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PubMed1988

Ocular penetration of subconjunctivally injected gentamicin, sisomicin and cephaloridine.

The intraocular penetration of three current bactericidal broad-spectrum antibiotics, namely, gentamicin sulphate, sisomicin sulphate (Ensamycin) and cephaloridine, following subconjunctival injection was studied in 95 patients undergoing elective cataract surgery. Rapid and high penetration of all three drugs was evidenced by the fact that the first samples assayed by modified disc diffusion technique 15 minutes after injection showed drug levels effective against all susceptible pathogens. Peak levels of gentamicin, sisomicin and cephaloridine attained one hour after injection were 14.913 +/- 0.310, 19.000 +/- 0.408 and 30.830 +/- 1.195 micrograms/ml, respectively. Such high drug titres would provide drug concentrations 6 to 8 times the minimum inhibitory concentration necessary against susceptible organisms. The duration of the effective bioavailability of the drugs studied varied from 12 to 18 hours. We believe our study is the first to document the excellent penetration of sisomicin and the little-studied drug cephaloridine, and hope our results will open an avenue for in vivo studies to evaluate their clinical use.

Aged↗
PubMed1979

Sisomicin in surgical infections. Laboratory and clinical studies.

A clinical and bacteriological study to evaluate the effectiveness and toxicity of sisomicin in the treatment of surgical infections is described. Fifteen patients received i.m. injections of 150 or 225 mg/day for seven days. The daily doses was divided into three applications. The mean serum levels at the first hour were 5.26 +/- 2.41 microgram/ml and at the seventh hour 1.0 +/- 1.19 microgram/ml. Similar values were determined on the seventh day of treatment with sisomicin: 6.36 +/- 2.36 microgram/ml one hour, 1.17 +/- 1.67 microgram/ml seven hours after i.m. injection. All the microorganisms isolated had MICs below the sisomicin levels measured. The clinical results were assessed as "excellent" in 11 patients. Therapeutic results were considered as "fair" in three patients. The clinical conditions of one patient affected by osteomyelitis following osteosynthesis of the femur was not improved by treatment. No side effects were observed.

Adolescent↗
PubMed1985

[Pharmacokinetics of sisomicin during hemosorption and hemodialysis].

The effect of hemosorption and hemodialysis on the pharmacokinetics of sisomicin was studied in 17 patients with acute and chronic renal insufficiency. The value of the antibiotic extraction coefficient in hemosorption was almost 2 times higher than that in hemodialysis. In patients on hemosorption, extracorporeal elimination of the antibiotic was of the saturation nature. It was characterized by systematic diminishing of the extraction coefficient, while in patients on hemodialysis, it did not depend on the time (the value of the extraction coefficient was constant). In this connection it is recommended that the rate of diminishing of the extraction coefficient in hemosorption be estimated. Since sisomicin is rapidly absorbed by the column it is not advisable to administer sisomicin to patients before hemosorption.

Acute Kidney Injury↗
PubMed1985

[Effectiveness of the new aminoglycoside sisomicin in surgery].

Antimicrobial activity of sisomicin against causative agents of wound infections was studied. It was shown that by its antimicrobial activity and the rate of bactericidal effect attainment sisomicin is superior to other aminoglycosides, such as gentamicin and tobramycin. Individual variability of the pharmacokinetics of sisomicin on its intravenous and intramuscular injection to patients with wound infections was observed. For prediction of the treatment efficacy it is suggested that the drug be used under the control of its blood levels in comparison to the MTC for the isolated causative agent.

Drug Evaluation↗
PubMed1983

[Effect of sisomicin i on elements of the peripheral nervous system].

In long-term experiments with anesthetized cats and albino mice sisomicin and gentamicin were found to impair the impulse conduction in the skeletal muscle synapses and in the ganglia of the sympathetic and parasympathetic nervous systems. Comparison of the drug doses inducing the above effects in experimental animals showed that the neuroblocking activity of sisomicin was almost 3 times higher than that of gentamicin. Since the therapeutic doses of sisomicin used in the treatment of patients are 2.5-3 times lower than the respective doses of gentamicin, it must be considered that both the drugs had the same ranges of the therapeutic activity from the standpoint of their side effects.

Animals↗
PubMed1984

In vitro evaluation of ceftazidime (GR 20263), amikacin and sisomicin, in a model simulating serum pharmacokinetics of therapeutic doses.

The activity of ceftazidime, amikacin and sisomicin was investigated in an in vitro model using varying concentrations of antibiotic which mimic the serum levels of patients after the intramuscular administration of a 500, 250 and 70 mg dose respectively. Using this test, during the time of the agar MIC value correlation, ceftazidime, amikacin and sisomicin proved to be active against strains sensitive to 16 micrograms/ml, 8 micrograms/ml and 4 micrograms/ml respectively. Using the above concentrations as the cut-off points in defining the sensitivity of the strains, ceftazidime revealed the same level of activity as amikacin (6 and 5 resistant strains respectively out of the 185 tested) and proved much more active than sisomicin (48 resistant strains).

Amikacin↗
PubMed1981

Evaluation of therapeutic efficacy of ureidopenicillins in comparison to sisomicin and cephalotin in experimental infections of rabbits.

The therapeutic efficacy of azlocillin, mezlocillin, cephalotin, and sisomicin was evaluated by experimental infection in rabbits. After one hour following infection with Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa, antibiotics were applied intramuscularly. Colony-forming units were counted before the infection and every day thereafter. Leukocytosis was determined before infection and 3 and 7 days after initiation of therapy. Therapy with antibiotics was continued for seven days, rabbits sacrificed and CFU/g tissue determined. It was shown that in experimental infection caused by E. coli or K. pneumoniae in rabbits, sisomicin was most effective, followed by mezlocillin, azlocillin, and cephalotin. Efficacy of therapy against P. aeruginosa was as follows: sisomicin, azlocillin, mezlocillin.

Animals↗
PubMed1982

[Comparative study of the effect of sisomicin and other aminoglycosides on the causative agents of surgical infection].

Sensitivity of sisomicin was studied with respect to the causative agents of surgical infections. The microbial species belonging to the following genera were tested: Staphylococcus, Klebsiella, Escherichia, Proteus and Pseudomonas. The comparative studies with amykacin, tobramycin and other aminoglycoside antibiotics showed that sisomicin had the highest activity against Staphylococci, Klebsiella, Proteus and Ps. aeruginosa. Its activity against E. coli was equal to that of gentamicin and tobramycin. The percentage of the strains resistant to sisomicin was lower than that of the strains resistant to the other aminoglycoside antibiotics except amykacin.

Aminoglycosides↗
PubMed1980

Experimental infection in rabbits evoked by Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli and Klebsiella pneumoniae treated with gentamicin, amikacin and sisomicin.

Rabbits were infected with freshly isolated strains of Ps. aeruginosa, P. mirabilis, E. coli or K. pneumoniae and treated with gentamicin, amikacin or sisomicin in a controlled study. Therapeutic results were evaluated by survival of animals and viable counts of etiologic bacteria in several tissues after sacrification of treated animals at the same time. Sisomicin was the drug of choice for Ps. aeruginosa and P. mirabilis infections, when compared with amikacin and gentamicin. Its action is practically equal to that of amikacin in K. pneumoniae infection. Sisomicin appeared less active in E. coli infections than amikacin, but was superior to gentamicin.

Amikacin↗
PubMed1978

[Experimental investigations concerning a topical application of sisomicin in the eye (author's transl)].

Sisomicin is a new aminoglycoside, which sometimes is active against bacterial isolates resistant to other antibiotics of this group. The compatibility of sisomicin and its penetration into the different tissues of the eye were studied in rabbits. The substance was well tolerated, when applied as drops or injected subconjunctivally. Concentrations of sisomicin which are effective against most bacteria were found in the cornea and in the aqueous humour, but it did not penetrate into the vitreous body.

Animals↗
PubMed1976

[Antibacterial activity of sisomicin in comparison with gentamicin].

The antibacterial activity of sisomicin -- a new aminoglycoside antibiotic -- as compared with gentamicin was tested on 521 bacterial strains of different species in a serial-dilution test. Staphylococci, streptococci, E. coli, Klebsialla-Enterobacter, indole-psitive Proteus strains, pseufomonads, Salmonads, Salmonellae, and Serratia marcescens were inhibited to the extent of 100% at a maximun of 4.0 mug/ml. Sisomicin showed a higher antibacterial activity against part of the bacterial species. Gentamicin-resistant pseudomonads and Klebsiella (clinical isolates) were still inhibited to the extent of 42 and 67%, respectively, by sisomicin. In addition to the determination of the MIC values for the use of different liquid media, investigations on the determin ation of the minimal bactericidal concentration (MBC), the effect of serum, pH, and inoculum on the bacterial activity, and investigations on the resistance development in vitro were also carried out.

Anti-Bacterial Agents↗
PubMed1978

In vitro comparison of kanamycin, kanendomycin, gentamicin, amikacin, sisomicin, and dibekacin against 200 strains of Pseudomonas aeruginosa.

The antimicrobial activity of kanamycin, kanendomycin, gentamicin, amikacin, sisomicin, and dibekacin against 200 strains of Pseudomonas aeruginosa was compared. Dibekacin was found to be the most active against the tested organisms, whereas the other aminoglycoside antibiotics fell in the following order of diminishing antibacterial potency: amikacin, sisomicin, gentamicin, kanendomycin, and kanamycin. Seven strains showed high-level resistance to gentamicin (minimal inhibitory concentration, 400 mug/ml), and two of them were also resistant to amikacin and sisomicin (minimal inhibitory concentration, 75 mug/ml). The minimal inhibitory concentration of dibekacin for these seven strains was 0.625 mug/ml.

Dibekacin↗
PubMed1975

Sisomicin: Bacteriological and clinical evaluation.

A preliminary study was conducted with sisomicin, a new aminoglycoside antibiotic. The drug was administered to 40 patients in doses varying from 1.5 to 3.75 mg/kg/day. Sisomicin proved to be an effective therapy in urinary tract infections and to a lesser extent in wound infections caused by gram-negative rods; favorable results have been observed in 91.6% and in 66.6% of the patients presenting these infections. Toxic reactions involving the hearing function, renal function, and general tolerance were infrequent: they occurred in less than 5% of the patients in this series. (However in approximately 22% of the patients, there was a transient appearance of granular casts in the urine.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparative trial of single-dose versus twice-daily sisomicin in bacteriuric patients.

Sisomicin was administered as a single daily intramuscular injection (160 mg) or as two daily injections (80 mg) to 50 patients with bacteriuria superimposed on chronic urologic diseases in a randomized controlled fashion. The administration of two daily doses was significantly more effective (P less than 0.01) in achieving cure than the injection of a single daily dose. The renal function, as expressed by creatinine clearance, became impaired significantly more often (P less than 0.05) in the patients receiving the single daily dose of sisomicin.

Adult↗
PubMed1982

[Studies with azlocillin, mezlocillin, penicillin-g-potassium and sisomicin on tolerance in the cornea and the kinetics of inhibiting concentrations in the cornea and aqueous humor in rabbits].

We studied the effect of azlocillin, mezlocillin and sisomicin in concentrations of 1, 2.5 and 5% on the regeneration of stromal corneal wounds in rabbits following subconjunctival injections and treatment with eye drops. Concentrations of the antibiotics were also determined in corneal tissue and in aqueous humor and compared with that of penicillin G-potassium. Together with azlocillin, sisomicin proved to be the most effective and the safest. Mezlocillin only inhibited wound regeneration slightly and thus mezlocillin appears to be inferior to the other two antibiotics investigated in the local treatment of the eye.

Animals↗
PubMed1978

[Efficacy, tolerance, and pharmacokinetics of sisomicin in urinary tract infections (author's transl)].

Since 1973 30 patients with urinary tract infections (UTI) or pyelonephritis have been treated with sisomicin, a new aminoglycoside, in a daily dose of 2 mg/kg for a period of seven to nine days. From a clinical point of view the result of treatment was good. Complete resolution was achieved in 17 patients, improvement in nine, and there was no effect in four patients. Thirty-five causative organisms (Escherichia coli = 23, Proteus sp. = 7, Klebsiella sp. = 3, Pseudomonas aeruginosa = 1, Citrobacter = 1) were isolated before treatment. Thirty of the organisms were eliminated during treatment, but seven reappeared during the follow-up period; five strains persisted. Side effects observed consisted of reversible increase of serum creatinine in four patients, excretion of granular casts in 14 patients, and a transient rise of alkaline phosphatase, SGOT and/or SGPT in five patients. No signs of ototoxicity or any other adverse reactions were found and local tolerance was good. In 20 patients blood samples for assay were obtained daily one hour after i. m. injection of 1.0 mg/kg. No evidence of drug accumulation in the serum was found: the mean serum concentrations one hour after injection remained between 3.4 and 3,9 microgram/ml during the entire treatment period. Sisomicin is a highly effective antibiotic for the treatment of UTI caused by gramnegative pathogens. On account of its potential toxicity however, it should be used, like other aminoglycosides, only in selected cases.

Anti-Infective Agents, Urinary↗
PubMed1983

The combined action of azlocillin and sisomicin in a model simulating the in vivo serum kinetics.

The in vivo serum kinetics of azlocillin and sisomicin were simulated in a new in vitro test model. A strong synergistic effect against Pseudomonas aeruginosa resulted when both compounds were administered simultaneously and eliminated according to their individual half-life values, even when the decreasing drug concentrations exceeded the MICs for only a short period of time. When applied at intervals, neither pretreatment with azlocillin nor with sisomicin blocked the antibacterial activity of the combination partner.

Azlocillin↗
PubMed1984

Determination of sisomicin, netilmicin, astromicin and micronomicin in serum by high-performance liquid chromatography.

A high-performance liquid chromatographic method for monitoring serum levels of the aminoglycoside antibiotics sisomicin, netilmicin, astromicin, and micronomicin, using an amino acid analysis system is described. The procedure involves sample preparation with a CM-Sephadex column, and quantitation using internal standards chosen from each of the other aminoglycosides. The aminoglycosides were separated by reversed-phase ion-pair chromatography on Zorbax C8 and ODS columns, and detected by the post-column derivatization technique. The calibration curves of serum concentration for sisomicin, netilmicin, astromicin, and micronomicin were linear over the ranges 0.32-22.8 micrograms/ml, 0.17-11.6 micrograms/ml, 0.1-6.3 micrograms/ml, and 1.0-30 micrograms/ml, respectively. The coefficients of variation were 2.5, 2.8, 3.1 and 1.9%, at the serum concentrations of 1.3, 1.45, 1.58 and 2.5 micrograms/ml, respectively (n = 6). Determination by the internal standard method using another aminoglycoside gives accurate and reproducible results. This method is applicable also to other aminoglycoside antibiotics.

Aminoglycosides↗