Relationship between nephrotixic effect of gentamicin and streptomycin and their blood levels in laboratory animals]

A principle of studying the nephrotoxic properties of drugs under conditions of maintaining their constant levels in the blood and dynamic registration of the nitrogen levels in the urea followed by histological examination of the kidney is proposed. Correlation between the levels of gentamicin and streptomycin in the cat blood during 4-hour infusion and the level of the nephrotoxic effect was found, gentamicin being much more toxic than streptomycin.     

Use of sodium nucleinate and its combinations with bacterial polysaccharides for preventing the nephrotoxic action of aminoglycoside antibiotics

Possible prevention of the nephrotoxic effect of different doses of aminoglycoside antibiotics, such as monomycin, kanamycin and gentamicin was studied experimentally on chinchilla rabbits. Substances increasing the cell resistance (sodium nucleinate, prodigiosan and pyrogenal alone and sodium nucleinate combinations with the bacterial polysaccharides) were used. It was shown that sodium nucleinate prevented nephrotoxicity of the aminoglycosides in the doses 2.5 times higher than the therapeutic ones. The combined use of sodium nucleinate with pyrogenal or prodigiosan was most effective. It prevented the nephrotoxic effect of the antibiotics in the doses 5 times higher than the therapeutic ones.     

A Comparison between the Nephrotoxic Profile of Gentamicin and Gentamicin Nanoparticles in Mice

Aminoglycoside antibiotics are widely used against Gram‐negative infections. On the other hand, nephrotoxicity is a deleterious side effect associated with aminoglycoside therapy. Gentamicin is the most nephrotoxic aminoglycoside. Because of serious health complications ensue the nephrotoxicity induced by aminoglycosides, finding new therapeutic strategies against this problem has a great clinical value. This study has attempted to compare the nephrotoxic properties of gentamicin and a new nanosized formulation of this drug in a mice model. Animals were treated with gentamicin (100 mg/kg, i.p. for eight consecutive days) and nanogentamicin (100 mg/kg, i.p. for eight consecutive days). Blood urea nitrogen (BUN), plasma creatinine levels, and histopathological changes of kidney proximal tubule were monitored. It was found that gentamicin caused severe degeneration of kidney proximal tubule cells and an increase in serum creatinine and BUN. No severe injury was observed after nanogentamicin administration. This study proved that nanosized gentamicin is less nephrotoxic.     

Bath treatment of channel catfish with three broad-spectrum antibiotics

Serum drug levels were measured in channel catfish following bath exposure to kanamycin, gentamicin and chloramphenicol. Kanamycin was absorbed at a rate sufficient to attain therapeutic blood levels in several treatment schedules. Therapeutic blood concentrations could not be attained with gentamicin or chloramphenicol following 24 hrs exposure at 80 and 100 microg/ml water concentrations, respectively.     

Features of incorporation of several antibiotics into erythrocyte ghosts--a system of targeted delivery of chemotherapeutic drugs

Features of incorporation of cefazolin, ampicillin, kanamycin and gentamicin into erythrocytic shadows in patients with abdominal diseases and apparently healthy persons during hypoosmotic hemolysis were studied. The highest percentage of kanamycin and gentamicin incorporation into the erythrocytic shadows was observed. The parameter of the antibiotic incorporation from the incubation fluid into the erythrocytic shadows depended on the antibiotic type and dose. Rather significant resistance of the erythrocytic carriers with incorporated gentamicin to possible desorption and excretion of the antibiotic from the shadows into the blood flow was revealed which made their use possible for target release of antibiotics in the liver.     

Kiwifruit ameliorates gentamicin induced histological and histochemical alterations in the kidney of albino mice

Gentamicin is an antibiotic used worldwide for treating Gram-negative bacterial infections. Gentamicin causes nephrotoxicity in up to 25% of therapeutic cases owing to increased production of free radicals. Kiwifruit are nutrient-dense fruits that have proven effective for ameliorating many pathological conditions caused by oxidative stress. We investigated the possible prophylactic and therapeutic effects of kiwifruit on the changes in renal histology and histochemistry caused by gentamicin. Intramuscular injection of mice with gentamicin for 10 consecutive days was nephrotoxic as indicated by epithelial vacuolization, glomerular atrophy and tubular necrosis. Necrotic tubule cells lost most of their polysaccharides and structural proteins. Co-administration of kiwifruit with gentamicin prevented nephrotoxic changes to a modest degree. When administered subsequent to gentamicin intoxication, kiwifruit ameliorated significantly the histological and histochemical alterations caused by gentamicin. Our findings support the use of kiwifruit in cases of acute renal injury due to gentamicin.     

Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea

Summary When DNA fragments from Micromonospora purpurea (the producer of gentamicin) were cloned in Streptomyces lividans, a gentamicin-resistant strain was obtained in which the ribosomes were highly resistant both to gentamicin and to kanamycin. Reconstitution analysis revealed that such resistance resulted from some property of their 16S RNA. Extracts from the clone contained methylase activity which acted on 16S RNA within E. coli 30S ribosomal subunits and rendered them resistant to gentamicin and kanamycin.     

ELISA法检测乙型脑炎减毒活疫苗中卡那霉素和庆大霉素的残留量

用ELISA试剂盒检测乙脑减毒活疫苗中卡那霉素和庆大霉素的残留量。以间接竞争ELISA法检测线性范围内加入高、中、低3种浓度的卡那霉素和庆大霉素,测定其在疫苗稳定剂、疫苗稳定剂10倍稀释溶液、试剂盒稀释液中的回收率,以及在10倍稀释乙脑减毒活疫苗中的回收率。高、中、低浓度的卡那霉素在疫苗稳定剂、疫苗稳定剂10倍稀释溶液、试剂盒稀释液中的回收率为101.40%～124.80%之间;原倍疫苗稳定剂对庆大霉素的测定有明显干扰,在原倍疫苗稳定剂中低浓度和中浓度的庆大霉素的回收率高达2280%和575%,但其它测定条件下回收率在90%～125%之间。在10倍稀释的乙脑疫苗中加入一定量的卡那霉素和庆大霉素,回收率分别为124%和103.25%。用10倍稀释法测定1人份规格的乙脑减毒活疫苗17批、5人份规格的乙脑减毒活疫苗19批。乙脑减毒活疫苗10倍稀释后,可用ELISA试剂盒检测卡那霉素和庆大霉素残留量。     

Optimal Combination and Concentration of Antibiotics in Media for Isolation of Pathogenic Fungi and Nocardia asteroides

Strains of Blastomyces dermatitidis, Sporothrix schenckii, Histoplasma capsulatum, Cryptococcus neoformans, Nocardia asteroides, and Coccidioides immitis were tested for in vitro susceptibility to polymyxin, gentamicin, kanamycin, chloramphenicol, and neomycin at concentrations of 1, 2, 4, 8, and 16 mug/ml. Polymyxin was the most inhibitory and gentamicin was the least inhibitory of the five antibiotics. Two Histoplasma mycelial strains were partially inhibited by 2 and 8 mug of gentamicin per ml and showed at least a 2+ growth at the higher antibiotic concentration. Kanamycin and neomycin produced significant inhibition of N. asteroides but otherwise were noninhibitory. A combination of chloramphenicol and kanamycin, each at 16 mug/ml, and gentamicin, at 4 mug/ml, was noninhibitory to the strains tested except for N. asteroides. Chloramphenicol at 16 mug/ml was not inhibitory for N. asteroides. The results suggest that the optimal antibiotic combination to use in the isolation of fungi and higher bacteria is chloramphenicol, 16 mug/ml, and gentamicin, 4 mug/ml. Addition of sheep blood (5%) had no effect on antibiotic susceptibility of the organisms studied.     

Renal handling and acute urinary electrolyte effects of aminoglycoside antibiotics: Use of a solitary renal autotransplant in the conscious sheep

Renal handling of the aminoglycoside antibiotics gentamicin and tobramycin were studied before and after one hour of constant intravenous infusions adjusted to maintain a concentration of 15 μg/mL. A solitary renal autotransplant model in four conscious volume replete 40 Kg sheep was used. This unique surgical preparation allows sampling of renal arterial and renal venous blood as well as urine drained through an exteriorized parotid-ureteral fistula. This surgical preparation has considerable potential in renal pharmacology since it uses a conscious, large animal. Baseline studies in this preparation demonstrated normal, ⁵¹CrEDTA and ¹²⁵I PAH, clearances which were unaffected by the drugs. Aminoglycoside binding to pooled sheep sera was 11% at physiologic PH. calcium and magnesium concentrations. A–V difference was 1.3 ± .3 μg/mL and extraction by the kidney was 9 ± 3.2% with no differences between gentamicin and tobramycin. Clearance of gentamicin was 84% and tobramycin 86% of GFR. There was no evidence of tubular injury as evidenced by unchanged urinary beta-2 microglobulin excretion. Serum Na, K, Ca and Mg did not change over the course of the study. Both drugs caused a prompt decrease in absolute and fractional sodium excretion while only gentamicin produced a kaliuresis. Early aminoglycoside effects on electrolyte balance may be an eventual determinant of nephrotoxic potential rather than differences in renal drug handling.Nephrotoxicity is a major side effect of aminoglycoside antibiotic therapy. Although gentamicin and tobramycin have similar pharmacokinetics, including renal cortical accumulation, both double blind clinical studies (1) and experimental data (2) have shown that gentamicin is more frequently associated with renal dysfunction. Recent studies in the dog have suggested that hypokalemia due to renal potassium wasting is a risk factor predisposing to nephrotoxicity (3). In clinical usage aminoglycosides may induce hypokalemia and hypocalcemia, perhaps resulting from drug-induced magnesium depletion (4). Previous studies reporting data concerning the acute effects of aminoglycosides on renal function and electrolyte excretion have used anesthetized animals (5) or isolated perfused kidney preparations (6). The present experiments utilize a unique surgical preparation in which a solitary kidney is autotransplanted to the neck of a sheep followed by a contral ateral nephrectomy. Urine flow is exteriorized through a uretero-parotid-cutaneous fistula thus providing a conscious animal with ready access to renal arterial and renal venous blood. Our results show that renal handling of gentamicin and tobramycin do not differ during short-term constant infusions. Both drugs caused a decrease in sodium excretion while gentamicin caused a larger increase in fractional and absolute potassium excretion. This raises the possibility that nephrotoxic properties of aminoglycosides may be secondary to their effects on electrolytes.     

Comparative study of the antibacterial activity of aminoglycoside antibiotics and their combinations with carbenicillin against Pseudomonas aeruginosa

Antibacterial activity of 7 aminoglycoside antibiotics and combinations of tobramycin or gentamicin with carbenicillin was studied with respect to 33 clinical strains of Ps. aeruginosa. Tobramycin, sisomicin, gentamicin and amicacin showed high levels of antibacterial activity. Tobramycin and sisomicin were 3-4 and 2 times more effective than gentamicin. 100 per cent of the Ps. aeruginosa isolates was sensitive to tobramycin and amicacin. The number of the isolates sensitive to sisomicin and gentamicin amounted to 97 and 94 per cent respectively. The respective numbers for streptomycin and kanamycin were 32 and 11 per cent. No monomycin sensitive isolates were detected. Combination of tobramycin or gentamicin with carbenicillin increased the antibacterial activity of the aminoglycoside antibiotics by 2-16 times and that of carbenicillin by 2-32 times. The synergistic effect of gentamicin or tobramycin with carbenicilin was observed with respect to 50 and 58 per cent of the isolates respectively. No antagonistic effect was detected on the combined use of the antibiotics. The majority of the isolates (96 per cent) were sensitive to combinations of carbenicillin in a concentration of 50 micrograms/ml with tobramycin or gentamicin in concentrations of 0.15 or 0.3 micrograms/ml respectively.     

Resistance to gentamicin and related aminoglycosides in Staphylococcus aureus isolated in Brazil

Isolates of Staphylococcus aureus obtained from a Brazilian university hospital were characterized in relation to resistance to gentamicin and related aminoglycosides. Thirty-six isolates were susceptible to methicillin (MSSA) and 14 were resistant (MRSA). All isolates were sensitive to nucleic acid-binding compounds. All MRSA isolates and one MSSA isolate were demonstrated to be resistant to gentamicin and were coincidentally resistant to amikacin, kanamycin, neomycin and tobramycin. Among the gentamicin sensitive MSSA isolates, five isolates were found to be resistant only to kanamycin/neomycin. The resistance to gentamicin (and related aminoglycosides: kanamycin and tobramycin) must be due to AAC(6')-APH(2") activity. As these isolates also showed resistance to neomycin, they must carry an additional genetic element, probably the one responsible for APH(3')III activity, which accounts for the high level of resistance to kanamycin and to amikacin. The resistance to kanamycin/neomycin in the gentamicin sensitive isolates could not be attributed to the AAD(4')(4") activity because of the tobramycin sensitivity, and so could be ascribed to the APH(3')III activity. Curing and transfer experiments, as well as electrophoresis procedures, indicate that gentamicin resistance in Staph. aureus strains here studied has, characteristically, chromosomal localization.     

Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides

Methylation of either of two residues (G-1405 or A-1408) within bacterial 16 S ribosomal RNA results in high level resistance to specific combinations of aminoglycoside antibiotics. The product of a gene that originated in Micromonospora purpurea (an actinomycete that produces gentamicin) gives resistance to kanamycin plus gentamicin by converting residue G-1405 to 7-methylguanosine. Resistance to kanamycin plus apramycin results from conversion of residue A-1408 to 1-methyladenosine catalysed by the product of a gene from Streptomyces tenjimariensis.     

Gentamicin level in the prostate and its pharmacokinetics in patients with benign prostatic hypertrophy]

The study involved 15 male patients with periurethral prostatic adenoma without complete anuresis. The patients were given 80 mg of gentamicin intramuscularly one day before surgery and 80 mg in a one-hour infusion immediately before an operation. Gentamicin blood concentrations were measured. Pharmacokinetic parameters were calculated and dosage schemes for each patient basing on the antibiotic blood levels. Gentamicin levels in removed adenomas were also determined. Adenomas weighed between 18.0 and 45.8 grams while gentamicin concentration ranged from 1.31 to 3.8 micrograms/mL. It was found that gentamicin concentration in adenomas depend upon their weight. Moreover, pharmacokinetic parameters of this antibiotic exert negligible effect on its levels in adenoma.     

Cloning of aminoglycoside-resistance determinants from Streptomyces tenebrarius and comparison with related genes from other actinomycetes

At least two aminoglycoside-resistance determinants from Streptomyces tenebrarius have been cloned separately in Streptomyces lividans. In each case, resistance (to kanamycin plus apramycin or to kanamycin plus gentamicin) was expressed at the level of the ribosome and involved specific methylation of 16S ribosomal RNA. Hybridization and restriction analysis revealed that related genes were present in other aminoglycoside-producing actinomycetes.     

The effect of gentamicin on calcium uptake by renal mitochondria

The effect of the nephrotoxic aminoglycoside antibiotic, gentamicin, on calcium uptake by renal cortical mitochondria was assessed in vitro. Gentamicin was found to be a competitive inhibitor of mitochondrial Ca⁺⁺ uptake. This effect displayed a dose response with a K_i of 233 μM and occurred at gentamicin concentrations below those that inhibit mitochondrial electron transport. These results further demonstrate the potential for gentamicin to alter membrane function and thereby contribute to toxic cell injury via its interactions with divalent cations.     

Toxicity of gentamicin in organ culture of fetal rat intestine.

The effect of gentamicin in the culture of fetal rat intestine was studied. Fetal rat intestine was cultured with gentamicin or kanamycin at the concentration between 4 to 200 micrograms/ml. Kanamycin did not have influence on lactase, maltase and ALP activities. On the other hand, gentamicin caused decrease of lactase and ALP activities at the concentration of 40 and 200 micrograms/ml compared with the activities at 4 micrograms/ml. Maltase activities did not decrease with gentamicin. Our data suggest that gentamicin could affect lactase and ALP activities and lower concentration should be used in the culture.     

Effect of gentamycin in combination with prodigiozan on the immunological reactivity of the body

The effect of gentamicin sulphate and its combination will prodigiozan on antibody formation in experiments and the levels of the immunobiologic reactivity of patients with purulent inflammatory processes was studied with a purpose of developing rational schemes of antibiotic therapy of infectious diseases. A decrease in the titers of the antibodies to Aeromonas and the number of antibody-forming cells in the spleen was noted on repeated administration of gentamicin to albino mice in a dose of 20 mg/kg. This was prevented by the use of prodigiozan in a dose of 500 micrograms/kg once every 4 days. The use of gentamicin in patients with purulent inflammatory diseases in doses of 40 or 80 mg twice a day for 7--10 days had no significant effect on the titers of IgA, IgG, IgM, lysozyme blood serum levels, serum bactericidal activity and absorption activity of the peripheral blood neutrophils. Still, it induced a marked suppression of the neutrophil digestive capacity as compared to the initial levels, especially on administration of gentamicin in a dose of 40 mg twice a day. An increase in the level of IgM and no suppression of the neutrophil digestive capacity were noted after completion of the therapy in the patients treated with gentamicin administered in a dose of 40 mg twice a day and prodigiozan administered in a dose of 50 micrograms once every 4 days. It is recommended to use prodigiozan in combinaed therapy with gentamicin for correction of the changes in the specific and nonspecific protective forces of the host.     

Search for inhibitors of West Nile virus among antibiotics]

The activity of 24 antibiotics was studied in treatment of albino mice with experimental encephalitis caused by West Nile virus. The antiviral activity of gentamicin and kanamycin was stated. The survival rate of the animals 19. contaminated with 10-100 LD50 of the West Nile virus and treated parenterally with gentamicin in a dose of 80 to 400 micrograms/mouse was higher than that in the controls by 29.5 to 100 per cent and depended on the drug regimen. The efficacy of kanamycin was lower. The chemotherapeutic indices of gentamicin and kanamycin amounted to 100 and 10, respectively. Since there are no schemes for chemotherapy of the infection caused by the West Nile virus and the respective vaccines are not available the use of the antibiotics and gentamicin in particular appears to be promising in the disease prevention and treatment.     

Sensitivity of the wound microflora of oncological patients to some new antibiotics]

Sensitivity of the microflora of the oncological patients' wounds to the new antibiotics, such as gentamicin, kanamycin, oxacillin, ampicillin and lincomycin was studied with the help of the disc method. The discs with the above antibiotics were prepared under laboratory conditions in accordance with the respective instructions in the WHO. Sensitivity of 429 bacterial cultures, including 98 cultures of pathogenic staphylocci, 45 cultures of Enterococci, 43 hemolytic streptococci, 143 cultures of Escherichia, 50 cultures of Ps. aeruginosa and 50 cultures of Proteus was determined. The studies showed that gentamicin was the most active antibiotic aganist all the microbial species isolated from the surgical and other wounds of oncological patients. It may be used in treatment of the infections caused by association of the microbes belonging to different species, as well as in treatment of purulent processes before elucidating their etiology, 16.7 per cent of the Enterococcal isolates were resistant to gentamicin. Monomycin, kanamycin, oxacillin, lincomycin and macrolide antibiotics at present are sufficiently active against pathogenic staphylococci and hemolytic streptococci.