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At least 19 recordsLinked to original sources
PubMed1976

[Antimicrobial effectiveness of sisomicin. I: In vitro activity of sisomicin compared with gentamicin, tobramycin, amikacin and kanamycin (author's transl)].

The aminoglycosides sisomicin, gentamicin, tobramycin, amikacin and kanamycin are highly active against staphylococci including the penicillinase-positive strains. Sisomicin is more effective than amikacin and kanamycin. Mixed infections with staphylococci and Enterobacteriaceae or Pseudomonas aeruginosa are thus on indication for treatment with sisomicin or other aminoglycosides. Infections with E. coli, Enterobacter, susceptible Klebsiella, and susceptible Pseudomonas strains can be treated with sisomicin, gentamicin or tobramycin. In such cases sisomicin is the most effective antibiotic because of its high antimicrobial activity. In infections with these organisms amikacin can also be used for treatment especially if there is resistance to other aminoglycosides. In hospital-acquired infections with Serratia marcescens amikacin and sisomicin are the drugs of choice. Both aminoglycosides have to be given in high doses in infections with Serratia because of the high inhibitory concentration for Serratia. Sisomicin demonstrates a high antimicrobial activity particularly against indole-positive Proteus species such as Proteus vulgaris and Proteus morganii, Enterobacter, and gentamicin-sensitive Pseudomonas strains. In infections with Pseudomonas aeruginosa tobramycin is the most effective bactericidal antibiotic. Amikacin is the drug of choice against gentamicin-resistant Pseudomonas strains which are also not infrequently resistant to other aminoglycosides. The low proportion of resistance to sisomicin of 7,6% in 370 organisms is only exceeded by amikacin with a rate of 0,6% (resistance to tobramycin 11,4%, gentamicin, 13,2% and kanamycin 42,4%). The low rate of resistance and the high antimicrobial activity are essential advantages of sisomicin.

Amikacin↗
PubMed1978

Semisynthetic aminoglycoside antibacterials. 6. Synthesis of sisomicin, Antibiotic G-52, and novel 6'-substituted analogues of sisomicin from aminoglycoside 66-40C.

The discovery of aminoglycoside 66-40C, a novel dimeric, unsaturated imine produced by Micromonospora inyoensis, afforded a versatile intermediate for the synthesis of a variety of sisomicin analogues modified at the 6' position. The conversion of 66-40C into sisomicin, antibiotic G-52, and a series of novel 6'-substituted analogues of sisomicin is described, and the biological activity of the products is discussed.

Aminoglycosides↗
PubMed1982

[Pharmacokinetics of cefotetan and an aminoglycoside preparation in combined administration. 1. Individual quantification of cefotetan and sisomicin by bioassay and their absorption, distribution, and excretion in rats when given together].

The beta-lactam and aminoglycoside groups of antibiotics are often used in combination. This paper reports a bioassay method for each of cefotetan and sisomicin concentration in body fluids, and pharmacokinetics of both drugs following intravenous administration of cefotetan and intramuscular administration of sisomicin alone and in combination to rats. As to cefotetan determination, a previously reported bioassay method was modified by increasing the NaCl concentration in the sensitivity test agar from 0 to 6%, using Bacillus subtilis ATCC 6633 as the test organism. To assay for sisomicin in the presence of cefotetan, Pseudomonas aeruginosa ATCC 8689, resistant to the beta-lactam antibiotic, was used. Cefotetan (20 mg/kg intravenous) and sisomicin (10 mg/kg intramuscular) were administered concomitantly to rats. The mean plasma concentrations of cefotetan and sisomicin were 16.3 microgram/ml and 16.1 microgram/ml, at 30 minutes after administration respectively. The concentrations were declined to 2.20 microgram/ml for cefotetan and 2.53 microgram/ml for sisomicin at 90 minutes after dosing administration. The calculated plasma half-lives (T 1/2 beta) were 21.3 minutes for cefotetan and 22.2 minutes for sisomicin. The plasma and tissue concentrations of cefotetan administered in combination with sisomicin were nearly the same as those of cefotetan alone. Urinary excretion of cefotetan and sisomicin in the concomitant administration was carried out in rats. Recoveries in urine were 45.9% of the dose for cefotetan and 85.6% of the dose for sisomicin for a period of 24 hours. When each drug was administered alone to rats, cefotetan and sisomicin were recovered 49.8% and 81.6%, respectively, of the dose in the 24-hour urine.

Absorption↗
PubMed1982

[Pharmacokinetics of a cefotetan and an aminoglycoside preparation in combined administration. 2. Absorption and exercise of cefotetan and sisomicin in dogs when the two are given together].

Cefotetan (20 mg/kg i.v.) and sisomicin (10 mg/kg i.m.) were administered alone or in combination to Beagle dogs. The mean plasma concentrations of cefotetan administered in combination with sisomicin at the above dosages were 98.0 microgram/ml at 5 minutes, 45.7 microgram/ml at 30 minutes and 3.46 microgram/ml at 4 hours. These plasma concentrations of cefotetan were similar to those of cefotetan administered alone to the corresponding dogs. The calculated plasma half-lives (T 1/2 beta) of cefotetan were 53.9 minutes in combination with sisomicin and 57.4 minutes alone. The excretion of cefotetan in dog urine were 52.4% and 50.2% of the dose after administration in combination with sisomicin and alone, respectively, during 24 hours. The results indicate that there were no significant differences in the pharmacokinetics of cefotetan alone or in combination with sisomicin in dogs. The maximum concentrations of sisomicin in dogs administered in combination with cefotetan were 20.2 microgram/ml at 30 minutes after dosing. The concentrations of 11.7 microgram/ml at 2 hours and 3.13 microgram/ml at 4 hours of administration were maintained in plasma. The calculated plasma half-lives of sisomicin were 68.8 minutes in combination with cefotetan and 86.4 minutes alone. The urinary rcoveries of sisomicin were 79.3% and 76.1% in combination with cefotetan and alone, respectively, during 24 hours. There were no significant differences in the pharmacokinetics of sisomicin alone and in combination with cefotetan in dogs.

Absorption↗
PubMed1973

Sisomicin: evaluation in vitro and comparison with gentamicin and tobramycin.

Sisomicin is a new antibiotic produced by Micromonospora inyoensis. The in vitro activities of sisomicin, gentamicin, and tobramycin, three similar aminoglycosides, were determined against 228 clinical isolates representing 10 genera of common pathogens. No difference was noted in the activities of these antimicrobial agents when assayed by a standard broth dilution technique against Klebsiella, Enterobacter, Escherichia, Salmonella, Citrobacter, enterococci, or Staphylococcus aureus. Sisomicin was significantly more active than tobramycin against Serratia and indole-positive Proteus strains. Sisomicin was significantly more active than gentamicin against indole-negative Proteus strains and slightly more active against indole-positive Proteus strains. Tobramycin was more active than sisomicin or gentamicin against Pseudomonas and indole-negative Proteus strains. Gram-negative bacilli resistant to one of the three antimicrobial agents were not necessarily resistant to either of the other two. Activity of sisomicin was independent of the susceptibility or resistance of these isolates to nine other antimicrobial agents as assayed by the Bauer-Kirby technique. The presence of 50% human serum did not antagonize the in vitro activity of sisomicin against gram-negative isolates. Because sisomicin showed certain advantages over gentamicin or tobramycin in vitro, further investigation of this new antimicrobial agent is warranted.

Aminoglycosides↗
PubMed1981

Pharmacokinetic study of sisomicin in humans.

Detailed analyses of the pharmacokinetics of sisomicin administered at doses of 25, 50 and 100 mg intravenously and intramuscularly to healthy volunteers established that the drug is handled by a two-compartment open model system with a disposition (elimination) half-life of 2.6 hr. The kinetic estimates over this dose range are linear and independent of dose and were verified by a 60-min infusion experiment in which dose and the maximum serum concentration achieved (5 microgram/ml) were predicted correctly. Sisomicin was rapidly distributed to the tissue compartment, and equilibrium between the central and the tissue compartment was established by 30 min after dosing. Renal clearance (55 ml/min) of sisomicin was about 30% less than total body clearance (78 ml/min). Total urinary excretion of sisomicin during a 24-hr period following drug administration was about 70% of the dose. The disposition kinetics of sisomicin following intramuscular administration are similar to those obtained following rapid intravenous administration. Intramuscular bioavailability of sisomicin for the doses of 25, 50, and 100 mg was greater than 95%. Based on these results, various initial loading infusion doses and maintenance infusion rates were calculated to provide specific desired peak and steady-state serum sisomicin concentrations rapidly. The purpose was not to expose patients to potentially toxic high peak concentrations of drug while maintaining these concentrations during the current therapeutic dosing intervals of 8 to 12 hr.

Biological Availability↗
PubMed1988

Pre-column derivatization of sisomicin with o-phthalaldehyde-beta-mercaptopropionic acid and its application to sensitive high-performance liquid chromatographic determination with fluorimetric detection.

The stability of the o-phthalaldehyde (OPA) derivatives of sisomicin obtained using beta-mercaptopropionic acid was investigated by reversed-phase high-performance liquid chromatography. One of the fluorescent derivatives of sisomicin was stable at least for 6 h in 50% methanol under the optimal conditions used (OPA concentration, pH and temperature). When plasma samples spiked with sisomicin were analysed, the response was linear in the calibration range 136-900 pg of sisomicin per injected volume (40 microliters). As little as 0.06 micrograms of sisomicin per 1 ml of plasma could be detected with signal-to-noise ratio greater than or equal to 2. For plasma samples spiked with 0.2 micrograms/ml sisomicin, the recovery was 97.1 +/- 6.6% (mean +/- S.D., n = 5) with a within-run coefficient of variation of 6.8% and a day-to-day coefficient of variation of 7.2%. The method was also applied to plasma samples from rabbit after a subcutaneous injection of 1 mg/kg sisomicin.

3-Mercaptopropionic Acid↗
PubMed1976

[Sisomicin versus gentamicin. A comparison of antibacterial and pharmacokinetic properties (author's transl)].

In a comparison of the antibacterial in-vitro activity of sisomicin, gentamicin, and tobramycine, sisomicin showed a higher activity against E. coli, indole-positive Proteus spp. and organisms of the Klebsiella-Enterobacter-Serratia group, whereas tobramycine was superior against Pseudomonas spp. However, the differences in activity between sisomicin and gentamicin were only within one step of dilution which is hardly sufficient to guarantee a basic superiority of one or the other preparation for clinical purposes. In 12 healthy probands serum levels and renal elimination of sisomicin and gentamicin after a single intramuscular injection of 1 mg/kg body weight were investigated in a randomised change-over trial. With corresponding serum levels, almost identical elimination half-lives of 109 and 111 minutes, and recovery values of 84 and 88.4%, respectively, there were no significant differences in the pharmacokinetics of sisomicin and gentamicin. Thus in the antibacterial treatment of gentamicin-sensitive gram-negative organisms sisomicin presents an equally good alternative. With organisms only moderately sensitive or resistant to gentamicin, sisomicin, tobramycine and amikacin should be additionally tested.

Anti-Bacterial Agents↗
PubMed1985

[Decrease of sisomicin nephrotoxicity as affected by cephalothin: pharmacokinetic evaluation].

The effect of cephalothin on the nephrotoxicity and pharmacokinetics of sisomicin was studied on Wistar rats. Sisomicin was injected intramuscularly in doses of 12.5 and 25 mg/kg alone or in combination with cephalothin in a dose of 360 mg/kg once a day for 16 days. It was shown that the combined use of sisomicin and cephalothin resulted in less pronounced functional and morphological changes in the kidneys as compared to the use of sisomicin alone. The decrease in the nephrotoxic effect was accompanied by a decrease in the sisomicin concentration in the blood serum and the site of the nephrotoxic effect (the kidney cortical layer) and the period of the aminoglycoside half-life in the kidney cortical layer under the action of cephalothin. The analysis of the relation between the nephrotoxic effect and the concentration of sisomicin in the kidney cortical layer and blood serum demonstrates that the nephrotoxicity of the sisomicin combination with cephalothin is mainly due to a decrease in the aminoglycoside concentration in the zone of the nephrotoxic effect.

Animals↗
PubMed1978

[Pharmacokinetic investigations on sisomicin in children (author's transl)].

Sisomicin is an aminoglycoside effective against gramnegative germs. The sensitiveness of coli, proteus, pseudomonas and klebsiella ranges from 0,1 to 0,4 mcg/ml. Germs with inhibition-values of up to 1 mcg/ml are certainly Sisomicin-sensitive. The side-effects of Sisomicin resemble those of other aminoglycosides, as for instance lesions of the VIIth cranial nerve and the kidney. Since aminoglycosides have a relatively small therapeutic range between toxicity and effective minimal-concentration, investigations are important especially in children. 66 children of different age groups received Sisomicin in doses of 3 mg/kg, 2 mg/kg and 1 mg/kg, and examined pharmacokineticly. Serum-levels were measured after 30 min 1, 2, and 4h, in some cases also after 6 and 8 h. In a separate group we determined the values after 5, 10, 15, 20, 30 and 40 min. The urinary output was controlled and the content of Sisomicin in meconium determined. Based on these results we recommend an individual, Sisomicin dosage for each age group. Clinically the Sisomicin proved to be well tolerated and effective antibioticum.

Age Factors↗
PubMed1976

Pharmacokinetics of sisomicin in patients with normal and impaired renal function; its efficacy in urinary tract infection.

Serum concentration, biological half-life, distribution space and serum clearance of sisomicin, a new aminoglycoside antibiotic, have been studied in twenty-three patients in comparison with the pharmacokinetics of 125I-labelled iothalamate, a compound only filtered by the kidney. 10 patients had normal or borderline abnormal serum creatinine (less than 1,5 mg/100 ml), 8 had various degrees of renal insufficiency (serum creatinine 1.7-9.6 mg/100 ml) and 6 were being treated by intermittent haemodialysis. After intravenous injection of sisomicin 1 mg/kg body weight in patients with normal or borderline renal function its half-life was 3.5 h, very similar to that of iothalamate, 3.2 h. The mean distribution space was 20.1% per cent of body weight; iothalamate, 23.7%. In patients with renal insufficiency there was a positive correlation between serum creatinine level and the half-life of sisomicin, and an even stronger correlation between the clearances of iothalamate and sisomicin. In patients dependent on haemodialysis, the mean serum half-life between dialysis was 40 h, compared to approximately 100 hours for iothalamate, which implies additional extrarenal clearance or tubular secretion of sisomicin. The results of pharmacokinetic studies indicated that a regime of sisomicin 1 mg/kg every 8 to 12 hours in patients with normal renal function would result in serum and urine levels sufficiently high to treat most urinary tract infections. In patients with impaired renal function the dosage interval should be increased according to the serum creatinine level, and in patients dependent on haemodialysis one standard dose at the end of each dialysis period should suffice. 9 patients with a chronic urinary tract infection severely complicated by an underlying disease were treated according to this dosage regimen with a satisfactory bacteriological and clinical result. No adverse reactions or signs of accumulation were observed.

Adult↗
PubMed1979

[Experience with sisomicin in pediatrics (author's transl)].

Sisomicin, an aminoglycoside antibiotic, is especially effective against Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Serratia, indole-positive and indole-negative Proteus species, Pseudomonas aeruginosa, Salmonella and Staphylococcus aureus. It has a bactericidal action. Although sisomicin is similar to the other aminoglycoside antibiotics, there is not complete cross-resistance to them. Our own pharmacokinetic investigations showed that a dose of 2--3 mg/kg body weight of sisomicin twice daily is necessary in the neonatal period. Infants should be given 2.5 mg/kg body weight three times daily, and school children 1.5--20 mg/kg body weight, likewise three times daily. Excretion of sisomicin in the urine is lower in children than in adults, amounting within 24 hours to only 10--20% in newborns, and 30--40% in school-children. Sisomicin induces excretion of some enzymes in higher quantities from the tubular part of the kidneys, especially alaninaminopeptidase. A report is given on 58 patients, especially newborns and prematures, who were treated for about seven days with sisomicin. The results obtained with a wide variety of infections (such as omphalitis, aspiration of amniotic fluid with broncho-pneumonia, phlegmons of the galea, and also pyelonephritis and mucoviscidosis with pulmonary complications) can be described as good, with a success rate of 85%. On only seven occasions were insignificant transitory side-effects, such as slight increase in transaminases, toxic-allergic exanthema and pain in the region in injection, observed.

Age Factors↗
PubMedDate not supplied

Sisomicin: a review of eight years' experience.

Sisomicin is a new broad-spectrum aminoglycoside most closely related structurally to gentamicin C1a. In vitro and in experimental infections, sisomicin has been found to be more potent than or nearly as potent as the most active of the other available aminoglycosides. Although susceptible to many (but not all) aminoglycoside-inactivating enzymes, sisomicin is active against many microorganisms that are resistant to other aminoglycosides by nonenzymatic mechanisms. Sisomicin has been shown to interact synergistically with various beta-lactam antibiotics against enterococci, staphylocicci, Enterobacteriaceae, and nonfermentative gram-negative bacilli. The pharmacokinetics and toxicity of sisomicin in humans appear to be similar to those of gentamicin, despite earlier reports of greater acute toxicity in animals. Sisomicin has been shown to be effective for treatment of severe infections in humans, including some infections caused by gentamicin-resistant bacteria.

Animals↗
PubMed1978

Experimental osteomyelitis. V. Therapeutic trials with oxacillin and sisomicin alone and in combination.

Oxacillin was used alone and in combination with sisomicin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Within diseased bone, levels of oxacillin and sisomicin remained higher than the minimal inhibitory concentration for 2 and 6 hr, respectively, after injection of 50 mg of oxacillin/kg and 10 mg of sisomicin/kg. Treatment with 50 mg of oxacillin/kg four times daily or 50 mg/kg every 4 hr around the clock for 28 days sterilized 30% of the rabbit bones. Sisomicin (10 mg/kg) injected twice daily for 28 days sterilized only 5% of the rabbit bones. In contrast, treatment with the combination of oxacillin and sisomicin for either 14 or 28 days was significantly more effective, sterilizing 78% and 85%, respectively, of the bones of treated animals. S. Aureus isolated from bones of animals treated with sisomicin alone contained aminoglycoside-resistant microcolonies. Resistant microcolonies were not recovered from animals treated with oxacillin or with the combination of oxacillin plus sisomicin. In vitro studies of bacterial killing by each antibiotic alone and in combination showed more bacterial killing with the combination than with either agent alone; in vitro the combination prevented emergence of resistant microcolonies. Combination antibiotic therapy appears to be more effective in treatment of experimental osteomyelitis due to S. aureus than therapy with a single agent.

Animals↗
PubMed1998

Analysis of sisomicin binding sites in Micromonospora inyoensis cell wall.

Sisomicin binding sites are located in the cell wall. They are the carboxyl groups of peptidoglycans, which are major components of the cell wall. The carboxyl groups have negative charges which can bind the positively charged amino groups of sisomicin. When the negative charges of the carboxyl groups of the peptidoglycans are changed to neutral or positive charges, sisomicin does not bind to the cell wall. Magnesium ions bind to the cell wall in competition with sisomicin, and have a weak affinity for the cell wall binding sites compared with sisomicin. The binding molar ratio of sisomicin to magnesium ions was approximately 1 to 10.

Anti-Bacterial Agents↗
PubMed1976

Clinical pharmacokinetics of sisomicin: dosage schedules in renal-impaired patients.

The pharmacokinetics of intravenously administered sisomicin were studied in 33 patients with normal renal function and different degrees of renal impairment. In all patients, the serum disappearance of sisomicin, once distribution equilibrium had been achieved, followed first-order kinetics and percentage of hourly loss from serum decreased proportionally with decreasing renal function. Half-lives averaged 2.06 h in normal subjects (endogenous creatinine clearance greater than 80 ml/min per 1.73 m(2)) and reached 35.3 h in a virtually anephric subject. Linear relationships were defined between sisomicin serum half-life and the reciprocal of the endogenous creatinine clearance and serum creatinine concentration. The latter relationship indicates that the half-life of sisomicin may be approximated as twice the serum creatinine concentration and may be used for dosage adjustment in renal-impaired patients. Prediction of the extent of sisomicin removal by hemodialysis may be made from the relationship between the dialyzate of sisomicin and that of creatinine and blood urea nitrogen. Dosage schedules and methods of administration compatible with the pharmacokinetic properties of the antibiotic are finally proposed.

Adult↗
PubMed1979

In vitro sensitivity of Proteus organisms to gentamicin and sisomicin.

The antibacterial activity of gentamicin and sisomicin was studied in 148 recent clinical isolates of Proteus obtained from patients hospitalized in Athens. Both gentamicin and sisomicin were found to be active with sisomicin generally being the more active of the two; P. mirabilis strains were less susceptible than the indole-positive strains, but P. mirabilis organisms isolated from the respiratory tract were more sensitive to sisomicin than those isolated from the urine. Susceptibility testing with the two aminoglycoside antibiotics was affected by inoculum size and by the test broth used. Sisomicin sensitivity testing with the disc-agar diffusion method and broth dilution method was reliable for the indole-positive strains of Proteus but did not separate all sensitive from resistant strains of P. mirabilis. An in vitro synergism was demonstrated between sisomicin and the semisynthetic penicillin, ticarcillin.

Bacteriuria↗