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PubMed1983

[Pharmacokinetic prediction of the efficacy of using sisomicin in wound infections].

The pharmacokinetics of sisomicin in the blood, infection foci and urine of patients with wound infections was studied comparatively. Higher blood levels of the antibiotic after intravenous injection as compared to those after intramuscular injection provided its more intensive penetration into the tissues of the wound edges and bottom. After intravenous injection the sisomicin concentration in the tissues was sufficient for inhibition of the strains of Staphylococcus, E. coli and Ps. aeruginosa detected in the patients, while after intramuscular injection the antibiotic levels were sufficient only for inhibition of the first two causative agents. Comparison of the data on the sisomicin pharmacokinetics in the blood and tissues of the wounds provided the characteristics of the level of the drug penetration into the focus of the infection ("therapeutic availability"). Since the levels of sisomicin in the blood and infection foci were highly variable in different individuals. It is recommended that the antibiotic be used under the control of its concentrations in patients. It was shown that the data on the sisomicin renal excretion might be used for the purposes of the pharmacokinetic control.

Humans↗
PubMed1980

Data on sisomicin effect: human pharmacokinetic and bacteriological studies.

Antibiotic sensitivity of bacteria cultured from 1020 pulmonological, medical and surgical cases was determined. Inhibitory effect on the bacterial growth was observed most frequently with sisomicin among the antibiotics of aminoglycoside type. Sisomicin levels were studied in the serum and lung tissue in 20 cases of pulmonary operations. Fifty to ninety minutes subsequent to an intramuscular administration of 1 mg sisomicin per 1 kg body weight, the serum levels amounted to 4.0 mcg/ml, whereas the apparently healthy, the inflamed and tumourous parts of the removed lung tissue contained 2.2, 1.2 and 0.2 mcg/g. The serum level remained unchanged even after 110-150 min, when the lung tissue levels were 3.0, 1.5 and 2.1 mcg/g. The sisomicin concentrations found in the lung tissue are of bactericid effect only against a part of the bacteria studied. This fact emphasizes the importance of exact indication and use of doses of sisomicin.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparative study of three routes of administration of sisomicin.

A comparative study was performed using three routes of administration of sisomicin (1 mg/kg as single dose): intramuscular injection, intravenous rapid injection, and 1-hour infusion. Intravenous administration resulted in higher blood levels immediately after the injections than by the intramuscular route; however, later, the intramuscular injection resulted in optimal blood levels. High levels of sisomicin which were bactericidal for most Gram-negative bacilli were found in the urine of the treated patients. The antimicrobial activity of the serum obtained 1 hour after administration of sisomicin, as determined against 20 strains of Gram-negative microorganisms isolated from blood cultures, was identical with all three routes of administration of sisomicin.

Adult↗
PubMed1989

Determination of the aminoglycoside antibiotics sisomicin and netilmicin in dried blood spots on filter discs, by high-performance liquid chromatography with pre-column derivatization and fluorimetric detection.

A simple method for the determination of the aminoglycoside antibiotic sisomicin or its 1-N-ethyl derivative, netilmicin in whole blood, using dried blood spots (DBSs) on filter-paper punched discs has been developed. Sisomicin or netilmicin in the DBSs were recovered most effectively in 0.5 M Na2HPO4 using ultrasonication. The eluates from the DBSs were treated by ultrafiltration for deproteinization and subjected to pre-column fluorescent derivatization using o-phthalaldehyde and beta-mercaptopropionic acid in 0.05 M KH2PO4-borate buffer (pH 9.0), followed by determination by reversed-phase high-performance liquid chromatography. The detection limits of sisomicin and netilmicin in the DBSs on punched discs (10.1 microliters of whole blood) were 0.053 and 0.50 micrograms per ml of whole blood, respectively (signal-to-noise ratio greater than or equal to 2). The method permits a simple collection of blood at the microlitre level and should prove particularly useful for monitoring sisomicin and netilmicin in blood at therapeutic levels in geriatric and paediatric patients.

Chemical Phenomena↗
PubMed1992

Aqueous kinetics of sisomicin sulphate.

Sisomicin sulphate is a new-generation aminoglycoside with a broad spectrum of antimicrobial activity that includes Pseudomonas aeruginosa. It is superior to gentamicin against indole-negative Proteus and some resistant strains of Pseudomonas. The ocular pharmacokinetics of sisomicin have not been explored. We used the agar diffusion technique of microbial assay to determine the aqueous penetration and bioavailability of a subconjunctivally placed standard dose of 20 mg/0.4 ml of sisomicin sulphate in 20 human volunteers undergoing elective cataract surgery. A peak concentration of 16.4 mg/l was found in the aqueous humour 78 minutes after injection, which is 65 times the minimum inhibitory concentration for Pseudomonas. The antibiotic was bioavailable up to 1203 minutes after injection in a concentration of 0.9 mg/l, which easily covers the minimum inhibitory concentration of Staphylococcus aureus and Pseudomonas. The antibiotic disappears from the aqueous humour at the 1434 minute interval (approximately 24 hours). The elimination half-life (t1/2 of sisomicin was determined to be 5.16 hours (K = 0.134/hour) and the aqueous clearance was 2.87 microliters/min.

Aqueous Humor↗
PubMed1976

Persistence of sisomicin and gentamicin in renal cortex and medulla compared with other organs and serum of rats.

Aminoglycoside antibiotics seem to accumulate and persist in the kidney. For a better understanding of this problem, groups of six rats received a single 4 mg/kg i.p. injection of sisomicin and were sacrificed repeatedly from 30 min to 28 days later. Sisomicin concentrations (bioassay) decreased rapidly in the serum, lung and other tissues. There was only a trace at six hours. The situation was totally different for the kidney. Concentrations in the cortex increased up to six hours with a maximum of 99 mug/g, 11 times higher than the peak value in the serum then decreased very slowly to 56, 18, and 7 mug/g, 2, 14 and 28 days, respecitvely, after injection. The concentrations in the medulla were lower than in the cortex but also showed an accumulation and persistence. Similar results were observed with gentamicin. In another experiment, daily injections of sisomicin or gentamicin during seven days demonstrated that the concentrations of both antibiotics six hours after the last injection were nearly three times higher in the cortex and twice as high in the medulla than after a single injection. These data explain why the nephrotoxicity of sisomicin or gentamicin involves chiefly the cortex, increases with the length of the treatment and can persist for several weeks after the last injection. Therapeutic implications need further studies.

Animals↗
PubMed1975

Experimental osteomyelitis. IV. Therapeutic trials with rifampin alone and in combination with gentamicin, sisomicin, and cephalothin.

Levels of rifampin, gentamicin, sisomicin, and cephalothin in normal and osteomyelitic rabbit bones were measured, and the efficacy of these drugs in the treatment of osteomyelitis was evaluated. Single drug regimens, including rifampin for 14 days and gentamicin, sisomicin, and cephalothin each for 28 days, were relatively ineffective (5%-33% sterile bone cultures). Rifampin, administered for 28 days, sterilized the bones of 55% of treated animals. The combination of gentamicin and rifampin, given for either 14 or 28 days, sterilized the bones of 67% of treated animals. The combinations of rifampin plus sisomicin and of rifampin plus cephalothin, given for 28 days, were significantly more effective than these agents alone, sterilizing 90%-95% of bones. The combination of rifampin, sisomicin, and cephalothin, given for only 14 days, sterilized the bones of all treated rabbits. Staphylococci isolated from the bones of therapeutic failures that had received rifampin alone or in combination with other antibiotics were highly resistant to rifampin (minimal inhibitory concentration, greater than 250 mug/ml), whereas the organisms recovered from animals not receiving rifampin remained sensitive. Results of in vitro studies of synergy and/or bactericidal activity of antibiotic combinations correlated with in vivo results in some, but not all, instances.

Animals↗
PubMed1976

Pharmacokinetic parameters of sisomicin.

Sisomicin in doses of 1 mg/kg was administered intramuscularly to 10 healthy volunteers, and 1 week later the same volunteers received sisomicin at the same dose intravenously. A peak serum concentration of sisomicin of 3.08 mug/ml was obtained 1 h after intramuscular injection, and a peak serum concentration of 7.12 mug/ml was achieved 30 min after a 30-min intravenous infusion. The sisomicin elimination data were analyzed according to a two-compartment model. Pharmacokinetic parameters derived from the intramuscular and intravenous studies were quite similar.

Adult↗
PubMed1976

Radioimmunoassay of sisomicin.

An antibody induced in rabbits against a gentamicin-bovine serum albumin conjugate cross-reacted with the chemically related aminoglycoside, sisomicin, facilitating the development of a sisomicin radioimmunoassay. Sisomicin was labeled with (125)I using an acylating agent [3-(4-hydroxyphenyl)propionic acid-N-hydroxy-succinimide ester]. The resulting assay produced a linear standard curve on a logit-log plot with a sensitivity of 140 pg. Comparison with a microbiological assay showed no significant difference (P < 0.001) in the measurement of sisomicin by these two methods.

Animals↗
PubMed1978

In vitro activity of sisomicin and netilmicin alone and in combination with nafcillin, oxacillin and methicillin against enterococci.

The in vitro activity of sisomicin and netilmicin alone and in combination with nafcillin, oxacillin and methicillin against 30 strains of enterococci was investigated. Sisomicin and netilmicin alone were not very effective against enterococci. There was enhanced killing of some strains of enterococci by the combination of sisomicin or netilmicin with one of the three penicillinase-resistant penicillins. Nafcillin was the most effective penicillinase-resistant penicillin in the combination. Sisomicin appeared to be slightly more effective than netilmicin in combination with one of the penicillinase-resistant penicillins against enterococci.

Drug Synergism↗
PubMed1978

Chemical modification of some gentamicins and sisomicin at the 3''-position.

Chemical and photochemical oxidative methods of de-N-methylation of some gentamicins and sisomicins at the 3''-position are described. Selective acetylation of gentamicins and sisomicins at the 1, 3, 2' and 6' and of gentamicin B at the 1, 3, and 6'positions are achieved by treatment of the free bases with carbon dioxide prior to acetylation. De-N-methylation of the above selectively blocked gentamicins and sisomicins followed by re-alkylation at the 3''-position and de-N-protection gives a series of 3''-N-alkyl analogues. The in vitro antibacterial properties of the new derivatives of gentamicins and sisomicins are given.

Acetylation↗
PubMed1992

[Antibiotics of the aminoglycoside group (gentamicin, sisomicin and amikacin) in the prevention and treatment of experimental plague].

Activity of aminoglycosides such as gentamicin, sisomicin and amikacin against plague microbe strains of natural origin was studied in vitro. It was also studied in prophylaxis and treatment of experimental plague infection in albino mice. The MAC of gentamicin and sisomicin for 50 strains of the plague microbe was 0.2-1.6 micrograms/ml. For the majority of the strains it was 0.4 micrograms/ml. The amikacin MICs were 0.4-3.2 and 0.8 micrograms/ml, respectively. High efficacy of gentamicin, sisomicin and amikacin was shown in prophylaxis and treatment of experimental plague infection in albino mice. The optimal doses of the antibiotics were determined. Under definite conditions such as the use of short-term regimens and higher intervals, advantages of sisomicin over gentamicin and amikacin in prophylaxis of experimental plague infection were observed.

Amikacin↗
PubMed2005

[Study on cloning of sisomicin-resistant gene (sisR) from Micromonospora inyoensis].

A new sisomicin resistance gene sisR was cloned from sisomicin-producing Micromonospora inyoensis. The sisR fragment was obtained by PCR amplification. The primer pairs were designed based on grm gene sequence from gentamicin-producing Micromonospora purpurea. The template DNA was isolated from Micromonospora inyoensis. A series of different DNA fragments were amplified by PCR, which were sub-cloned to vector pUC19 for further identification. It was found that five specific transformants containing target DNA fragments could resist high concentrations of sisomicin (over 1000 microg/mL sisomicin). One of them designated as sisR, was then sequenced and the alignment among sisR and other related genes showed that sisR gene differs from any known genes. It was concluded that sisR gene is a sequence that has not been reported so far.

Anti-Bacterial Agents↗
PubMed1978

[Clinical, bacteriological and pharmacokinetic study of Sisomicin in the newborn infant].

A study of the efficiency and tolerance of sisomicin in 19 children with severe bacterial infections led to the following conclusions: -sisomicin was efficient, particularly in association with beta-lactamin; -the local and systemic tolerance was good. The susceptibility of various bacterial strains was studied. The half-life of sisomicin given intramuscularly was : 4,0 +/- 1,8 hours in the new-borns under 10 days and 2,0 +/- 0,3 hours in older infants, when creatininemia was below 10 mg/l. No accumulation was found. The recommended daily dose of sisomicin by intramuscular route is 3 to 6 mg/kg, i.e. 1 to 2 mg every 8 hours in infants an 1,5 to 3 mg every 12 hours in new-borns.

Bacterial Infections↗
PubMed1989

In vitro comparative activity of kanamycin, gentamicin and sisomicin--a new aminoglycoside, against clinical isolates.

540 strains of bacteria isolated from various clinical materials comprising 440 strains of Gram negative bacilli and 100 strains of Gram positive cocci were tested for their susceptibility in vitro to Kanamycin, Gentamicin and a new aminoglycoside antibiotic Sisomicin (Ensamycin). The sensitivity pattern revealed that 68.88% of the strains were sensitive to Kanamycin, 82.9% to Gentamicin and 89.0% to Sisomicin. The effectiveness of Sisomicin is comparatively greater (6.1%) than the other two aminoglycosides. In particular a considerable number of Gentamicin resistant Pseudomonas aeruginosa (12.3%) were found to be sensitive to Sisomicin which is a highly desirable property. Existence of about 11% Sisomium resistant strains even before the wide usage of this antibiotic is note worthy.

Drug Resistance, Microbial↗
PubMedDate not supplied

["In vitro" activity of gentamicin, sisomicin and tobramycin against "pseudomonas aeruginosa" strains from hospital sources (author's transl)].

The in vitro activity of two amynoglicosidic antibiotics, tobramycin and sisomicin, against 215 strains of Pseudomonas aeruginosa isolated from clinical specimens during the years 1972-1975, was evaluated in comparison with that of gentamicin. Tobramycin showed a greater activity than sisomicin and gentamicin. At the concentration of 5 mu/ml tobramycin resulted inhibitory on 94% of strains and sisomicin and gentamicin on 78.6% and 49.8% of strains respectively. The susceptibility of Pseudomonas aeruginosa strains to gentamicin decreased from 1972 to 1975, with an increasing of resistant strains of 23%. In an evaluation of possible cross-resistance of 14 strains of Pseudomonas aeruginosa highly resistant (MIC greater than or equal to 25 gamma/ml) to gentamicin, 13 showed a high degree of resistance also to sisomicin; on the other hand 7 strains highly resistant to gentamicin was sensitive to tobramycin at concentration less than or equal to 10 gamma/ml.

Anti-Bacterial Agents↗
PubMed1981

Prospective double-blind controlled clinical study of sisomicin versus tobramycin.

A double-blind controlled trial was carried out to compare the efficacy of sisomicin and tobramycin in the treatment of 55 hospitalized patients with serious systemic infections, mostly intra-abdominal or soft-tissue infections. Each drug was administered intramuscularly or intravenously at a dosage of 2.5 to 4.0 mg/kg per day for between 5 and 21 days. At the end of treatment, 22 (79%) of 28 sisomicin-treated patients and 15 (72%) of 21 tobramycin-treated patients were assessed, on the basis of clinical and bacteriological response, as cured or partially cured. Sisomicin was superior in the treatment of Escherichia coli infections. Local tolerance to both drugs was good. The incidence of systemic adverse reactions was low, fewer cases occurring in the sisomicin treatment group than in the tobramycin treatment group.

Anti-Bacterial Agents↗
PubMed1981

Comparative clinical trial of sisomicin and gentamicin in serious systemic gram-negative infections.

One hundred one hospitalized patients with serious gram-negative infections were treated with either sisomicin, 1.0 mg/kg every eight hours, or gentamicin, 1.5 mg/kg every eight hours, in a multicenter study conducted at ten separate locations in the United States. Since the drugs were administered at different dosages, a blinded investigator was employed to assess treatment response, while an unblinded investigator was responsible for making dosage adjustments based on each patient's renal function and clinical response. Sixty of the patients (sisomicin, 29; gentamicin, 31) were treated for a sufficient period (average seven to ten days) to be valid for inclusion in the assessment of treatment efficacy; 81 were included in the safety analysis. Sisomicin was found to be superior to gentamicin in bacteriological response and slightly better than gentamicin in producing favorable clinical responses. Elimination of pathogens or a significant reduction in pathogen population was observed in 93% of the sisomicin-treated patients, compared with 67% in the gentamicin group (P = 0.06). The incidence of adverse effects in both treatment groups was low, with no significant differences in adverse reaction patterns.

Bacterial Infections↗