial activity and from the almost complete cross resistance between them. 3 Common to both of these antibiotics is the following structure:The name tetracycline has been proposed for this antibiotic. Chlortetracycline differs from oxytetracycline by the presence of one chlorine atom in the former that is absent from the latter and the presence of a hydroxyl group in oxytetracycline that is absent from chlortetracycline. The structures of these two antibiotics are as follows: The preparation of tetracycline by the catalytic hydrogenation of chlortetracycline, using palladium as a catalyst, was reported recently by workers of both

Cross-resistance among 3 tetracyclines.

ConclusionsOrganisms made resistant in vitro to either tetracycline or oxytetracycline by repeated subcultures in these antibiotics developed essentially complete cross-resistance to each other and to chlortetracycline. No cross-resistance or increases in sensitivity to penicillin, streptomycin, bacitracin, polymyxin, neomycin or erythromycin developed as a result of the increases in resistance to the tetracyclines. Three strains of coliform-resistance to chloramphenicol following subcultures in either tetracycline ro oxytetracycline, but similar cross-resistance was not observed in 5gram-positive coccal strains.