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PubMed1975

In vitro activity of sisomicin, an aminoglycoside antibiotic, against clinical isolates.

Sisomicin, a new aminoglycoside antibiotic which is produced by Micromonospora myoensis, was studied against 565 clinical isolates of gram-negative bacilli and gram-positive cocci. With the exception of Serratia marcescens, over 90% of isolates of gram-negative bacilli were inhibited by 1.56 mug/ml or less of sisomicin. Sisomicin was slightly more active than gentamicin and tobramycin aganist isolates of Escherichia coli, Proteus mirabilis and Klebsiella spp. It was substantially more active than butirosin and kanamycin against all gram-negative bacilli. Isolates of gram-negative bacilli which were resistant to gentamicin and tobramycin were also resistant to sisomicin. Most of these isolates were sensitive to amikacin.

Aminoglycosides↗
PubMed1982

Gentamicin and sisomicin - induced renal tubular damage.

Early signs of aminoglycoside - induced renal tubular damage were detected in 26 patients given gentamicin and 23 given sisomicin. The urinary elimination of 3 low molecular weight proteins (LMWP) - beta 2 microglobulin, retinol binding protein and lysozyme (LZM), and the urinary activity of 2 enzymes - alanine aminopeptidase and N-acetyl-beta-glucosaminidase - was measured before, during and after treatment. In gentamicin - treated patients LMWP elimination increased, especially LZM which rose markedly during treatment and returned to normal values after its end. Enzyme activities also rose while gentamicin was being given. Sisomicin produced smaller changes. As neither the mean serum creatinine nor the mean urinary elimination of transferrin were increased, glomerular function was probably not affected. However, tubular damage was detected, as shown by the LMWP output (especially LZM) and increased enzyme activity. Urinary LMWP and enzyme measurements are presented as sensitive and reliable methods to monitor early aminoglycoside - induced tubular impairment. It is suggested that the different renal toxicities of gentamicin and sisomicin are related to differences in their accumulation in the renal cortex.

Acetylglucosaminidase↗
PubMed1982

Pharmacokinetic studies of azlocillin, mezlocillin, cephalothin and sisomicin in rabbits.

Pharmacokinetic parameters of two new acylureido penicillins (azlocillin and mezlocillin) and of cephalothin and sisomicin were compared in rabbits after the subcutaneous administration of 50 mg or 100 mg. It was found that the highest serum level of the antibiotics was reached 15 to 30 min after administration. Only sisomicin, applied in a higher dosage, reached its peak value after 60 min. The half-lives for azlocillin and mezlocillin were 1.35 h and 1.38 h, respectively. The half-lives for cephalothin and sisomicin were 0.65 h and 5.7 h, respectively.

Animals↗
PubMed1975

Treatment with sisomicin of complicated urinary tract infections in patients with varying degrees of renal function impairment, pharmacokinetics and dosage adjustment.

The efficacy, tolerance and pharmacokinetics of the new aminoglycoside antibiotic sisomicin, have been studied in 29 elderly male patients with varying degrees of renal function impairment and suffering from complicated urinary tract infections. The antibiotic was equally effective in patients with normal and impaired renal function and a cure (negative urine culture at one week follow-up) of 56% was obtained. There was little apparent toxicity with the dosage regimens used, although serum creatinine values were statistically but not clinically significantly increased in some patients following treatment. Serum half-lives of sisomicin were prolonged in cases of impaired renal function but accumulation of antibiotic could be prevented by varying dosing intervals between 8 and 24 hours based on serum creatinine values. There was good correlation between serum creatinine and sisomicin serum half-life values and a practical method is described for dose adjustment based on the relationship between serum half-lives and serum creatinine concentrations.

Aged↗
PubMed1977

Treatment of complicated urinary tract infections. Comparative study of sisomicin and gentamicin.

The efficacy and safety of the two aminoglycoside antibiotics, sisomicin and gentamicin, were investigated in a prospective randomized study of 100 elderly male patients with complicated urinary tract infections. Both drugs were administered intramuscularly, sisomicin twice daily and gentamicin three times daily according to body weight. All bacteria isolated from the urine were sensitive to both antibiotics by disk sensitivity method. Seventy per cent of the patients treated with sisomicn and 63 per cent of those treated with gentamicin were cured of infection. There was no apparent toxicity noted from either drug. The twice daily sisomicin administration appeared to be as effective and safe as the three times daily administration of gentamicin in the treatment of complicated urinary tract infections.

Anti-Bacterial Agents↗
PubMed1986

The International Standard for sisomicin.

An International Standard for Sisomicin has been established on the basis of a collaborative assay. There were seven participating laboratories in seven countries. The activity of the contents of each ampoule of the International Standard of Sisomicin is defined as 35,200 International Units of Sisomicin.

Humans↗
PubMed1983

In vitro and in vivo effect of sisomicin and gentamycin on polymorphonuclear chemotaxis and phagocytosis.

Ten patients with acute bacterial infections were studied to demonstrate the influence of two aminoglycosides, sisomicin and gentamycin on polymorphonuclear (PMN) chemotactic and phagocytic functions. Five of these subjects were treated with gentamycin and five with sisomicin both at a dosage of 2.5 mg kg-1 day-1. The assays were performed before and after 5 days of therapy. Before beginning treatment, the in vitro action of the aminoglycoside antibiotics (20 micrograms ml-1) was also tested. Granulocytes from 8 healthy people were used as controls. After therapy, no significant difference in basic values was found in either the gentamycin treated or in the sisomicin treated group. Similar results were obtained in incubation tests on both patients and healthy subjects. In conclusion, we conclude that the use of these mentioned aminoglycoside antibiotics, at the therapeutical doses employed, does not interfere with the PMN functions.

Adult↗
PubMed1980

Audiotoxicosis in newborn guinea pigs from pregnant ones given sisomicin.

The audiotoxic effect of sisomicin was investigated in guinea pig injected intramuscularly with 6.25, 12.5, 25 and 50 mg/kg of sisomicin sulfate (potential) during weeks 1--5 or 5--9 of pregnancy, and the transplacental effect on their offspring was studied. While, in some dams the higher doses of sisomicin produced a limited effect on the pinna reflex and the outer hair cells of the organ of Corti, no such effects were noted in any of the offspring during the 3-week postnatal observation period.

Animals↗
PubMed1975

[Pharmacokinetics and clinical observations of sisomicin, a newly developed aminoglycoside derivative (author's transl)].

In a randomized study of 12 healthy subjects the pharmacokinetics of gentamicin, sisomicin and tobramycin were determined after a one-hour infusion of each drug (1.0 mg/kg body-weight) four weeks apart. There were no pharmacokinetic differences of therapeutic significance between the three drugs. The mean serum concentrations at the end of infusion were 3.85 mug/ml for gentamicin and 4.66 mug/ml for sisomicin, falling to 0.12 and 0.26 mug/ml, respectively, after eight hours. The biological half-life varied between 96 and 122 min and the apparent volumes of distribution corresponded closely tothe size of the extracellular space. The antibacterial effectiveness, tolerance and modes of application were studied in 24 patients, most of them with urinary infection, at a dosage of 1.0 mg per kg body-weight two to three times daily. Good clinical results were achieved in 15, satisfactory ones in three, and in 16 the causative bacteria were eradicated. Sisomicin was well tolerated, except for minor and reversible renal (2 patients), hepatic (3 patients), and hearing (1 patient) disturbances.

Adult↗
PubMed1976

Comparison of activity of sisomicin and gentamicin in mouse protection tests with gram-negative bacilli.

The efficacy of sisomicin and gentamicin was compared in mouse protection studies against strains of Escherichia coli, Klebsiella sp., Enterobacter aerogenes, Serratia marcescens, Proteus mirabilis, and Pseudomonas aeruginosa. There was no significant difference in mortality of the mice in any of the protocol groups when five different dosages of sisomicin and gentamicin given by three separate schedules were compared for each bacterial inoculum in each antibiotic protocol. The mean protective dose values of sisomicin were at least one-half those of gentamicin for each protocol against Pseudomonas aeruginosa.

Animals↗
PubMed1976

Sisomicin versus netilmicin: in vitro susceptibility testing.

Antimicrobial susceptibility to sisomicin and netilmicin (Sch 20569) was determined on 164 clinical isolates using a broth microdilution method. Sisomicin was active against 86.1%, and netilmicin against 96.4%, of the isolates. In addition, netilmicin was active against 93.7% of the strains that were resistant to gentamicin, kanamycin, tobramycin, and sisomicin.

Aminoglycosides↗
PubMed1975

[Comparative clinical pharmacology of gentamicin, sisomicin, and tobramycin].

Using a randomized crossover design involving 12 normal subjects, we studied comparatively the pharmacokinetics and tolerance of three aminoglycoside antibiotics, gentamicin, sisomicin, and tobramycin. Serum concentrations were determined during 8 h and the urine recovery rate was determined within 24 h after a 1-h intravenous infusion of the respective antibiotic in a dose of 1 mg/kg of body weight. Microbiological assay was performed with the agar diffusion test (Bacillus subtilis); pharmacokinetic calculations were performed by means of a digital computer on the basis of a mathematical model of an open, two-compartment system. Of the three antibiotics studied, gentamicin showed the lowest concentration in serum after termination of the 1-h infusion (3.85 +/- 0.67 mug/ml), and the serum-regression curve steadily lay below those of the two other antibiotics. Sisomicin had the highest serum concentrations (4,66 +/- 1.24 mug/ml) and the serum-level curve exceeded that of the two other antibiotics. Tobramycin occupied a position between sisomicin and gentamicin in form of its serum level characteristics. Corresponding to the serum kinetics we also found slight differences in the pharmacokinetic parameters, especially in serum half-lives, elimination constants, and areas under the serum level curves. The test of liver and kidney functions and the hematological systems, as well as the function of the stato-acusticus nerve, showed no pathological changes by any of the three antibiotics tested.

Adult↗
PubMed1978

In vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against Pseudomonas aeruginosa.

The in vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against 35 strains of Pseudomonas aeruginosa was investigated. Ticarcillin was more active than carbenicillin and sisomicin was more active than netilmicin. There was enhanced killing of many strains of P. aeruginosa by the combination of carbenicillin or ticarcillin with sisomicin or netilmicin.

Carbenicillin↗
PubMed1978

Uptake of (methyl-14C)-sisomicin and (methyl-14C)-gentamicin into bacterial cells.

Eight sensitive strains (two Staphylococcus aureus, two Escherichia coli, two Pseudomonas aeruginosa and two Klebsiella pneumoniae) and four resistant Pseudomonas aeruginosa strains were used to study uptake of sisomicin and gentamicin by the bacterial cells. In eleven out of the twelve organisms studied employing (methyl-14C)-sisomicin and (methyl-14C)-gentamicin, uptake of the former was found higher that that of the latter. In one organism, the uptake of the two antibiotics was similar. This higher uptake of sisomicin may help explain the superior potency of the antibiotic in relation to gentamicin.

Bacteria↗
PubMed1976

[Binding of sisomicin and gentamicin to serum proteins (author's transl)].

The binding of sisomicin and gentamicin to the proteins of human serum was investigated by the dialysis method at 37 degrees C. The antibiotic concentrations were determined by the disc diffusion assay as well as by measurements of the optical rotation of the antibiotics in the buffer solutions. Serum was dialyzed against buffer solutions to obtain the standards for the antibiotic assay with regard to the electrolytical exchange at dialysis. In studies on protein binding of sisomicin and gentamicin no measurable binding to human serum proteins could be found, neither in the therapeutically possible concentrations nor at higher ones. Therefore a different binding of the two antibiotics cannot be the reason of the advantage of sisomicin over gentamicin in tests in vivo with animals described in literature nor of its higher activity against several bacterial strains of different species tested in the presence of serum.

Anti-Bacterial Agents↗
PubMed1998

[Determination of sisomicin in body fluid by high performance liquid chromatography-indirect photometric detection method].

A high performance liquid chromatography-indirect photometric detection (HPLC-IPD) method for determination of sisomicin sulfate in body fluid (serum, urine, saliva, cerebrospinal fluid and fluid oozed out from wound) was established. The conditions in this method were a mobile phase solution of methyl alcohol-acetonitrile-water (20:10:70) containing nicotinamide 0.5 mmol/L, sodium 1-heptanesulfonate 5 mmol/L and phosphoric acid 0.05 mol/L, a Spherisorb C18 column (4.6 mm x 250 mm) and an UV detector with sensitivity of 0.05 Aufs (0.1 Aufs for urine). The detection wavelength was fixed at 268 nm. The average recovery for sisomicin in serum was 96.92% +/- 4.63% and the coefficients of variation were 4.75% and 5.65% for within-day and day-to-day tests respectively. The detectable limit was 0.1 ng. The concentration of sisomicin in body fluid of 4 patients was determined.

Anti-Bacterial Agents↗
PubMed1991

Central auditory toxicity of sisomicin in guineapigs.

The central auditory toxicity of sisomicin was studied in guineapigs administered sisomicin (135 mg/kg body weight) sc for 10 days. Total lipids, phospholipids and cholesterol were estimated in the pons, inferior colliculus, medial geniculate body and auditory cortex. While the total lipids were increased in a non-preferential manner in all the regions studied, phospholipids and cholesterol levels registered no change. This study suggests the possible central auditory toxicity following sisomicin administration.

Animals↗