The following are results obtained with in vitro antibacterial activity of Netilmicin, compared with other aminoglycoside antibiotics.
Netilmicin showed a broad spectrum of activity with a potent bactericidal action nearly identical to that of Gentamicin. In susceptibility testing of clinical isolates, Netilmicin inhibited all strains of E. coli, K.pneumoniae, indole-negative Proteus, S. aureus, and C. freundii, about 95% of P. aeruginosa, indole-positive Proteus, and E. cloacae, and about 80% of S. marcescens at a concentration of 6.3μg/ml or less.
Many Gentamicin-resistant strains of S. marcescens, E. coli, and Proteus were sensitive to Netilmicin, while there was a tendency of cross-resistance between the drug and Gentamicin in P. aeruginosa.
As with Gentamicin, the activity of Netilmicin was weaker at acidic pH, and was not much influenced by inoculum size or addition of serum to the medium.

View full abstract

The antibacterial activity of netilmicin against 612 strains of pathogens isolated from clinical materials at the Clinical Laboratories of Juntendo University during 1978 to 1979 was assessed. S. aureus, S. epidermidis, E. coil, Klebsiella, E. cloacae, Serratia, C. diversus, C. freundii, P. mirabilis, P. vulgaris, P. morganii, P. rettgeri, P. inconstans, P. aeruginosa and A. anitratus were tested. The minimum inhibitory concentration (MIC) of netilmicin was compared with that of gentamicin, tobramycin and amikacin.
Except for strains of C. freundii and P. mirabilis some strains of other isolates were shown to be resistant to netilmicin. MICs of netilmicin were correlated to those of gentamicin in general, however, the gentamicinresistant and netilmicin-sensitive strains were observed in many strains. MICs of netilmicin were not correlated to that of amikacin.

View full abstract

The following were results of in vitro and in vivo studies on Netilmicin, a new aminoglycoside antibiotic, compared with Gentamicin (GM) and Amikacin (AMK).
Netilmicin showed a broad spectrum of antibacterial activity similar to that of GM and was active against some GM-resistant strains of P. aeruginosa, S. marcescens, P. mirabilis, C. freundii, and K. pneumoniae.
Against experimental infections of mice with E. coli, Proteus, Klebsiella, Serratia, and P. aeruginosa, Netilmicin demonstrated therapeutic effects nearly parallel to MICs, showing significantly low ED₅₀ values against the strains that were resistant to GM or AMK but were sensitive to Netilmicin.
The presence of many GM-resistant C. freundii strains that were sensitive to Netilmicin was noteworthy.

View full abstract

Three series of experiments were performed to evaluate the ototoxicity of netilmicin in 80 rats (Sprague-Dawley) and 33 guinea pigs (Hartley). In order to evaluate the auditory impairment in the animals the pinna reflex test was carried out in a wide frequency range from 20KHz to 500Hz before, during and after the administration of netilmicin and gentamicin. Upon completion of the drug administrations histopathological investigations were made on the serial celloidin sections in horizontal direction of the inner ears in the rats and guinea pigs. In addition, supravital reduction reaction with nitrs blue tetrazolium (Nitro-BT) was conducted on the inner ears which were removed immediately after guinea pig decapitation. This was done to evaluate the reduction potency in the electron transport system in the surviving hair cells of the cochlea.
Series 1. a) Comparative evaluation of ototoxicity of netilmicin and gentamicin in rats
Netilmicin andgentamicin were given intramuscularly at various doses of 30, 90 and 120mg/kg, respectively for 3 weeks. Pinna reflex loss was not detected in animals of either group. Histopathologically, at 30mg/kg there were no animals missing the aminoglycoside sensitive outer hair cells of the spiral organ. However, at 90mg/kg the loss of the outer hair cells occurred in 11% of netilmicin treated animals and in 30% of gentamicin treated ones. At 120mg/kg the loss of the outer hair cells was seen in 11% of the netilmicin animals and in 100% of the gentamicin ones. The loss of these outer hair cells was relatively localized in the lower part of the basal turn of the cochlea in the netilmicin animals, but more extensive in the gentamicin treated animals. On the other hand, scattered loss of the hair cells in the vestibular organs including the cristae ampullares of the semicircular canals and the utricular as well as saccular maculae was found in the animals of both groups. There was no remarkable difference in vestibular toxicity between the netilmicin and gentamicin rats.
b) Ototoxicity and nephrotoxicity
According to the comparative nephrotoxicity study of netilmicin and gentamicin in the rats performed by the coworkers, Prof. Yasushi Ueda and Dr. Atsushi Saito (Department of Internal Medicine, The Jikei University School of Medicine, Tokyo), the gentamicin treated rats showed a dose dependent alteration in nephrotoxicity, while the netilmicin treated rats showed little alteration. Our results indicated that the nephrotoxicity tendencies seen with netilmicin and gentamicin were also similar for ototoxicity.
Series 2. Evaluation of ototoxicity of netilmicin in guinea pigs.
Netilmicin was administered intramuscularly at doses of 50mg/kg and 100mg/kg, respectively for 4 weeks. Loss of the pinna reflex did not occur in any animals of both groups. Loss of the outer hair cells in the basal end of the cochlea was found in only one animal treated with netilmicin at 100mg/kg. Decrease in the number of spiral ganglion cells occurred in only the upper part over the fourth turn of the modiolus in one animal from each group without the loss of the outer hair cells in the corresponding spiral organ. In the vestibular organs a scattered loss of hair cells was found in all animals of both groups. The results of the present and previous guinea pig experiments suggest that netilmicin is less ototoxic than amikacin, dibekacin and kanam ycin.
Series 3. Combined administration with netilmicin and furosemide
A single injection of netilmicin (100mg/kg, i. m.) was given to 3 guinea pigs and 2 hours later furosemide (100mg/kg, i. v.) was administered. The pinna reflex test revealed that a transient auditory impairment was induced in a wide frequency range (20 to 0.5KHz) immediately after the furosemide administration. The loss of the pinna reflex lasted for about 30 minites, then decreased in frequency range and localized at 20KHz.

View full abstract

The nephrotoxic potentials of netilmicin and gentamicin were compared in SD strain rats at intramuscular daily doses of 30, 90, and 120mg/kg for 21 days, and 150mg/kg for 7 days, respectively.
In renal function test, gentamicin group tended to produce more abnormal changes than netilmicin group with respect to protein, sugar, and lysozyme excretions in the urine at 30 and 90mg/kg doses, and BUN and serum creatinine at 150mg/kg dose; however, there were no significant differences in urine osmolality between both drugs.
Histopathologically, main lesions were found in the proximal convoluted tubular epithelium in both netilmicin and gentamicin groups. A finding observed with netilmicin group at 30mg/kg dose was very slight degeneration without necrosis, whereas that found with gentamicin group at same dose was partial necrosis. Renal injury caused by gentamicin was enhanced in a dose-related manner, while netilmicin showed a gentler dose-response curve than gentamicin and at 150mg/kg dose, the fundamental structure of the kidneys was retained relatively well.
Histochemically, the decreased activity of alkaline phoshatase reflecting the hypofunction of the active transport in the brush border was more found in gentamicin group than in netilmicin group. The increased activity of acid phosphatase was observed in both groups, which was considered to be indicative of the elevated activity of lysosome in the proximal convoluted tubular epithelium.

View full abstract

Netilmicin, a new semisynthetic aminoglycoside antibiotic, has been investigated to give following results.
The MIC values for Netilmicin against 532 strains of P. aeruginosa, isolated from patients, were measured by the plate dilution method with an inoculum size of 10⁸cells/ml. Eighty percent of all strains were found to be sensitive to Netilmicin at 12.5μg/ml or less.
The MIC values for Gentamicin were lower than those for Netilmicin against these strains.
A pharmacokinetic study of Netilmicin was conducted in 6 healthy male volunteers after single intramuscular 75mg or 100mg administration. The mean peak concentrations in serum following administration of each dose were 5.6μg/ml and 8.2μg/ml at 1/2 hour, respectively. There were significant differences in the AUC and Cmax, and also serum levels at each point. It was found to be dose response between two injected doses. The urinary recovery rates were 71.2% and 73.5% of the dose during 6 hours, respectively. The tolerance following administration of two doses of Netilmicin was good.
Twenty-five patients (3 cases with respiratory tract infections, 1 case with peritonitis, and 21 cases with urinary tract infections) were treated with Netilmicin of 75mg or 100mg b. i. d. Fourteen cases were excellent, nine were good, one was fair and another one was failed. Bacteriological responses were favorable, especially E. coli (13 strains) and Klebsiella (3 strains) isolated from the urine were eliminated. Two patients had mild pain at injection site. No laboratory abnormalities were observed.

View full abstract

1) One patient with acute cystitis and 24 patients with respiratory tract infectious diseases including 15 of acute pneumonia, 6 of bronchitis chronica, each 1 of bronchiectasis, pyothorax and pneumonitis purulenta, were treated with Netilmicin.
There were 15 males and 10 females. 12 of them were aged over 60 years old.
12 of them had some severe basic or complicated diseases such as lung cancer, lung tuberculosis, pneumoconiosis, asthma, hypertension and neurological ischiuria.
2) Organisms, found in sputum or specimens from mouth-secret and urine, were 6 strains of Staphylococcus aureus, 4 strains of Klebsiella, 4 strains of Gram positive cocci, 3 strains of Haemophilus influenzae, 3 strains of Gram negative bacilli, 2 strains of Enterobacter cloacae, 2 strains of Streptococci, each one strain of Pseudomonas, Proteus, Gram positive diplococcus, Gram negative coccus and Neisseria.
3) A dose of Netilmicin was 75-100mg, given twice daily, and it was administered intramuscularly for 4 to 14 days, 600-2, 800mg in total.
4) Clinical effects were as follows: 7 excellent cases and 14 good cases were observed, and the total effectiveness was seen in 84% of the cases.
Usefulness was judged as follows: Very useful in 14 cases, useful in 8 cases and rather useless in 1 case were seen.
5) Side effects: Administration of Netilmicin had to be discontinued in 1 case after 10 days due to the local pain at the injection site.
Increase of alkaline phosphatase and γ-GTP values were found in 1 case after 14 days, and 1 case showed transient albuminuria in the course of the treatment.
From the above results, it may be concluded that Netilmicin is a drug for severe pulmonary and urinary tract infectious diseases.

View full abstract

To evaluate the clinical efficacy of netilmicin, the treatment was conducted with the drug in 3 patients with acute pneumonia, 5 with acute cystitis, 14 with chronic cystitis, 4 with acute pyelitis and 1 with chronic pyelitis. Responses were excellent in 9 patients, good in 14 patients and poor in 4 patients. Bacteriological effects of netilmicin in urinary tract infection by causative organisms were excellent.
Side effects were noticed as GOT and GPT elevations in 1 patient and BUN elevation in 2 patients.

View full abstract

Laboratory and clinical investigations on netilmicin were performed and results obtained were as follows:
1) Susceptibility of clinically isolated strains to netilmicin was tested by agar plate dilution method and compared to susceptibility to gentamicin.
The minimum inhibitory concentrations of netilmicin for 75% inhibition of P. aeruginosa were less than 0.78μg/ml. Six strains of S. marcescence and one strain of E. coli which showed resistance for GM were sensitive to netilmicin.
2) Of 5 patients treated with netilmicin for respiratory tract infection (3 cases) and UTI (2 cases), clinical results were effective in 3 patients.
No side effects were observed in all of 5 cases by the administration of this drug.

View full abstract

Minimal inhibitory concentrations (MICs) of Netilmicin against a total of 108 clinical isolates of gram negative bacilli were compared with those of the other aminoglycoside antibiotics available at present, those were, Gentamicin (GM), Dibekacin (DKB), Tobramycin (TOB) and Sisomicin (SISO). And therapeutic effect of netilmicin was observed on a patient with infected bronchiectasis.
Of 28 isolates of E. coil examined, 18 (64%) were inhibited at 0.78 μg/ml or less of netilmicin, 19 (68%) at the same concentrations of sisomicin, 16 (57%) at those of gentamicin. Thus, it was apparent that the 3 drugs mentioned above possessed similar antimicrobial activities against E. coli. Dibekacin, tobramycin and amikacin revealed to be 2 to 4 fold less active against E. coil than netilmicin, sisomicin and gentamicin.
More than 60 per cent of 28 tested strains of Klebsiella pneumoniae were inhibited at 0.39μg/ml or less of netilmicin and sisomicin. But 2 fold higher concentration of gentamicin was required to inhibit the same portion of the strains. Amikacin and dibekacin were shown to be less active against E. coli than netilmicin and sisomicin by 1 two-fold dilution, and than tobramycin by 2 two-fold dilutions.
Of 8 clinical isolates of Serratia, 6 were inhibited at 6.25μg/ml or less of netilmicin and these concentrations were 4 times higher than those of gentamicin and sisomicin, and were nearly equal to those of dibekacin, tobramycin and amikacin.
The MICs of netilmicin against 44 clinical isolates of Pseudomonas aeruginosa distributed widely from 1.56 to over than 100μg/ml, but 31 isolates (70%) were inhibited at concentrations ranging from 1.56 to 6.25μg/ml of the drug. Against Pseudomonas, among aminoglycoside antibiotics tested, tobramycin, sisomicin, dibekacin and gentamicin were active, in the order mentioned, than netilmicin. Amikacin was slightly less active than netilmicin against Pseudomonas.
A complete cross resistance was noted between netilmicin and gentamicin. But in contrast, most of clinical isolates of E. coil and Pseudomonas resistant to dibekacin or amikacin wete susceptible to netilmicin. About a half of strains of Klebsiella which were insensitive to dibekacin or amikacin were also sensitive to netilmicin.
A patient, 46 year old female, with infected bronchiectasis was treated with netilmicin at a daily dose of 150mg, divided twice, for 9 day. A favorable clinical response was obtained. The patient became afebrile by the evening of the day of the start of the treatment. Three days after cough and sputum disappeared. Immediately before the treatment, E. coli and H. influenzae had been cultured from the sputum. E. coli was eradicated from the sputum by the treatment. Since despite of persistence of H. influenzae marked decrease in the amount of the sputum was achieved, E. coil was assumed to be the causative organism. Thus, the bacteriological outcome with the netilmicin treatment was considered to be positive in this patient. No abnomality was detected in hepatic and renal function tests and in peripheral blood analysis which were performed at the end of the treatment. No auditory disturbance was proved by making a comparison of the audiograms taken before and after the treatment.

View full abstract

Netilmicin was injected i. m. into the following 25 patients: 15 with respiratory tract infection, 8 with urinary tract infection, and 2 with other infections. Clinical results were excellent in 14, good in 7, poor in 2, and undermined in 2.
No clinical side-effects were observed, while exacerbation of renal dysfunction in an old patient and granulocytopenia in another patient were observed.

View full abstract

Netilmicin was given to 20 patients, 13 with respiratory tract infections and 7 with urinary tract infections. The drug was administered intramuscularly at a daily dose of 150mg or 200mg.
1) Efficacy rate was counted 61% in respiratory tract infections and 71% in UTI. The overall efficacy was 65%.
2) Netilmicin was especially effective to infections by E. coli and Klebsiella and not so effective to infections by P. aeruginosa.
3) Transient elevation of transaminases was noted in one case. Nephrotoxicity and ototoxicity were not noted.

View full abstract

On a new aminoglycoside antibiotic, netilmicin, antibacterial activity against a variety of Gram-negative clinical isolates was determined, and clinical trial on this drug was performed.
The sensitivities of these strains were good in general, but there found almost complete cross resistance between MICs of netilmicin and dibekacin.
Clinically a total of 4 patients including three of respiratory tract and one of urinary tract infections was treated with netilmicin. There was no response in a case of urinary tract infection. In cases of respiratory tract infections, it was evaluated that one was excellent, one was fair and one was poor.

View full abstract

Basic and clinical investigations on netilmicin led to the following results:
MICs of netilmicin were in a range of 0.39 to 12.5 μg/ml, <0.2 to 100<, ag/ml, O.78 to 100<g/ml, O.39 to 6.25μg/ml, 0.78 to 6.25 μg/ml and 6.25 to 100<μg/ml against clinical isolates of E. coli, K. pneumoniae, P. aeruginosa, E. cloacae, C. freundii and S. marcescens, respectively. The antibacterial activity of netilmicin was comparable or slightly superior to those of gentamicin, dibekacin, tobramycin, sisomicin and amikacin against E. coil and K. pneumoniae, while netilmicin was almost equal to these 5 antibiotics in activity against P. aeruginosa.
The serum concentrations of netilmicin following single intramuscular doses of 75mg or 100mg to 3 healthy volunteers peaked at 30 min-1 h with the mean values of 6.3 μg/ml and 10.4μg/ml, respectively, and then decreased to O.4 μg/ml and 1.2 μg/ml, respectively, at 6 h. The respective mean serum half-live were 1.4 h and 1.8 h. Urinary excretion rate of netilmicin during 6 h after intramuscular administration was about 60% in the former and about 80% in the latter.
Netilmicin was given to a total of 13 patients, 4 with respiratory tract infections and 9 with urinary tract infections. Clinical response was satisfactory in 11 cases. Bacteriologically 10 out of 17 causative organisms were eradicated. Tinnitus and elevations of S-GOT and S-GPT were observed in 1 case each during the drug therapy.

View full abstract

The following were results obtained with Netilmicin.
1. Antibacterial activity: The MICs of Netilmicin were almost identical to those of Gentamicin against Klebsiella, Acinetobacter, and Enterobacter, while somewhat higher than those of Gentamicin against P. aeruginosa and Serratia.
2. Absorption Excretion: The blood level of Netilmicin was slightly lower than that of Gentamicin. Dose response was obseved. Similar results were obtained with urinary excretion in comparison with Gentamicin.
3. Clinical results: Netilmicin treatment was poor in two cases with urinary tract infections and good in one case with respiratory tract infection. No side effects were observed.

View full abstract

Investigations on Netilmicin, a newly developed aminoglycoside antibiotic, were carried out to evaluate its antibacterial activity against clinical isolates of gram-negative bacilli, blood levels after repeated administration, and clinical efficacy.
1) The MICs of Netilmicin were compared with those of GM and AMK against 25 strains each of representative bacteria. Netilmicin was as active as GM and slightly superior to AMK against E. coli and K. pneumoniae. Against P. vulgaris, P. mirabilis, and M. morganii, the antibacterial activities of three antibiotics were almost identical. Netilmicin was as active as AMK and slightly superior to GM against S. marcescens. For P. aeruginosa, Netilmicin was as active as AMK and slightly inferior to GM, while a cross-resistance was observed among three antibiotics in highly resistant strains.
2) The determination of blood concentrations of Netilmicin following intramuscular administrations of 75 mg b. i. d. every 12 hours for 8 days demonstrated no accumulation of Netilmicin in the blood.
3) Netilmicin was administered intramuscularly at dose of 75 mg b. i. d. for 7 to 20 days to 11 patients in total, 3 cases with respiratory tract infections and 8 cases with urinary tract infections.
In 3 cases with respiratory tract infections all due to P. aeruginosa, clinical and bacteriological results were good in 1 case and poor in 2 cases. All patients with urinary tract infections were diagnosed as chronic complicated episodes. The causative organism was P. aeruginosa in 7 cases and E. coli in 1 case. The clinical results obtained in these cases were good in 7 cases and poor in 1 case, and the bacteriological results were good in 4 cases, fair in 3 cases and poor in 1 case. No side effects were observed except a transient elevation of GPT in 1 case.

View full abstract

Investigations on a new aminoglycoside antibiotic Netilmicin were carried out to evaluate its pharmacokinetics in geriatric patients and efficacy in the treatment of infections in the field of internal medicine.
Concentrations of Netilmicin in the serum for up to 8 h after 1. m. administration of 75 mg or 100 mg were determined by bioassay in 7 geriatric patients (age, 71 to 92 years; creatinine clearance (Ccr), 106.5 to 3.1 ml/min) and 2 young healthy volunteers (age, 28 and 32 years; Ccr, 93.8 and 98.4 ml/min). High correlation was shown between the elimination rate constant (Kel) calculated by analysis and Ccr with the equation Kel=0.0036 Ccr+0.0563 (r=0.98), while higher correlation was shown between serum clearance (C1B) and Ccr with the equation C1B=0.6807 Ccr+10.1875 (r=0.99). Serum creatinine (S-Cr), serum urea nitrogen, and age were poorly correlated with Kel and Cis, which demonstrated the necessity for determination of the dosage based on Ccr in geriatric patients. The dosage in geriatric patients calculated from pharmacokinetic theory on the basis of usual dose, 100 mg per 8 h, was defined by the formula: dosage (mg per 8 h)=0.88 Ccr+13.20.
Netilmicin treatment in 7 cases with urinary tract infections were excellent in 3 cases, good in 3 cases, and poor in 1 case (efficacy rate, 86%), without side effects, which proved the usefulness of the drug.

View full abstract

MIC of netilmicin was determined on 24 strains of gentamicin-resistant Staphylococcus aureus. 6.3-1.6μ g/ml of netilmicin inhibited S. aureus strains which was moderately resistant to gentamicin MIC of GM ranged from 50 to 12.5 μg/ml, and 50-25 μg/ml of netilmicin was necessary to inhibit the highly resistant S. aureus strains MIC of GM was above 100 μg/ml. Seven cases of chronic complicated infection (three with RTI and four with UTI) were treated with netilmicin. Clinical results were as follows: 2: good, 2: fair, and 3: poor.

View full abstract

Therapeutic effect of Netilmicin, a recently developed new aminoglycoside antibiotic agent, was examined in 22 cases of respiratory tract infection (8 cases of pneumonia and 14 cases of chronic bronchitis).
1. The subjects were mostly middle-aged and senile patients, and 13 cases (59%) had previous complex symptoms, or had experienced treatment with antibacterial agents without success, or had incurable factors.
2. Netilmicin was administered to these cases, and it was effective for pneumonia in 88%(7 effective and 1 non-effective cases out of 8), and for chronic bronchitis in 57%(8 effective and 6 non-effective cases out of 14), and total effectiveness was attained in 69%(15 effective and 7 non-effective cases out of 22).
3. No subjective and objective findings considered as the side effect was observed, and laboratory examinations showed no abnormality.
4. It may be concluded from the above clinical results that Netilmicin may be effective for respiratory tract infections, and further study may prove its efficacy.

View full abstract

Netilmicin sulfate, a new semisynthetic aminoglycoside antibiotic, was injected to 9 patients with urinary tract infection (5 patients) and with respiratory tract infection (4 patients). A daily dose of Netilmicin was 150-200mg by intramuscular injection and duration of Netilmicin therapy was for 7 to 14 days.
The results were as follows.
1. Clinical response to Netilmicin therapy of urinary tract infection was excellent in 2 cases, good in 1 case, fair in 2 cases and that of respiratory tract infection was good in 1 case, fair in 2 cases, poor in 1 case. Effective rate was 44.4%.
2. Netilmicin was especially effective to infections by E. coli and urinary tract infection by P seudomonas aeruginosa.
3. Anemia and thrombocytopenia, as side effects, were observed in one case, but they were all transient. Neither nephrotoxicity nor ototoxicity of Netilmicin were clinically observed.

View full abstract

Laboratory and clinical investigations were carried out on netilmicin, a new semisynthetic aminoglycoside antibiotic, and following results were obtained:
1. Netilmicin exhibited a wide-spectrum growth inhibitory action against gram-positive cocci and gramnegative bacilli, and its antibacterial activity was stronger than that of AMK and GM against Klebsiella and P. aeruginosa.
3. As a side effect, eosinophilia was observed in 2 patients a week after the start of Netilmicin administration.

View full abstract

Netilmicin, 75 or 100 mg, was intramuscularly injected twice daily (morning and evening) to 43 cases. Subjects were 25 cases of acute pneumonia, 7 acute bronchitis, 5 acute aggravation of chronic bronchitis or bronchiectasis, 1 lung abscess, 3 empyema and 2 pyelitis. Clinical and bacteriological efficacies of the antibiotic agent were judged by physicians in charge and all members attending to this project study on the 4 th, 7 th and 14 th day of treatment, and the following results were observed:
1. Efficacy of netilmicin was excellent in 7 cases, good in 23 as judged by physicians in charge, that is, it was effective in 30 cases (76.9%).
2. Efficacy of netilmicin was excellent or good in 58. 5% on the 4th day, in 82. 1% on the 7th day and in 86.4% on the 14th day, as judged by all members attending to the project. It may suggest that Netilmicin should be administered for 7 to 14 days to obtain desirable effects.
3. Netilmicin was effective for the following infections: it's efficacy was excellent in 7 cases and good in 15 cases of acute pneumonia out of 24 cases. Netilmicin was thus effective in 22 acute pneumonia (88. 0%). It's efficacy was excellent or good in 28 (75. 7%) out of 37 cases of respiratory tract infections, and good in 2 cases (100%) of urinary tract infections.
4. Efficacy of Netilmicin was excellent and good in 69.0% of the group complicated with other disease and in 90. 0% of the group without such complications. Netilmicin was effective in 62. 5% of serious and in 79. 5% of moderate cases.
5. Bacteriological test revealed that Staphylococcus spp, Streptococcus spp, and such Gram-negative bacilli as Klebsiella spp, Haemophilus spp, Pseudomonas spp, and E. coli, were isolated in these cases.
Thus, bacteriologically, isolated bacteria eradicated in 14 cases, and decreased in 8 cases, and the total antibacterial effect was 71.4%.
6. Transient increase of GOT and GPT was observed in 1 case, and measles-like drug eruption was seen in 1 case on the 2nd day of administration. Pain at the injection site was complained by 3 patients out of 43. No change in audiogram was found in 27 cases to whom hearing tests were performed before and after the treatment. Thus, no significant side effect was observed by the administration of Netilmicin.
7. Clinical and bacteriological effects as well as side effect were totally evaluated, and the following conclusion was derived: Netilmicin was very useful in 8 cases (19.5%); useful in 23 cases (56.1%) and slightly useful in 7 cases. Total effect of Netilmicin was observed in 38 cases (92.7%) out of 43 cases.

View full abstract

A clinical study was conducted with netilmicin, a new aminoglycoside antibiotic, the 1-N-ethyl derivative of sisomicin, in the treatment of 13 patients with respiratory tract infections.
A favorable clinical response was observed in 54.5% of the patients treated with daily dose of netilmicin ranging from 150mg to 225mg. The drug was administered intramuscularly, divided into 2-3 Edoses, for the period of 5-14 days.
The results obtained were good in six cases, slightly-good in one case, and failed in four cases. One case of pulmonary tuberculosis and one case of adverse effect were excluded.
No marked adverse effects were observed except tinnitus in one case in whom the drug was discontinued after three doses (total 300mg).

View full abstract

Antibacterial activity and clinical effectiveness of netilmicin, a new aminoglycoside antibiotic, were investigated and the results were as follows:
1. In vitro antibacterial activity
Peaks of MICs of netilmicin against various clinically isolated S. aureus, E. coli, Klebsi ella, P. mirabilis, P. vulgaris and P. aeruginosa were 0.2-0.39 izeml, 1.56-3.12 μg/ml, 0.78-1.56 μg/ml, 0.78 μg/ml, 1.56 μ g/ml, 3.12-6.25 μg/ml, at the lower inoculum size, respectively.
Antibacterial activity of netilmicin was comparable or slightly inferior to gentamicin and cross-resistance between netilmicin and gentamicin was observed
2. Clinical results
Netilmicin was administrated by intramuscular injection (i. m.), intravenous infusion (i. v.) or inhalation to 3 cases with respiratory tract infection, 2 with urinary tract infection and 1 with septicemia, at a daily dose of 100-300mg (i. m., i. v.) or 75mg (inhalation). The clinical responses to netilmicin were excellent in 2 cases, good in 2 cases, fair in 1 case and poor in 1 case.
Adverse effect was observed in only one case with eruption.

View full abstract

Netilmicin, a new aminoglycoside antibiotic recently developed by SHERING CO., was examined on its in vitro antibacterial activity, on its blood levels and urinary excretion rates in humans, as well as on its distribution in rat's body. Some clinical trials were also carried out. The results obtained were as follows:
1) In vitro antibacterial activity against bacteria isolated from human infection foci: MICs of the drug against S. aureus strains were distributed from 0.1 to 0.78μg/ml (peak: 0.1μg/ml) similarly to gentamicin (GM), being lower than those of tobramycin (TOB) and amikacin (AMK). Proteus mirabilis and Klebsiella strains were found to be similarly sensitive to Netilmicin, TOB and GM, while, as to E. coli strains, Netilmicin was most active among the aminoglycosides examined. On the other hand, Pseudomonas aeruginosa strain showed least susceptibility against Netilmicin among those drugs. MICs of Netilmicin against Serratia strains were similar to those of TOB as well as AMK, being higher than those of GM.
2) Blood levels and urinary excretion in humans: The average peak blood level of Netilmicin in four adult volunteers after single i. m. injection of 75 mg was found to be 6. 8 μg/ml one hour after the administration. The average urinary excretion rate of the antibiotic during six hours after the administration was 50.4%.
3) Distribution in rat's body: The distribution pattern of Netilmicin in rat's body after i. m. injection of 40mg/kg was similar to those of other aminoglycosides.
4) Clinical trials: Netilmicin was administered (75-100 md i. m., twice a day for 5-11 days) to 14 patients (RTI 5, UTI 8, peritonitis 1). Nine of those patients well responded to the treatment, as far as the causative bacteria were E. coli, Serratia, or Proteus sp. One patient with UTI due to pseudomonas did not respond to the treatment, and, in two of the UTI patients, the pathogens were substituted by Pseudomonas following Netilmicin administration. These clinical results seemed to well coincide with the in vitro antibacterial pattern of the drug.
As to the untoward reactions of the patients to, Netilmicin, neither side effects nor abnormal laboratory findings attributable to the drug were observed, excepting a transient pancytopenia observed in one patient with liver damage.

View full abstract

Basic and clinical studies on Netilmicin, a recently developed new aminoglycoside antibiotic agent, were performed.
1. The test bacteria were isolated from urine specimens with complicated urinary tract infections patients, most of them with spinal cord injury. MIC's of Netilmicin for S. marcescens and P. aeruginosa, 135 strains for each species, were determined. MIC's of Netilmicin were distributed around 12. 5 to 25μg/ml, and mostly between 6. 25 to 100μg/ml. It showed slightly lower MIC's for S. marcescens.
2. No specific relation between the serum type against antigens of the both bacterial strains and the MIC's was found, and various serum types strains showed almost the same susceptibility.
3. Among 5 cases of respiratory tract infections, Netilmicin was effective in 3 cases and slightly effective in 1 case of bronchiectasis with pneumonia. It was not effective in pulmonary abscess with sclerotic cavity.
4. Netilmicin was administered to 3 cases of urinary tract infection for 4 times. It was remarkably effective in 1 case of acute pyelonephritis, and effective in 1 case, not effective in 1 case and the effect not judged in 1 case of complicated urinary tract infections with spinal cord injury.
The last case, in which the effect of Netilmicin could not be judged, showed local swelling and reddness with pain at the site of intramuscular injection, and the administration of Netilmicin was discontinued 4 days later.

View full abstract

Netilmicin was administered to 10 cases of respiratory tract infections, and blood level and thracic fluid level of Netilmicin were determined in time course manner in 5 cases.
The following results were obtained:
1) When Netilmicin was administered alone to 9 cases, it was very effective in 3 cases and effective in 6 cases, that is, 100% of effectiveness was shown.
2) Auditory tests were performed in 6 cases, and no abnormality was found.
3) Hepatic and renal function tests and other laboratory tests showed no abnormality.
4) Change of intramuscularly administered Netilmicin, 100 mg, in thoracic fluid was observed; it reached at the peak level, 1.04μg/ml 4.1 μg/ ml, in 2-3 hours, and the level corresponds to 12.0 54.2% of the maximum blood level.

View full abstract

Laboratory and clinical studies were carried out on Netilmicin, a newly developed aminoglycoside antibiotic which is a derivative of Sisomicin.
Netilmicin was compared with Gentamicin (GM) for antibacterial activity against 378 routine clinical isolates. Netilmicin was found to be similar in activity to GM against Escherichia coli, Klebsiella aerogenes, Enterobacter cloacae, E. aerogenes, Proteus vulgaris and P. morganii. Against Serratia marcescens, P. mirabilis, P. rettgeri and Pseudomonas aeruginosa, Netilmicin was slightly less active than GM.
Netilmicin was injected intramuscularly to two patients with chronic urinary tract infection due to S. marcescens. Both patients had an indwelling catheter. The peak serum concentrations were 17μg/ml and 23.6 μg/ml after administration of 75 mg and 100 mg, respectively.
Netilmicin was excreted into the urine at the concentration of 100-200μg/ml and minimum inhibitory concentration (MIC) of Netilmicin against S. marcescens isolated was 3.13-6. 25μg/ml. Viable count of S. marcescens in the urine was stable during the study for 6-9 hours after injection.
Netilmicin was administered during two separate periods to a patient with chronic bronchitis due to Haemophilus influenzae at the doses of 100 mg and later 200 mg. The peak serum levels after injection of 100 mg and 200 mg were 16.6μg/ml and 19.0μg/ml, respectively. The peak sputum level was around 4μg/ml for both dosages. Haemophilus influenzae in the sputum after intramuscular injection of 200 mg was reduced from 10^7-8/ml at the beginning, to around 10³/ml 5-6 hours afterwards.
Netimicin was given to a total of 16 patients with respiratory and urinary infections. Six out of them responded effectivly to the treatment with efficacy rate of 42.8%. Such a poor clinical result is considered to be attributable to the fact that a majority of patients had severe underlying diseases.
Four out of 18 cases injected had the following adverse reaction, i. e. numbness in the lips, numbness in the face, feeling of vertigo and transient elevation of S-GOT accompanied with that of alkaline phosphatase.

View full abstract

Netilmicin, a new semisynthetic aminoglycoside derived by ethylation of the 1-N position of the deoxystreptamine ring of sisomicin, was tested in vitro with respiratory pathogenic organisms, using the agar dilution method to determine the minimum inhibitory concentraions. Netilmicin was more active in vitro against Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, and Enterobacter species than the other broad-spectrum aminoglycoside antibiotics tested, i. e., gentamicin, tobramycin, dibekacin, and sisomicin; it was less active against Pseudomonas aeruginosa than the other aminoglycosides tested. All the gentamicin-resistant strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter species were resistant also to netilmicin. Synergy of netilmicin with cefoperazone could be demonstrated against respiratory isolates of Pseudomonas aeruginosa.
Concentrations of netilmicin in serum, kidney, liver, and lung were measured with bioassay using Bacillus subtilis ATCC 6633 as the test organism. Accumulation of netilmicin occurred in the kidney; similar results were obtained with sisomicin.
Netilmicin at a dose of 75 mg was infused intravenously over 60 min into the two patients with chronic broncho-bronchiolitis. The peak serum concentrations of the patients were 12. 8 μg/ml and 10.7 μg/ml, the serum half-lives being 120 min and 122 min, respectively. The cumulative urine recoveries of netilmicin expressed as a percentage of the administered dose were 46. 9% at 6h and 50. 4% at 7h after the administration of netilmicin. respectively. The ratios of maximum sputum level to peak serum concentration were 9. 3% and 11. 1%, respectively, in the two patients. In one of them, the intrabronchial levels of netilmicin were ranged from 2.0 to 2.7μg/ml, which were approximately threefold higher than the expectorated sputum level of netilmicin.
Six pseudomonal respiratory infections and six gram-negative bacillary urinary tract infections were subjected to clinical evaluation of netilmicin. Four respiratory infections were treated with combination of netilmicin and either cefotaxime, cefoperazone, cefsulodin, or lincomycin. Clinical responses were good in one, fair in three, and poor in two of six respiratory infections; an excellent or good clinical response was observed in all of six urinary tract infections. No adverse effects were observed in 12 cases in this series.
The data indicate that netilmicin is one of the most effective and useful broad-spectrum aminoglycoside antibiotics for the treatment of respiratory bacterial infections.

View full abstract

Basic and clinical characteristics of recently developed Netilmicin were investigated, and the following results were obtained.
1) Antibacterial potency: Antibacterial potency against the Gram positive bacteria, such as S. aureus was less than GM in 1 tube dilution. It was almost the same as GM against the Gram negative bacteria, E. coil, E. cloacae, and Proteus strains. It was slightly less than GM against K.pneumoniae, P. aeruginosa and Serratia.
2) Levels in tissues: Blood level of Netilmicin reached the maximum value in 30 minutes after the administration to 11. 5 and 12.5μg/ml, and no Netilmicin was detected 8 hour after the administration.
3) Clinical effects and adverse effect: Netilmicin, 150-225 mg per day, administered to 14 cases of respiratory tract infections (including 7 cases of bronchopneumonia, 1 case of pneumonia, 1 case of pneumonia purulenta, 1 case of thoractic purulenta, 3 cases of bronchiectasis, and 1 case of chronic bronchitis) and 1 case of urinary tract infection for 6-24 days, and it was effective in 87 % of these cases.
Local pain was induced in 1 case as a side effect of Netilmicin, but laboratory analysis showed no abnormal values.

View full abstract

Fundamental studies were made on netilmicin, a new aminoglycoside antibiotic, and the following results were obtained.
The MICs of 205 strains of various gram-positive and-negative organisms derived from the clinical isolates were almost equal or slightly superior to those of gentamicin. When the relationship between the MIC of netilmicin and that of gentamicin was evaluated as to 70 strains of P. aeruginosa, an almost coniplee cross resistance was recognized.
Passage of netilmicin into CSF was evaluated in experimental staphylococcal meningitis in 8 rabbits. After a single intramuscular injection of 5 mg/kg of the drug, the following parameters were determined at 1/2hr, 1 hr, 1 1/2 hr and 2 hrs, respectively. Blood concentrations were 20±0.82μg/ml, 13.7±1.28μg/ml, 10.5±0.97μg/ml and 7.72±1.08μg/ml; CSF concentrations, 1.33±0.19μg/ml, 1.80±0.30μg/ml, 1.93±0.32μg/ml and 2.02±0.33μg/ml; CSF/serum ratio, 6.5%, 13.1%, 18.4% and 26.2%, respectively.
Among the aminoglycosides so far tested, the above results with netilmicin was the best as to the CSF concentration of the drug and the third in CFS/serum ratio, thus indicating a good passage into CSF. However, it was considered difficult to treat bacterial meningitis only with systemic administration of netilmicin.
When these results were taken into consideration with a reported low incidence of oto and nephrotoxicity, netilmicin appears to be a new aminoglycoside worth being clinically tried in children, although the problem of neuromuscular blockage should be kept in mind.

View full abstract

During clinical trials with Netilmicin the following results were obtained:
1. Netilmicin in a daily dose of 150 mg to 200 mg was administered to 4 adult patients which were empyema, lung absess and chest wall abscess.
2. Clinical response were good in 3 cases, fair in 1 case.
3. No side effects were observed or reported.

View full abstract

Netilmicin was administered to 4 patients with postoperative infections which were perineal abscess, pneumonia and peritonitis.
Clinical responses were good in all cases. Bacteriologically, gram negative bacteria were isolated from a pus and sputum.
No side effects were observed in all cases.

View full abstract

Basic and clinical investigations on netilmicin led to the following results.
1) Netilmicin showed the most excellent antibacterial activity among the aminoglycosides tested againstE. coli, and, to a lesser extent, against S. aureus, K.pneumoniae, Enterobacter, S. marcescens, and P. aeruginosa.
2) Serum and urinary concentrations of netilmicin following an intramuscular dose of 75 mg to 3 healthy adult volunteers were determined by cup method using B. subtilis ATCC 6633 as the test organism. The, mean peak serum concentration of 6. 07μg/ml occurred at 30 min after administration. Urinary concentration attained a peak at 1 hr after administration with the mean value of 385μg/ml, and mean urinary excretion rate during 6 hours was 78.1%.
3) The pharmacokinetic parmeters derived from the serum concentrations, based on one-compartment open model, were as follows: Kel (hr^-1), 0.44; 1/2 T (hr^-1), 1.56; Vd (L), 13.4; and AUC (μg hr/ml), 5.86.
4) Tissue levels in SD rats given an intramuscular dose of 20 mg/kg were the highest in the serum, followed by the kidney and lung.
5) The results of bioautogram of human urine obtained by thin-layer chromatography revealed that netilmicin was excreted into the urine unchanged.
6) Netilmicin treatment in 11 cases with surgical infections was excellent in 1 case, good in 6 cases, fair in 1 case and poor in 3 cases, with efficacy rate of 63. 6%. No serious side effects were observed.

View full abstract

Fundamental and clinical studies of netilmicin in the surgical fields were performed and following results were obtained.
(1) Antibacterial activity: To E. coli and Klebsiella isolated from surgical material, netilmicin had the same antibacterial activity as gentamicin. Against Pseudomonas aeruginosa its activity lied between gentamicin and amikacin.
(2) Clinical results: Netilmicin was administered to two patients with surgical infection and the results were good in one case and poor in another. No side effects could be found.

View full abstract

Antibiotics of the aminoglycoside group are indicated in the treatment of peritonitis when the spectrum of pathogenic microorganisms is taken into consideration. We studied the penetration into peritoneal fluid and the clinical usefulness of Netilmicin, an aminoglycoside with low nephro- and ototoxicity.
1. Twenty patients with acute purulent peritonitis were intramuscularly given 100 mg of Netilmicin twice daily over periods of time between 3 and 9 days (mean, 5. 8 days). The clinical response was excellent in 4 patients, good in 12 fair in 2, and nonevaluable in 2, the efficacy rate (excellent plus good/evaluable) being 88. 9%. However, postsurgical wound infections occurred in 3 patients.
2. Pathogens were isolated from ascites in 15 patients. Infections were monomicrobial in 12 patients: E.coli was isolated in 9, and Klebsiella, Acinetobacter and B. fragilis in one, respectively. Three patients had polymicrobial infections due to E. coli and other species of bacteria. Susceptibility testing to Netilmicin revealed the MIC less than 3.2μg/ml for each of these isolates. The pathogenic microorganisms disappeared after administration of Netilmicin in each patient. Subsequently, however, detected in 3 patients were strains of E. coli, Streptococcus faecalis, Serratia and Flavobacterium showing the MIC of 6.25 μg/ml or greaterthan 100μg/ml.
3. Peak concentrations ranging from 3. 15/tend to 4. 3/2g/ml were attained in peritoneal fluid one to three hours after intramuscular injection of 100 mg of Netilmicin. The antibiotic was still detected in concentrations around 1μg/ml at 8-12 hours. In patients receiving Netilmicin at 100 mg every 12 hours for 5-7 eays, a mean concentration of the antibiotic in peritoneal fluid was 2.45±0.34μg/ml. The concentrations of Netilmicin in peritoneal fluid collected from all patients showing excellent or good responses always exceeded the MIC for respective pathogens.
4. Transient leukopenia occurred in one patient and diarrhea in another in association with the Netilmicin therapy. Neither symptoms and signs nor laboratory data indicating nephro- and ototoxicity were observed in any patient.
5. In conclusion, Netilmicin is useful in the treatment of peritonitis.

View full abstract

Netilmicin, a new semisynthetic aminoglycoside, is a 1-N-ethyl-Sisomicin derived from Micromonospora inyoensis. Its antimicrobial spectrum is similar to that of gentamicin. Animal studies indicate that netilmicin is less ototoxic and nephrotoxic than gentamicin.
The drug was administered to 19 patients with surgical infections, such as respiratory tract infections, cholecystitis, peritonitis, abdominal wall abscess, infectious fistula, wound infections, periproctal abscess, urinary tract infection and sepsis.
The results obtained were excellent in 3, good in 12, fair in 1 and poor in 3 patients (efficacy rate: 78.9%). Particularly satisfactory results were seen in peritonitis, periproctal abscess and sepsis.
Among untoward side-effects, there were seen tinnitus in one case, liver dysfunction (increased GOT, GPT and Al-P) in 2 cases and increased BUN in one case.

View full abstract

Investigations on a new aminoglycoside antibiotic Netilmicin were carried out to determine the concentrations in the serum, urine and bile, and to evaluate therapeutic effects in the field of surgery.
Serum concentration of Netilmicin attained a peak at 2 h after an intramuscular dose of 100 mg with the mean value of 5.48μg/ml. Thereafter, the level gradually declined to undetectable range at 24 h. The mean peak urinary concentration, occurring at 2 h. after dosing, was 3.00μg/ml. No detectable amount of drug was excreted in the urine at 24 h.
Biliary excretion was determined in 3 patients undergoing PTCD. The peak biliary concentrations were 2.60μg/ml at 2 h after dosing in Case 3, 1.76μg/ml at 1 h in Case 2, and 1.51μg/ml at 3 h in Case 1, respectively. No detectable amount of drug was excreted in the bile at 24 h.
There was no accumulation of Netilmicin in the blood after intramuscular administrations of 100 mg once or twice a day for 3 to 4 days.
Netilmicin was given intramuscularly at dose of 75 mg or 100 mg b. i. d. for 4 to 14 days to a total of 7 patients with severe underlying disease, 5 with wound infection and 1 each with cholangitis and pyothorax. The clinical response was good in 6 cases, and poor in 1 case, with efficacy rate of 85.7%. Bacteriologically, causative organisms were eliminated except one P. aeruginosa and one grampositive bacterium. No side effects were observed except a slight elevation of GOT in 1 case. It appears from this study that Netilmicin is an effective drug for the treatment of infections in the field of surgery.

View full abstract

In 25 hospitalized patients with complicated urinary tract infections, a favorable clinical response was observed in 24 96 of the patients treated with a dose of Netilmicin ranging from 75 mg to 200 mg per day for 5 days.
The initial infecting organisms persisted in 17 patients.
In the present study no major side effects were observed except a rise in S-GPT in one case. Of 13 patients who had audiometric studies, no one had ototoxicity.

View full abstract

Antibacterial activity and clinical effectiveness of Netilmicin, a new aminoglycoside antibiotic, were examined, and the following results were obtained:
1) Netilmicin was most active against E. coli, Vibrio Parahaemolyticus, and Francisella tularensis, approximately one tube less active than GM against S. marcescens, and one to two tubes less active than GM, TOB, and DKB against P. aeruginosa.2) Twenty pts with UTI received intramuscular injection of Netilmicin for 5 consecutive days.
Clinical results judged by physicians were excellent in 3, good in 1, fair in 6, and poor in 9. In CUTI, clinical effectiveness judged by the criteria proposed by UTI Research group was, good in 4 and poor in 13. No adverse reactions were observed other than GOT and GPT elevation in one case.

View full abstract

Basic and clinical studies on Netilmicin, a newly developed aminoglycoside antibiotic, resulted in the following:
1) Most of the E. coli, K.pneumoniae, P. mirabilis, indole-positive Proteus and P. aeruginosa isolates from the urinary tract were sensitive to Netilmicin, showing a same tendency to GM and AMK.
2) The results obtained in 27 cases with complicated urinary tract infections were excellent in 3, good in 10 and poor in 14 cases, with efficacy rate of 48. 1%. There was relationship between the dosage of Netilmicin and the occurrence of favorable responses, since the efficacy rate in 150 mg/day group was 40.0 %, and that in 200 mg/day group 58.3%.
3) Neither subjective symptoms nor abnormal laboratory findings related to the drug were observed.

View full abstract

The following are results of Netilmicin treatment in 24 cases with cornpicated urinary tract infections.
1. The clinical response was excellent in 1 case, good in 13 cases, and poor in 8 cases, with efficacy rate of 63.6 %.
2. There was a possible relationship between the daily dosage and the frequency of favorable responses, since the efficacy rate in 200 mg/day group was higher than that in 150 mg/day group.
3. No side effects such as hepatic, renal, and auditory impairments were observed except generalized skin rash in one case.
4. All strains with MIC of 6. 25 μg/ml or less were eradicated.

View full abstract

Therapeutic experience with netilmicin was performed 11 times to 10 aged subjects with complicated urinary tract infections. The antibiotic agent exerted excellent antibacterial effect on various strains of pathogenic bacteria except some strains of Serratia and Pseudomonas in urine, and eradication of the pathogenic bacteria was seen in 66. 7%, and no appearance of other bacteria was observed during the administration period of netil micin. On the other hand, pyuria was not normalized in any cases, and only 1 case was improved. There was no excellent case, and 4 moderate and 7 poor cases, and 36. 4% of effective rates, were obtained as the clinical results.
Daily dose of netilmicin was 150 mg in 8 cases and 200 mg in 3 cases, and no difference in effect was observed within the above dosage range.
No side effect was observed clinically, and laboratory findings suggested no adverse effect.

View full abstract

Laboratory study on Netilmicin, a recently developed aminoglycoside by Schering and Co., U. S. A., were performed by intramuscular injection of 75 mg or 150 mg of Netilmicin to 2 healthy volunteers for each dose. The peak bloodlevel of Netilmicin was attained in 1 hour after the injection, showing 4. 75μg/ml and 10.70μg/ml, respectively. Urinary recovery during 8 hours was 80.3% and 67. 5%, respectively.
Clinical study was performed in 16 cases of complicated urinary tract infections; that is, 75 mg or 100 mg of Netilmicin was administered twice daily for 5 days. Out of 16 cases, the effect of Netilmicin could be judged by the UTI criteria in 12 cases; 2 excellent, 5 moderate and 5 poor cases (58. 3% of effective rates) were observed. Bacteriologically, Netilmicin was effective against 2 P. aeruginosa out of 3 and 2 Enterococci out of 3, and as a total effect, 21 strains out of 24 were eradicated by the antibiotic, 87. 5% of erradication rates. No side effect due to Netilmicin was observed.

View full abstract

Netilmicin, a new broad-spectrum semisynthetic aminoglycoside, was evaluated for the treatment of chronic complicated urinary tract infections. Twenty-eight patients injected intramuscularly 100 mg of netilmicin twice a day, and treated for 5 days. The clinical effect for 28 cases of chronic urinary tract infections (6 chronic pyelonephritis and 22 chronic cystitis) included 11 excellent cases, 5 moderate cases, and 12 poor cases, the overall effective rate being 57. 1%. No marked side effects were observed.

View full abstract

Netilmicin, a new aminoglycoside antibiotic, was studied both bacteriologically and clinically in the urological field and following conclusions were obtained.
1) MICs of netilmicin for 52 strains of urinary P. aeruginosa were nearly equal to those of GM and AMK. But some strains for which MICs of GM were 100μg/ml or more were relatively sensitive to netilmicin. Strains for which MICs of GM and netilmicin were 100 μg/rnl or more had a tendency to be sensitive to AMK.
2) A peak serum concentration of 5.6μg/ml was achieved 1 hour after intramuscular injection of 75mg of netilimicin in a healthy volunteer and the half-life was 1.47 hours. Urinary peak concentration of 39.8 μg/ml was achieved 1 hour after administration of 75mg intramuscular dose and urinary recovery rate within 67hours was 36.0%.
3) Ten cases of complicated UTI were treated with netilmicin at the dose of either 75mg or 100mg twice a day for 4 to 5 days. Overall clinical efficacies of treatment were excellent in 2 cases (18%) and poor in 9 cases. Of the 26 strains isolated, 15 strains were eradicated. MICs of netilmicin for eradicated strains were 25 μg/ml or less.
4) No side effects attributable to netilmicin treatment were observed.

View full abstract

Basic and clinical effects of Netilmicin, a new aminoglycoside antibiotic were examined. Against clinical isolates from the patients with urinary tract infections hospitalized in our department minimum inhibitory concentrations of Netilmicin in comparison with those of GM and AMK were measured. With inoculum size of 10⁸/ml the sensitivity peaks for Netilmicin were found at ≤0. 2 μg/ ml for Klebsiella, O. 78 μg/ml and 3.1 μg/ml for Pseudomonas, ≤0. 2 μg/ml for Enterobacter and 6. 25 iterril for P. vulgaris, and the MICs of Netilmicin were superior twice to GM, and twice-8 times to AMK. The MICs of Netilmicin were the same as those of GM, superior 4 times to AMK for P. mirabilis, inferior 4 times to GM for E. coli and Serratia, and showed similar to AMK. With inoculum size of 10⁶/ml, the sensitivity peaks for Netilmicin were found at ≤0. 2 μg/ml for Klebsiella, Enterobacter, and P. vulgaris, and the MICs of Netilmicin were superior 4-8 times to GM, and 4-16 times to AMK. The MICs of Netilmicin for Serratia and Pseudomonas were the same as those of GM and superior 4 times to AMK, but for E. coli theywere inferior 4 times to GM and the same as those of AMK.
By intramuscular administration of 100 mg of Netilmicin and 60 mg of GM, their blood levels and the rate of urinary excretion were examined by a cross over method. It was found as the results that the peak blood level attained at 30 minutes after injection to 5 μg/ml for Netilmicin and 5.4 μg/ml for GM, and after 8 hours of the injection, blood levels of 0.57 μg/ml for Netilmicin and 0.36 μg/ml for GM were observed. In 8 hours after the injection, total urinary excretion of Netilmicin was 81% of dose and that of GM was 71%.
A daily dose, 200 mg, in 2 divided doses, of Netilmicin was intramuscularly injected for 5 days to 23 cases of complicated urinary tract infections in order to examine its clinical effects. According to the UTI criteria for clinical evaluation in complicated UTI, among 23 cases 3 remarkably effective, 10 effective and 10 noneffective cases, with 57% of effectiveness, were observed.
Considering bacteriological effect 21 strains out of 30 disappeared, with 70% of eradicated ratio. All strains of E. coli (4 strains), E. cloacae (4 strains), K. pneumoniae (3 strains), and C. freundii (3 strains) disappeared by Netilmicin administration.
One case showing abnormal GOT and GPT values before the administration of Netilmicin showed increase of GOT and GPT values after its administration, whereas in other 22 cases, no abnormalities in BUN, creatinine, GOT, GPT and Al-p values were observed. Otherwise no side effects including general hematological findings and auditory sence were shown in any of all cases.

View full abstract

1) Netilmicin was administrated intramuscularly at a dose of 150 mg or 200 mg per day for 5 days to 24 inpatients with complicated urinary tract infection.
2) The clinical results obtained were excellent in 7 cases (29.2%), moderate in 8 cases (33.3%) and poor in 9 cases (37.5%), the effectiveness rate being 62.5%.
3) In bacteriological results, there were eradication of causative organismsin 16 (53.3%) and persistence in 14 (46.796) out of 30 strains.
4) No side effects were observed in this series.

View full abstract

1. Minimal inhibitory concentration of Netilmicin was determined by plate dilution method on 122 strains isolated from urinary tract infections. Netilmicin exhibited good antibacterial activity against S. aureus, E. coli and P. mirabilis. Most strains of P. vulgaris, Serratia and P. aeruginosa were inhibited at 12.5μg/ml or less, but some of those strains were not inhibited at 100μg/ml at 10⁶ cells/ml inoculum size. When antimicrobial activity was compared with Gentamicin, Netilmicin was superior to Gentamicin against E. coli, but inferior against Serratia and P. aeruginosa.
2. Single dose of 75 mg intramuscularly was administered to a healthy male volunteer. The maximal serum level of 6.8 μg/ml was measured at 30 minute after injection. The urinary recovery rate was 64.1% within 6 hours.
3. Twenty nine cases with complicated UTI were treated with Netilmicin. The therapeutic efficacy was evaluated in 25 cases, ‘Excellent’ and ‘Moderate’ results were obtained in 4 cases.
4. Side effects were observed in 2 cases of this series, those were pain at injected site and elevation of AL-P.

View full abstract

Netilmicin was administered twice daily to 9 cases with complicated urinary tract infection at a dose 100 mg intramuscularly for 5 days. The clinical efficacy was good in 4 cases and poor in 5 cases. Overall effectiveness rate was 44.4%.
No side effect was observed.
2) The serum half-life was prolonged and urine concentration and recovery rate of netilmicin from patients were decreased according to the degree of impaired renal function.

View full abstract