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[Morphological changes in the retina following one-shot injection of netilmicin sulfate into the vitreous].

Morphological changes of the retina following one-shot injections into the vitreous of netilmicin sulfate were investigated. The concentrations of netilmicin in the vitreous after intravitreal injection showed the curve of y = a/xb, where y is the concentrations in the vitreous body, x in the number of days since injection and a, b are constant. Concentration decreased rapidly after the injection, and almost totally disappeared after one week. Morphologically, the retina showed normal structure following injections of 100 micrograms/0.1ml and 200 micrograms/0.1ml. Following injections of over 500 micrograms/0.1ml, the outer segment of the photoreceptor disappeared and many phagosomes appeared in the retinal pigment epithelium cell. Following one shot injections of over 500 micrograms/0.1ml damage to the photoreceptor and retinal pigment epithelium was demonstrated. The above data suggested that one-shot injection of netilmicin in concentrations of up to 200 micrograms/0.1ml could be mode without retinal damage.

Animals↗

[Netilmicin in the treatment of bacterial respiratory tract infections].

Netilmicin - a semisynthetic aminoglycoside - was administered to 33 patients with the acute or chronic lower respiratory tract or pulmonary infections in a daily dose of 5 mg/kg body weight for 10 days. A principle criterium of patients classification to netilmicin therapy were sensitive bacterial strains either in sputum or in BAL liquid. A significant clinical improvement was noted in 88% of the treated patients. However, elimination of pathogens from the sputum was achieved only in 52% of these patients. No improvement was observed in 4% of the treated patients. No adverse reactions were noted. Netilmicin proved safe and effective antibacterial agent in patients with respiratory infections.

Adult↗

[Netilmicin in a single daily dose for treatment of systemic infections].

The Authors report the results obtained in 35 patients of either sex suffering from various systemic infections and treated with netilmicin. Netilmicin has been intramuscularly administered in once daily dose of 4.5 mg/kg (mean daily dose 294.3 mg) for a mean duration of 17.8 days. The clinical resolution of the infections has been achieved in 97.1% (34 patients) of the study population; only one patient showed failure. Thirty-three of the 35 baseline causative pathogens have been eradicated. The local and systemic tolerability was good. The serum pharmacokinetics showed bactericidal levels of netilmicin and no serum accumulation.

Adult↗

[Single dose administration of netilmicin in the treatment of urinary tract infections].

The authors submit the results of treatment of non-complicated urinary tract infections by a single dose of netilmicin. They treated 23 patients to whom they administered a single dose of 200 mg netilmicin by the i.m. route. A positive short-term effect was recorded in 82.8%. Cases of failure of this treatment indicate the necessity of careful indication of a single dose of netilmicin only to patients with non-complicated infections of the urinary pathways.

Adult↗

Residual bodies in the retinal pigment epithelium induced by intravitreal netilmicin.

Intravitreal injection of aminoglycoside antibiotics is known to induce morphological changes in the retinal pigment epithelium (RPE) resembling a lipidosis. The RPE of netilmicin-treated rabbits displays a dose-related increase in autofluorescence compared to untreated controls. Netilmicin produces an accumulation of membrane-limited osmiophilic lamellated inclusions in the pigment epithelial cell. These inclusions measure from 1 to 3 microns in diameter, and have acid hydrolase activity demonstrated by cytidine monophosphate cytochemistry. These findings suggest that netilmicin-induced inclusions are residual bodies and that the accumulation of these residual bodies is responsible for the observed cellular lipidosis.

Animals↗

[Pharmacokinetics of netilmicin in cirrhotic patients with or without ascites].

The pharmacokinetics of netilmicin after intramuscular injection (2 mg/kg) was investigated comparatively in cirrhotic patients with or without ascites, and in healthy subjects. In patients with ascites, the same pharmacokinetic parameters were measured after the ascites had been cured. Twenty-four hours after intramuscular injection, the residual levels in cirrhotic patients were moderately higher than in controls, showing that liver failure or ascites did not significantly modify the pharmacokinetics of netilmicin. Serum concentrations were bactericidal. The ascitic fluid level was lower than the therapeutic range, but it was sustained for nearly 24 hours after intraperitoneal injection (2 mg/kg). These results indicate that netilmicin may be administered to cirrhotic patients without peritoneal infection using the same regimen as in healthy subjects. The peritoneal route may be preferable in case of peritoneal infection.

Adult↗

Pharmacokinetics of netilmicin in renal insufficiency and hemodialysis.

The pharmacokinetics of netilmicin was studied in 26 patients with varying degrees of renal impairment (11 were dialysis patients) in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum level curves of netilmicin follows a two-compartment open kinetic model. Several relationships between pharmacokinetic parameters and renal function indicators are defined. A clinical useful correlation indicates that the half-life is approximately 3 times the serum creatinine concentration, and may be used for adjusting the netilmicin dosage in the treatment of patients with impaired renal function. During hemodialysis the serum half-life decreases approximately 10-fold compared with the interdialysis periods. The percentage of dose extracted by hemodialysis during a single 4 h session is 56.1 +/- 6.65%. The dialysis clearance is 87.28 +/- 28.8 ml/min.

Adult↗

[Habekacin: a new aminoglycoside. Study of nephrotoxicity in rats in comparison with gentamicin, netilmicin and amikacin].

Habekacin is a new aminoglycoside antibiotic. In this study we want to know the effect of increasing dose of habekacin on renal function and on renal morphology. We decide to compare the renal alterations induced by habekacin to these provoked by gentamicin, netilmicin and amikacin. Female Wistar rats received intraperitonally a single injection daily of 10, 30, 50, 150 mg/kg of habekacin for seven days. Wistar rats received also 50 mg/kg gentamicin, 50 mg/kg netilmicin and 150 mg/kg amikacin. No mortality was observed in groups treated with 10, 30, 50 mg/kg habekacin but 50 per cent of rats died with 150 mg/kg habekacin. Habekacin--30 mg/kg seven days--induced a decrease of cortical enzymatic activities, an increase of the number of lysosomes, a great accumulation of myeloid bodies, an alteration of lysosomal membranes Habekacin--50 mg/kg seven days and 150 mg/kg--induced a decrease of creatinine clearance and ultrastructural alterations of renal tubular cells. Comparative studies with other aminoglycosides showed that amikacin--150 mg/kg was the lesser nephrotoxic drug. With a same dose of 50 mg/kg, gentamicin appeared lesser nephrotoxic than habekacin and habekacin seemed to induce a same degree of renal modifications than netilmicin. With the dose of 150 mg/kg habekacin this drug was higher nephrotoxic than 50 mg/kg gentamicin. In conclusion, if it could be necessary to use habekacin and to prefer this aminoglycoside to gentamicin from an antibacterial activity point of view it is necessary to keep in mind that this drug is potentially nephrotoxic and that the dosage had to be strictly respected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗

[In vitro effect of combinations of netilmicin and amikacin with fosfomycin and pefloxacin on 31 strains of heterogeneous methicillin- resistant Staphylococcus aureus].

The Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) of 31 strains of Staphylococcus aureus resistant to methicillin and gentamicin were determined towards aminoglycosides: netilmicin (N) and amikacin (A). The results of the study showed a large discordance between the technic using dilution in Mueller-Hinton broth and the technic using agar diffusion with antibiotic discs. The level of sensitivity appears to decrease by dilution. The problem of using these aminoglycosides in combination with other antibiotics as fosfomycin (F) and pefloxacin (P) was faced. In vitro, antibacterial activity of combinations [N-F], [N-P] and [A-F], [A-P], was studied by microtiter checkerboard method. The antibacterial effects of these combinations were evaluated by determination of Fractional Bactericidal Indices (FBC-indices). The combination netilmicin or amikacin with pefloxacin has an additive bactericidal effect in most cases, without discrimination between the different aminoglycosides (FBC #0.82). Netilmicin or amikacin in combination with fosfomycin are found to be additive or moderately synergistic (FBC #0.53). No occurrence of antagonism was observed.

Amikacin↗

The treatment of gynaecological and intra-abdominal infections: a comparative study of cefotetan versus netilmicin plus clindamycin.

In a prospective randomised study 60 patients with gynaecological or intra-abdominal infections were given either 2g iv every 12 hours of cefotetan or a combination of netilmicin (150mg iv every 12 hours) and clindamycin (600mg iv every 8 hours). The clinical condition of nearly half the patients (26 of 60) was characterized as serious and surgical manipulation and drainage were performed in 57 of the 60 patients. The clinical response was similar in both groups with 21 of 29 patients in the cefotetan group and 29 of 33 patients in the netilmicin plus clindamycin group. Side effects were few and mild in nature with no significant differences between the two groups. This work is continuing but the results to date suggest that cefotetan monotherapy is a safe and effective alternative to a combination of netilmicin and clindamycin in the treatment of gynaecological and intra-abdominal infections.

Abdomen↗

[The effect of netilmicin on gram negative rods isolated in the Konya region].

Netilmicin, was tested for the effect against 276 isolates of gram negative bacteria, before had used in Konya region. 15.9% of the isolates were resistant and 84.1% were sensitive to netilmicin. The effects of Netilmicin and gentamicin for 50 Pseudomonas isolates were compared. The other aminoglycosides also were tested against isolates of the bacterium, amikacin was the most active one.

Enterobacteriaceae↗

Pharmacokinetics of ceftazidime and netilmicin in patients with sepsis.

The pharmacokinetics of ceftazidime and netilmicin were evaluated under septicemic conditions. In a longitudinal study, both drugs were administered simultaneously (ceftazidime 2.0 g 20 min constant i.v. infusion and netilmicin 150 mg i.v. bolus injection) every 12 hours to patients who had a positive blood culture and hyperdynamic circulatory functions. Twenty-four hours after the first period of this pharmacokinetic study, identical parameters were evaluated under dipyrone induced normothermic conditions. The mean residence time and the volume of distribution was significantly altered during septicemia compared to normal conditions. With respect to the relative distribution properties ceftazidime tended to be distributed to a greater extent to the tissue compartment, whereas netilmicin showed an opposite behaviour. Beside significant correlations of absolute values, i.e. blood volume vs. volume of distribution, and relative values, i.e. total peripheral resistance vs. extraction rate, all other attempts failed to show any meaningful correlation. Owing to the heterogenous alterations of metabolic and hemodynamic functions and pharmacokinetic parameters, respectively, the data gained from this study do not allow any statistically validated conclusion regarding the pathophysiological mechanisms involved, although these findings are in accordance with animal experiments.

Adolescent↗

Comparison of netilmicin with ceftriaxone for the treatment of severe or complicated urinary tract infections.

A randomised trial was undertaken to compare the efficacy of netilmicin and ceftriaxone for the treatment of severe or complicated urinary tract infections. Forty-seven patients completed the study. Twenty-three of 24 patients treated with netilmicin and 21 of 23 treated with ceftriaxone were cured. One patient treated with netilmicin had a mild, reversible disturbance of renal function. Six patients developed diarrhoea after ceftriaxone treatment.

Adolescent↗

[Serum and bronchial concentrations of netilmicin during its continuous intratracheal administration].

Respiratory tract infections in intensive care units have a high fatality rate, perhaps as a result of the poor diffusion into bronchial secretions of aminoglucosides given by a systemic route. Endotracheal administration of aminoglycosides has been advocated but the optimal dosage remains to be determined. To investigate this problem we studied 13 patients free of renal failure and 6 patients with renal failure. Netilmicin was given by continuous endotracheal infusion in a daily dosage of 3 to 30 mg/kg. A good correlation was found between infused doses and serum concentrations; very high bronchial secretion concentrations were consistently found. There is a significant risk of accumulation in patients with renal failure. The characteristics of the respiratory tract secretions had no influence on the passage of netilmicin into the bloodstream. The dosages we advocate on the basis of our results are 8 mg/kg/day in patients free of renal failure and 4 mg/kg/day in patients with renal failure; serum netilmicin concentrations should not exceed 1 microgram/ml.

Adult↗

A comparison between netilmicin with metronidazole and doxycycline as prophylaxis in elective colorectal surgery.

The aim of this study was to compare the prophylactic effects of netilmicin plus metronidazole administered for one day and of doxycycline administered for five days on the incidence of postoperative sepsis in patients undergoing elective colorectal surgery. One hundred patients were studied, 50 men and 50 women, with a mean age of 66.6 years. The patients were randomized into the two groups. Wound infections occurred in a total of 9 patients, 5 in the doxycycline group and 4 in the group given netilmicin plus metronidazole, i.e. the overall infection rate was 9%. It is concluded that there is no statistically significant difference on the incidence of postoperative wound sepsis in patients undergoing elective colorectal surgery between the group given doxycycline for five days and the group given netilmicin plus metronidazole for one day.

Adolescent↗

Changes in resistance to aminoglycoside antibiotics of different bacterial strains isolated during the period 1978 to 1983. Netilmicin as alternative therapy.

The percentage resistance of 11,404 gram-negative and gram-positive bacterial strains isolated from different biological materials between 1978 and 1983 to some aminoglycoside antibiotics (gentamicin, tobramycin and amikacin) was determined. The percentage of resistant Pseudomonas, Staphylococcus and indole-positive Proteus organisms significantly increased. There was also a significant decrease in gentamicin-resistant strains of the Escherichia coli and Proteus mirabilis species. We also compared the in vitro activity of netilmicin (routinely tested from the beginning of 1983) with those of the other aminoglycosides against 1546 bacterial strains. Netilmicin was found to have greater antibacterial activity than gentamicin or tobramycin. In addition, netilmicin was active against 48.9% of the strains that were resistant to gentamicin and/or tobramycin.

Amikacin↗

Netilmicin in the treatment of infections in patients with cancer.

Ninety-two patients with cancer with 100 infectious episodes were treated with netilmicin sulfate, a new aminoglycoside. Netilmicin was administered intravenously, either intermittently or by continuous infusion. The overall cure rate was 60%. Gram-negative bacilli were the most common causative organisms and the response rate for these infections was 32/53 (60%). The most common pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia, urinary tract infection, and septicemia were the most common types of infection treated and the response rates were 23/47 (49%), 19/21 (90%), and 9/17 (53%), respectively. Nephrotoxicity occurred in ten patients (6%) who had normal renal function initially. Netilmicin is an effective aminoglycoside with a spectrum of antibacterial activity similar to that of gentamicin sulfate and it appears to be less nephrotoxic.

Bacterial Infections↗

[Use of netilmicin for antibiotic prevention of urinary infections after endoscopic surgery in urology].

We studied for one year 60 patients separated in 3 groups of 20: first reference group without treatment; second group receiving netilmicin in premedication; third group treated by netilmicin for 2 days postoperatively. This series clearly demonstrates the high urinary tract infection rate after transurethral surgery, the benefit of antibioprophylaxis with netilmicin and the efficiency of one dose of this aminosid given one hour preoperatively.

Aged↗