Clinical use of rubomycin in neuroblastoma in children]

The results of treatment of 23 children at the age of 7 months to 11 years suffering from neuroblastoma are presented; 22 patients with tumors, relapses or metastases were subjected to the treatment and 1 child was treated prophylactically after radical operation. Four patients were subjected to roentgen therapy in addition to the treatment with rubomycin. The antibiotic was administered intravenously in doses of 0.7--1.5 mg/kg in 1--3 days or daily. The caurse dose (3--12 mg/kg) was determined by the treatment efficiency and the side reactions. The objective effect was observed in 68 per cent of the patients, including the pronounced objective effect (marks 3 and 2) in 41 per cent of the cases. Leucopenia (less than 4000 cells in 1 mm3 of the blood). thrombocytopenia, vomiting (or nousea) and changes in the ECG were registered in 20 (87 per cent), 4,9 and 2 patients respectively. When the results of the treatment were positive, repeated courses of the therapy within 1.5--2 years were carried out; 18 patients died within 4 months to 2 years after the first course of the treatment with rubomycin because of the disease development. No signs of the disease were observed in 4 children with in 3--6 years of observation.     

Belomycetin in the combined chemotherapy of testicular tumors

The results of the treatment of 21 patients with testicle tumors of various histological structure, stages III and IV, are presented. The combination of bleomycetin (bleomycin A5), an antitumor antibiotic made in the USSR, with vinblastine and platinum derivatives was used. The antitumor effect was observed in 63 per cent of patients, including 21 per cent of patients with complete regression of tumors. The periods of complete and partial remission were 3--13 and 1--9 months, respectively. The combination is sufficiently effective and may be recommended for the treatment of patients with disseminated malignant tumors of the testicle.     

Side effects of antibiotics in rheumatic diseases]

Complications due to antibiotic therapy in rheumatic patients subjected to season bicillin prophylaxis in Minsk within 1965--1975 and in patients with extensive collagenoses were studied. Allergic complications mainly ih the form of allergic reactions in the patients treated with bicillin-3 or picillin-5 were observed in 7.8--16.8 per cent of the patients. Within 10 years 52 cases of anaphylactic shock due to the bicillin use were recorded. Side reactions to antibiotics were observed in 16 (17.3 per cent) out of 92 patients with extensive collagenoses. For prophylaxis of the above complications it is recommended to use rational antibiotic therapy in rheumatic patients, strict registration of allergological states in the anamnesis, testing of microbial sensitivity to the antibiotics.     

Antibiotic sensitivity and the characteristics of transmissive R plasmids in Shigella belonging to various species]

Sensitivity of 241 Shigella strains isolated from patients at various regions of the USSR in 1975--1978 was tested with respect to 14 antibiotics by the method of serial dilutions. 90.5 per cent of the isolates proved to be resistant to the antibacterial drugs and the greater part of 75.9 per cent of them had multiple resistance. The resistance of the Shigella was most pronounced and frequent with respect to tetracycline, streptomycin, levomycetin, as well as ampicillin and carbenicillin. Gentamicin, cephaloridin, polymyxin M, kanamycin, monomycin, neomycin and rifampicin were highly active against the Shigella. More than 50 per cent of the isolates were sensitive to levomycetin, ampicillin and carbenicillin. Differences in the frequency of the resistant strains and the spectrum of the antibiotic resistance of different Shigella subgroups (species) were observed. The study of 173 multiple resistant Shigella strains showed that about 67 per cent of the strains had a capacity for transduction of the resistance markers into the recipient cells of E. coli. The conjugative R-plasmids were most frequent in Sh. boydii and Sh. sonnei (95 and 95 per cent respectively), less frequent in Sh. flexneri and Sh. newcastle (68 and 53 per cent respectively) and least frequent in the mannitol negative Shigella (25 per cent). The capacity for transduction of R-plasmids in the strains carrying the determinants of resistance to 2 or 3 antibiotics was higher than in the strains carrying the determinant of resistance to one antibiotic. The clinical Shigella strains tested mainly had transmissive R-plasmids of fi--character (79 per cent).     

Protective action of rifampicin in experimental rabies infection of albino mice

The paper presents the results of the experimental study of the action of rifampicin on the process of rabies infection in albino mice contaminated with 1-10 LD50 of the fixed rabies virus. Exposure to rifampicin in doses of 250 and 500 micrograms/mouse (35-70 mg/kg) resulted in survival of 66.7 and 83.4 per cent of the animals respectively while in the controls it did not exceed 16.6 and 25.0 per cent. The average life-span of the albino mice treated with the antibiotic increased 1.6-2.4-fold in comparison with the controls. The chemotherapeutic index of rifampicin representing the ratio of the maximum tolerance dose to the minimum dose providing the protective action was equal to 20. The protective action was observed either after administration of the antibiotic according to the treatment-and-prophylaxis scheme or after administration of its 2- or 3-fold dose once a day immediately after the contamination.     

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.     

Rifampicin in the treatment of infections of non-tuberculous etiology

Clinical efficacy of rifampicin, a semisynthetic broad spectrum antibiotic was estimated in 247 patients with purulent inflammations. It was shown advisable to use rifampicin intravenously in treatment of severe bronchopulmonary pathology, disorders of the bile excretion system, osteomyelitis, severe wound infections and in prophylaxis of postoperative purulent complications in cardiovascular surgery and other cases. High rifampicin sensitivity of staphylococci and streptococci belonging to various species was revealed. Rifampicin was found to be less active against gramnegative pathogens. The isolation frequency of rifampicin sensitive strains of E. coli, Proteus spp., Klebsiella spp. and P. aeruginosa amounted to 88.4, 52.1, 58.8 and 49.3 per cent respectively.     

Isolation and low-temperature preservation of liposomes containing rifampicin

The optimal conditions for preparations of rifampicin-containing liposomes were determined with the methods of mechanical shaking, gas dispersion and and reversible phases. It was found that the percentage of rifampicin incorporation into liposomes depended on the molar ratio of the antibiotic to the lipid (the optimal ratio was 1 : 10), the size and structure of liposomes, the amount of cholesterol added and the lipid membrane charge. Incorporation of rifampicin amounted to 16.1 +/- 2.4, 39.2 +/- 3.2 and 60.5 +/- 2.9 per cent with respect to neutral lecithin multilamellar liposes, liposomes prepared with the gas dispersion method and liposomes prepared with the method of reversible phases, respectively. Cholesterol in a molar ratio to lecithin equal to 2 : 5 or higher and dicetyl phosphate imparting the negative charge to the membrane had an inhibitory effect on the drug uptake by liposomes, while stearyl amine having the positive charge had a stimulating effect. The effect of the cryoprotectors glucose, polyvinylpyrrolidone, poly-ethylene glycole-400 and glycerol on low-temperature preservation and storage of rifampicin-containing liposomes was studied. It was shown that 10--15 per cent solutions of sucrose and glucose had the highest cryoprotective effect, when the two-stage method of freezing was used. It provided almost 84 per cent preservation of liposomal rifampicin. Electron microscopy showed that after defrosting liposomes no significant changes in the size and structure of lipid membranes were observed.     

A potentiometric method of quantitative analysis of rifampicin

A potentiometric procedure for assay of rifampicin was developed. The procedure implies titration of rifampicin as a monofunctional acid by sodium hydroxide solution (0.1 mol/l) in 75 per cent aqueous methanol. The constant ionic strength of the solution is provided by addition of KCl until its concentration is 0.1 mol/l, the titrant concentration being 10 times higher than the antibiotic concentration in the solution. This provides a precise determination of the concentration ionization constant of the antibiotic as a monofunctional acid (pKa 7.33 +/- 0.01) and an insignificant dilution of the antibiotic solution during the titration promoting precise and reproducible results. The procedure error is 0.20 per cent. The variation coefficient is 0.27 per cent.     

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).     

Comparative characteristics of the antibioticograms and biological properties of the staphylococci isolated from patients with various eye diseases]

A total of 1488 examinations of the conjunctival content of patients with various ophthalmic diseases were performed within 5 years (1973--1977). 989 (66.4 per cent) cultures were isolated. Staphylococci were isolated in 79.2 per cent of the patients irrespective of the diagnosis. The plasma-coagulating strains were isolated in 43.6 per cent of the patients with acute conjunctivitis. The plasma-negative staphylococci were more frequent in chronic conjunctivitis (83.5 per cent). A total of 188 strains were studied according to 18 tests. Determination of the antibiotic sensitivity showed that the number of the benzylpenicillin and tetracycline resistant strains among the plasma-coagulating staphylococci was higher in the patients with acute ophthalmic diseases. In chronic conjunctivitis no differences in the antibiotic sensitivity of the plasma-coagulating and plasma-negative strains were noted. Similar antibiotic sensitivity of all plasma-negative staphylococci irrespective of the diagnosis was found. High biological activity of the plasma-negative staphylococci was shown: 74.1 per cent of the isolates possessed phosphatase, 59.8 per cent possessed protease and 88.4 per cent a lysozyme-like enzyme. The strains isolated in chronic conjunctivitis produced protease more frequently that those isolated in acute ophthalmic diseases.     

Trial of the clinical use of mithramycin in treating testicular cancer

The data on efficacy of mitramycin, an antitumor antibiotic in treatment of 32 patients with cancer of the testicle are presented. The objectively pronounced effect was observed in 37.5 per cent of the cases, mitramycin being effective in patients with tumors resistant to bleomycin, vinblastin and cis-dichlordiaminoplatinum. Nausea and vomiting were the most frequent side effects of mitramycin use. The hemorrhagic syndrome was recorded in 2 patients. The regimen of the mitramycin intravenous administration in a dose of 25--30 microgram/kg once in 2 days was well tolerated by the patients and may be recommended for the treatment of testicle cancer.     

Sensitivity of the causative agent of tularemia to antibiotics

Sensitivity of the tularemia causative agent of different geographical races to antibiotics such as streptomycin, tetracycline, gentamicin, rifampicin (20 strains), ampicillin, polymyxin M, erythromycin, oleandomycin (361 strains) and lincomycin (294 strains) was studied. High sensitivity of the tularemi a microbe to streptomycin, tetracycline, rifampicin (MIC of 10 gamma/ml), gentamicin (MIC of 1 gamma/ml) and resistance to 50 gamma of ampicillin and 1000 gamma/ml of polymyxin M were found. Combined use of 50 gamma of ampicillin and 100 gamma/ml of polymyxin M added to the nutrient medium for growth inhibition of the foreign flora on isolation of the tularemia causative agent from the infected material including stable laboratory animal carcases was recommended. Marked differences in sensitivity of the strains of different geographical races to the macrolides and lincomycin were observed. The strains of the non-Arctic and Central Asiatic races were of low resistance to the above drugs (the MIC of erythromycin, oleandomycin and lincomycin were 10--50, 50--400 and 25--100 gamma/ml respectively. Within the holarctic race 40 per cent were low resistant and 60 per cent were highly resistant to these drugs. The above drugs should not be used for treatment of tularemia cases.     

Carminomycin study in breast cancer]

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.     

Treatment of staphylococcal pneumonias

Sensitivity of 129 strains of pathogenic staphylococci isolated from patients with pneumonia was studied with respect to a large number of drugs in the Bacteriological Laboratory of Konstantiny in the Algerian People's Democratic Republic. The method of paper discs and the Müller-Hinton solid nutrient medium were used. The staphylococcal strains were highly sensitive to cephalosporins, some of aminoglycosides (neomycin, gentamicin, tobramycin), nitrofurans, rifampicin, some antibiotics of other groups. Minocycline proved to be the most active among the tetracycline antibiotics. The number of the strains sensitive to it amounted to 82 per cent. 74--76 per cent of the isolates were resistant to tetracycline and oxytetracycline. 40--77 per cent of the isolates were resistant to sulfanilamides.     

Biotransformation of rifampicin in pulmonary tuberculosis patients

Biotransformation of rifampicin in 39 tuberculosis patients treated with the drug was studied. The studies showed that biotransformation of rifampicin was most intensive during the first 3--6 hours after its use, which was confirmed by excretion of maximum amounts of rifampicin and its metabolites with the urine. 2--4 weeks after the beginning of the treatment with rifampicin excretion of its metabolism products decreased. When rifampicin was used simultaneously in a single dose with tubazid excretion of rifampicin transformation product and desacetylation of the antibiotic slowed down.     

Level and nature of the drug resistance of Shigella flexneri]

Characteristics of antibiotic resistance of 300 strains of Shigella flexner 2a isolated from patients within 1976--1977 in the regions where these bacteria were very rare for a long period of time were studied. It was shown that most of the isolates were resistant to chloramphenicol (88.1 per cent), tetracycline (94.8 per cent), streptomycin (89.1 per cent), polymyxin M (82.4 per cent) and others. 46.5--61.6 per cent of the isolates were resistant to neomycin antibiotics. A high level of the resistance was also noted: the bactericidal effect was registered in 52.0-74.0 per cent of the cultures at a dose of 500--1000 microgram/ml. 91.4 per cent of the strains possessed multiple dug resistance, 78.8 per cent of them being simultaneously resistant to 4--7 drugs. Transmissive R-plasmids were found in 68.8 per cent of the isolates. After exposure to acridine dyes the plasmid nature of the resistance was confirmed in 72.3 per cent of the cultures. Variability of the r-determinant sets in r-plasmids was noted. Strains (64.9 per cent) carrying r-determinants Tc, Cm, Sm and Tc, Cm were more frequent. Strains with one transmissive r-determinant were usually solitary.     

Effectiveness of the intramuscular administration of high doses of penicillin in treating pneumonia]

Clinical tolerance of benzylpenicillin administered intramuscularly in doses of 2000000--3000000 units every 4--6hours (12000000 units a day) was studied in 253 patients with pneumonia. Satisfactory tolerance of sodium benzylpenicillin and pronounced painfulness at the site of injection of potassium benzylpenicillin were noted. General toxic side effects in the form of asthenia, dizziness, pain in the heart region were observed in a part of elderly patients. The benzylpenicillin serum levels after administration of 2000000 units were 6--10 times higher than those after administration of 200000 units. The efficiency of benzylpenicillin elevated doses was studied in 193 patients. In 101 of them the previous treatment with usual doses of benzylpenicillin, i. e. 200000 units every 4 hours was not sufficiently effective. The elevated doses of benzylpenicillin proved to be effective in 78 per cent of the cases, the effect being observed in all the cases with acute pneumonia, in 88.5 per cent of the cases with neglected state and in 83 per cent of the cases with chronic pneumonia. The therapeutic effect was also observed in most of the patients with benzylpenicillin resistant microflora in the sputum. On the basis of high efficiency of penicillin therapy it was concluded that gram-positive cocci played the main role in pneumonia etiology.     

Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study

Background

The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia.

Methodology/Principal Findings

Analysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was 62 years (range 3–94 years). 47 (34%) had surgical treatment alone, and 90 (66%) had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic regimens. 13/47 (30%) treated with surgery alone failed treatment compared to 0/90 (0%) of those treated with combination medical and surgical treatment (p<0.0001). There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100%) compared with those not containing a fluoroquinolone (29/29 cases; 100%). Complication rates were similar between ciprofloxacin and rifampicin (31%) and rifampicin and clarithromycin (33%) regimens (OR 0.89, 95% CI 0.27–2.99). Paradoxical reactions during treatment were observed in 8 (9%) of antibiotic treated cases.

Conclusions

Antibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.     

Pharmacokinetics of rifamycin

Rifamycin pharmacokinetics was studied on experimental animals after the antibiotic administration by various routes. Parenteral use of the antibiotic resulted in its high levels in rats and rabbits. Irrespective of the administration route, i. e. intravenous, intramuscular or oral rifamycin satisfactorily penetrated into the rat tissues. The highest antibiotic levels were found in the animal liver. In small amounts the antibiotic was excreted with the urine (about 6 per cent for 4 hours). The extrarenal clearance of rifamycin was lower than the plasmic clearance only by 3 per cent and higher than the kidney clearance almost by 40 times. Rifamycin was bound in close amounts by the blood serum of humans, oxen and rabbits, i. e. by 68, 64 and 56 per cent respectively. The rat organ homogenates bound the antibiotic by 34--72 per cent.