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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↗

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↗

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↗

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↗

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↗

PubMed1978

Sisomicin: in vitro activity and pharmacokinetics.

In vitro activity of sisomicin and gentamicin was compared in serial dilution tests for 619 bacterial strains (Staphylococcus aureus, E. coli, Proteus mirabilis, Proteus vulgaris, Enterobacter, Klebsiella, Pseudomonas aeruginosa, Salmonella, Serratia marcescens). Mean MIC of sisomicin was lower by one geometrical dilution step compared with gentamicin for Pseudomonas, Proteus vulgaris, Klebsiella, and Serratia, while it was almost identical with the other species. Resistance (MIC greater than 5 microgram/ml) against sisomicin was observed in 2% of Pseudomonas strains, resistance against gentamicin in 8%. Ten healthy adult volunteers had serum peak levels (after i,m. injection of 40 mg and 80 mg sisomicin) of 2.7 and 3.2 microgram/ml. Urine recovery (in 24 hrs) was 76%. Continuous i.v. infusion of sisomicin or gentamicin (6.6 mg/hour in 7 healthy adult volunteers) yielded in serum levels of 0.64 and 1.03 microgram/ml respectively. Biological half-life (90 minutes), urine recovery (60% in the fourth hour), renal clearance and skin blister levels at the end of infusion were almost identical for both antibiotics; total clearance was somewhat higher with sisomicin than with gentamicin.

Adult↗

PubMedDate not supplied

A comparative trial of sisomicin therapy by intermittent versus continuous infusion.

One hundred and thirty-nine febrile episodes in 120 patients were treated with sisomicin after a combination of carbenicillin and a cephalosporin antibiotic had failed. These patients were randomized to receive sisomicin either by continuous or by intermittent infusion. The response rate for patients treated with sisomicin was 61 percent by continuous infusion and 46 percent by intermittent infusion, which was not statistically significant. Pneumonia, septicemia, and soft tissue infections were the most frequent infections. Most (96 percent) of the identified pathogens were gram-negative bacilli with the most frequent being Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. The response rate was higher in those patients whose neutrophil count increased or remained the same while on therapy. The worst response was obtained if there was a decrease in the neutrophil count during therapy. The major toxicity of sisomicin was found to be azotemia and occurred in 17 percent of episodes treated by continuous infusion and in 21 percent treated by intermittent infusion. Hearing loss in the high frequency range occurred in five patients. Sisomicin is effective in the treatment of gram negative infections in neutropenic cancer patients.

Adolescent↗

PubMed1976

Micromonospora-produced sisomicin components.

A sisomicin fermentation carried out in the presence of (methyl-14C)-L-methionine resulted in a crude mixture, composed of methyl-14C-labeled sisomicin as a major component; and two 4''-C-desmethylsisomicin (66-40B and 66-40D) isomer-like components, an unidentified component and a gentamicin A-like antibiotic as minor components. When (methyl-14C)-L-methionine was added in an early stage of the fermentation (24 hours), incorporation of methyl-14C-label into polar components (e.g., gentamicin A-like antibiotic) preceded that into sisomicin. Chromatographic evidence for the bioconversion of (methyl-14C)-gentamicin A to a radioactive sisomicin-like product (possibly (3''-N-methyl-14C)-sisomicin) was seen, when a Micromonospora blocked mutant was incubated in the presence of the former antibiotic.

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↗

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↗

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↗