Effect of antibiotics on the resistance of white mice to C1. perfringens toxin]

The effect of potassium benzylpenicillin, streptomycin sulfate and chlortetracycline on experimental gangrenous intoxication was studied. When the antibiotics were injected before intoxication, the albino mice resistance did not significantly change. When the antibiotics were injected immediately after the toxin administration, the resistance of the test animals markedly decreased.     

Effect of hydroacridine derivatives on the sensitivity of polyresistant strains of Staphylococcus aureus and Escherichia coli to antibiotics]

Sensitivity of 4 clinical strains of Staph. aureus and E. coli to 13 hydroacridine derivatives and their combinations with antibiotics, such as benzylpenicillin, ampicillin, semi-synthetic penicillins, streptomycin, chloramphenicol, tetracycline, chlortetracycline, monomycin, oleandomycin and erythromycin was studied. The highest bacteriostatic effect was observed on the use of perhydroactidine derivatives with benzylpenicillin or ampicillin with respect to polyresistant penicillinase-producing strains of Staph. aureus, resistance of which to these antibiotics was decreased 250--1000 times. Under the effect of the above compounds the staphylococcal resistance to chloramphenicol, tetracycline, chlortetracycline, oleandomycine and erythromycin decreased 2--66 times. The combinations of hydroacridine with the antibiotics, except 10-amino-trans-syn-trans-perhydroacridine had no effect on the resistance of the E. coli strains. The results of the combined effect of the above substances were associated with their chemical nature, the bacterial type and possibly the character of the strain resistance.     

Activity of Diphtheria Toxin II. Early Events in the Intoxication of HeLa Cells

The initial steps in the interaction of diphtheria toxin with HeLa cells were studied. It was demonstrated that lethal doses of toxin are rapidly adsorbed to the cell. The kinetics of uptake, as measured by lethality, indicated that a single toxin molecule is able to cause cell death. Studies on the effect of pH on intoxication showed that adsorption of toxin occurred over a wide pH range but was partially inhibited at high pH values. Experiments to determine the influence of the ionic environment on intoxication indicated that adsorption of toxin did not take place in the absence of salts and was partially inhibited in the presence of a polyanion. The evidence indicates that the initial binding of toxin to the cell is electrostatic in nature, involving positively charged surface groups. Attempts to demonstrate specific receptors for the attachment of toxin to cells were unsuccessful, suggesting that toxin adsorption may be a nonspecific process. The effect of energy inhibitors on intoxication was examined. Sodium fluoride, an inhibitor of glycolysis, almost completely prevented intoxication in HeLa cells, whereas inhibitors of respiration and oxidative phosphorylation had no effect. Sodium fluoride did not prevent adsorption of toxin but appeared to inhibit a later step in the intoxication process, perhaps the transport of toxin to subsurface or intracellular levels.     

Functional state of the testis after the use of certain antibiotics and nitrofuran preparations]

The functional state of the testis due to the effect of antibacterial therapy was studied in 50 patients suffering from chronic inflammatory diseases of the urinary-genital system and treated with neomycin, streptomycin, tetracycline, furadonin and furagin. It was shown that the above nitrofurans and neomycin had a negative effect on the testis function lowering the number of the spermatozoa in 1 ml and the whole ejaculate and their mobility. Contrary to it tetracycline therapy had no significant effect on the spermatozoa number, while the use of streptomycin was accompanied by a certain tendency to an increase in their number. The data were to some extent in certain accordance with the results of the experimental studies.     

Changes in the phagocytic activity of macrophages under the action of different doses of antibiotics]

Penicillin, streptomycin and gentamicin, when introduced into mice in a single injection in doses of 0.5-500,000 U/kg, produced different changes in the phagocytic activity of mouse peritoneal macrophages. Bactericidal doses of these antibiotics either suppressed the activity of macrophages or left it unchanged. Their sub-bactericidal doses enhanced the phagocytic activity of macrophages. Combined use of penicillin and streptomycin produced a synergic effect.     

Drug resistance stability in staphylococci under different conditions. The mechanism of the recovery of streptomycin sensitivity of a staphylococcal population in patients 7 months after hospital discharge

A method for analysis of antibiotic sensitivity restoration in staphylococcal populations in humans is described. The mechanism of streptomycin sensitivity restoration in staphylococcal populations on the nasal mucosa of 59 patients 7 months after discharging from surgical stationary was studied. Quantitative estimates for loss of superinfecting streptomycin-resistant staphylococci, initial streptomycin-resistant staphylococci and resistance determinants by the initial streptomycin-resistant staphylococci are presented.     

Interaction of staphylococcal enterotoxin B with cell cultures of human embryonic intestine

Schaeffer, W. I. (Massachusetts Institute of Technology, Cambridge), J. Gabliks, and R. Calitis. Interaction of staphylococcal enterotoxin B with cell cultures of human embryonic intestine. J. Bacteriol. 91:21-26. 1966.-The cytotoxic effect of staphylococcal enterotoxin B upon human embryonic intestine cell cultures is characterized by retraction of cells from the monolayer. This is followed by clumping of the retracted cells to form clear areas in the monolayer and finally by sloughing of the clumps from the glass surface. The 50% effective dose of the toxin, determined by protein analysis of the cultures used in titration studies, was found to be between 40 and 60 mug/ml. The cytotoxic property of the enterotoxin was completely neutralized by 3.9 x 10(-5) ml of specific antitoxin per mug of toxin. The cytotoxicity was found to be slightly enhanced by 2.2 g of bicarbonate per liter of Eagle's basal medium (Earle's salt solution level), the absence of serum, the absence of penicillin and streptomycin, and the presence of 2.8 mmoles of calcium in the medium. The cytotoxicity was profoundly influenced by the age of the culture. No cytotoxicity was evident until after 2 days of growth had taken place, when the cell number was approximately 4.0 x 10(5) cells per culture.     

Effect of proteolytic enzymes on antibiotic distribution when the preparations are administered by different routes]

The effect of proteolytic enzymes, such as terrilitine and chymotripsin on pharmacokinetics of morphocycline and streptomycin in rats after their administration by various routes was studied comparatively. The oral use of the enzymes or their introduction directly into the duodenum simultaneously or 30 minutes before the antibiotic administration did not increase the morphocycline and streptomycin levels in the biosubstrates tested. A tendency to a decrease in the serum and organ levels of the antibiotics in animals when used orally in combination with the enzymes was noted. When the drugs were administered intramuscularly, the morphocycline serum and organ levels in the rats increased insignificantly, while the streptomycin levels increased significantly. Administration of formalin as a stressor had an analogous effect which provided a supposition of a possibility of non-specific effect of the enzymes of distribution of the antibiotics on intramuscular injection of the enzymes in large doses having a local irritating effect.     

Heat stability and species range of purified staphylococcal alpha-toxin

Cooper, Louis Z. (New England Medical Center Hospital, Boston, Mass.), Morton A. Madoff, and Louis Weinstein. Heat stability and species range of purified staphylococcal alpha-toxin. J. Bacteriol. 91:1686-1692. 1966.-Heating of high-titer purified staphylococcal alpha-toxin at 60 and 80 C resulted in a double-sloped curve of inactivation of the hemolytic effect on rabbit erythrocytes. Early inactivation was less at the lower temperature, but activity persisted for a longer time at 80 C. Toxin inactivated at 60 C showed renewed activity when heated briefly at 80 C. A precipitate which formed during heating of alpha-toxin at 60 or 80 C yielded hemolytic activity when resuspended and heated at 80 but not at 60 C. Supernatant fluid of heat-precipitated toxin was heat-labile and did not regain activity when heated at 80 C. The results indicate that the "paradoxical effect" of heating of staphylococcal alpha-toxin is not due to a thermolabile inhibitor, but results from alteration of the toxin molecule to a heat-stable active form. Demonstration of renewed activity by 80 C heating of purified toxin requires potent toxin preparations and brief heating periods. Hemolysis of erythrocytes of several animal species by purified alpha-toxin was generally similar to that produced by impure toxin. Rabbit cells were most susceptible. Human and horse erythrocytes hemolyzed to less than 0.1% of the extent of rabbit cells. Blood cells of other species were intermediate in their response to the lytic effect of alpha-toxin.     

Action of Lincomycin on Staphylococci

On a solid medium, 0.1 to 1 μg/ml of lincomycin hydrochloride had a bacteriostatic effect upon 95 of 100 strains of staphylococci. Using cellophane transfers, we observed a bactericidal effect upon 54 of these strains after 3 to 14 hr of contact with 1 μg/ml. Five staphylococcal strains resistant to 100 μg/ml of lincomycin were also resistant to penicillin G, streptomycin, erythromycin, tetracycline, chloramphenicol (three strains), and rovamycin (three strains). Other staphylococcal strains resistant to methicillin, ampicillin, tetracycline, streptomycin, chloramphenicol, and erythromycin were sensitive to lincomycin.     

Dose-dependent effect of penicillin on activity of metabolic enzymes in Staphylococcus epidermidis]

The study was concerned with investigation of the biochemical properties, antibiotic resistance and the effect of various doses of penicillin on the activity of metabolic enzymes in the bacterial cells of Staphylococcus epidermidis isolated from the pharynx mucosa of healthy subjects. The study revealed an increase in the aggressive properties of the representatives of the mouth normal microflora. It was also observed that the highest percentage of the staphylococcal isolates was resistant to beta-lactam antibiotics. The effect of various concentrations of penicillin on the microbial metabolism was shown to be directed at different targets. Penicillin intensified the aerobic processes and lipid synthesis in the bacterial cells. The reactions of the processes of the amino acid metabolism proceeded in different directions. Some concentrations of penicillin inhibited such processes.     

Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication]

The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).     

Interference by Trypsin in the Interaction of Staphylococcal Enterotoxin B and Cell Cultures of Human Embryonic Intestine

The inhibitory effect of trypsin on the cytotoxicity of staphylococcal enterotoxin B acting with human embryonic intestine cell cultures was examined. Trypsin treatment of the cells rendered them resistant to enterotoxin for a period of 48 hr. The resistance increased proportionally with increased time of exposure of the cells to trypsin. Neither ethylenediaminetetraacetic acid nor scraping, which were used as alternate means of cell suspension, caused any resistance to the toxin. The effect is enzymatic and appears to be similar to the inhibitory action of trypsin and chymotrypsin on the attachment of polioviruses and coxsackieviruses to HeLa cells.     

2000年至2006年屎肠球菌的临床分离与耐药变迁

目的了解本地区屎肠球菌在临床的分离与耐药变迁情况,为临床抗感染的预防与治疗提供帮助。方法用WHONET 5软件统计分析我院2000年至2006年屎肠球菌临床分离株在各病区、样本中的分布与耐药性的变迁情况。结果分离率呈逐年上升趋势,从2000年的0.32%上升到2006年的0.81%;7年中以重症监护病区（ICU）分离菌株最高,占总分离菌株的68.9%,其次为肾内科病区占13.5%;在送检标本中以尿液标本分离菌株数最高,占总分离数的62.3%,其次为痰液（10.2%）。对11种抗生素的耐药性分析显示,屎肠球菌对青霉素G、氨苄西林、庆大霉素500、环丙沙星、左旋氧氟沙星呈较高的耐药率,而对四环素、呋喃妥因、链霉素2000相对较低;更值得我们注意的是对于万古霉素的耐药率呈逐年上升趋势,对于喹奴普汀/达福普汀、力奈唑烷这两类临床还未运用的抗生素已有一定的耐药率。结论屎肠球菌在临床的分离率在逐年增加,已成为医院内感染的主要病原菌之一,该菌呈多重耐药的特性,并呈不断增加趋势,临床抗感染治疗应以分离菌株的体外抗菌药物敏感性为依据。     

Antibiotic Therapy of Staphylococcal Infections

The antibiotic treatment of staphylococcal infections remains a problem. Isolation of the organism and sensitivity testing are necessary in the choice of antibiotic. Penicillin G is the most effective penicillin against non-penicillinase-producing staphy-lococci; for the penicillinase producers there is very little to choose between the semisynthetic penicillins, methicillin, cloxacillin, nafcillin and oxacillin. For patients who are hypersensitive to penicillin, the bacteriostatic drugs (erythromycin, novobiocin, tetracycline, chloramphenicol, oleandomycin) are useful for mild infections, while for more severe illness the bactericidal drugs (vancomycin, ristocetin, kanamycin, bacitracin, neomycin) have been used successfully. Acute staphylococcal enterocolitis is probably best treated by a semisynthetic penicillin. Other antibiotics which have been found useful, with clinical trials, for staphylococcal infections are cephalosporin, fucidin, cephaloridine and lincomycin. The latter drug has been reported of value in the treatment of osteomyelitis. There is little justification for the prophylactic use of antibiotics to prevent staphylococcal infection. Surgical drainage is still an important adjunct in the treatment of many staphylococcal infections.     

Recombinant plasmid obtained from two different, compatible staphylococcal plasmids.

From two different, compatible staphylococcal plasmids that determine streptomycin and chloramphenicol resistance, respectively, a recombinant plasmid was obtained. This plasmid can be transduced with a rather high frequency (10(-4)/plaque-forming unit) to plasmid-negative strains, the linkage of the two markers being 100%. The maintenance of the recombinant plasmid in the host cell seems to be controlled by the chloramphenicol resistance plasmid. The recombinant plasmid proved to be incompatible with both parental plasmids, which are unrelated. The relationship between the chloramphenicol resistance plasmid and the recombinant plasmid was the same as the between genetically marked derivatives of the recombinant plasmid, whereas the relationship of the streptomycin resistance plasmid to the recombinant plasmid was of a different, asymmetrical type.     

Complex pathogenetic therapy of experimental botulism

The study of survival and life span of mice and white rats upon the administration of LD50 of the toxin has shown that an antihypoxic agent--gutimine (50-200 mg/kg)--had a protecting effect in type C botulinum intoxication. A combined use of gutimine and 4-aminopyridine (1-5 mg/kg), facilitating a transmitter release in synapses, had a more marked protecting effect in botulinum intoxication. Due to the potentiation of the drugs effect during their combined application, the doses of each drug in the combination could be reduced.     

Dynamics of drug resistance of Vibrio cholerae isolated from surface water reservoirs in Siberia and the Soviet Far East in 1976-1990]

In the study on antibiotic resistance 1383 strains of El Tor Vibrio cholerae isolated from surface water reservoirs in 12 administrative territories of the Siberia and Far East within a period of 15 years were tested. The following antibiotics were used: ampicillin, streptomycin, monomycin, polymyxin, tetracycline, chloramphenicol, rifampicin and nalidixic acid. The resistance was unstable and its pattern was wave-like according to annual changes in the biological cycle. It was especially evident in regard to ampicillin, streptomycin, monomycin and polymyxin. The highest numbers of the strains were resistant to polymyxin, ampicillin and streptomycin (up to 100 per cent in some years). The lowest numbers of the strains were resistant to chloramphenicol (0.4 per cent) and tetracycline (1.9 per cent). No strains resistant to rifampicin and nalidixic acid were isolated. In some cases the antibiotic resistance level depended on the geographical zone where the strain was isolated. A direct quantitative dependence of the resistance level on the MIC was observed: the lower the MIC of the drug was, the lower the number of the strains resistant to it was. Within the 15-year period there was no general tendency to increase the resistance in V. cholerae to the antibiotics used.     

Competitive relations between tetanus anatoxin and toxin]

Experiments were conducted on albino mice; it was shown that preliminary injection of tetanus toxoid enhanced the animal resistance to tetanus toxin, this being expressed in increase in LD50. The effect increased the higher doses of the toxoid and their fractional injection. By using protagon and crude mitochondrial fraction isolated from the brain as a receptor of tetanus toxin in the nervous tissue there were established competitive relations for the receptor between the tetanus toxoid and the toxin. The results of investigations confirmed the authors' earlier statement that the molecule of the tetanus toxin contained different functional groups responsible for the toxin binding with the receptor in the nervous tissue, for the pathogenic action of the toxin and for the binding of the toxin with antitoxin.     

Effect of antibiotics on the resistance of white mice to infection caused by antibiotic-resistant Staphylococcus strains]

The effect of benzylpenicillin, streptomycin and tetracycline on the animal resistance to infection caused by the antibiotic resistant staphylococci was studied. It was found that the effect of the antibiotics on the infectious process outcome was not limited by their antibacterial properties. Changes in the natural resistance of the host under the effect of the antibiotics were not always the same and depended on both the antibiotic type and the moment of its administration.