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PubMed1986

In vitro aminoglycoside resistance of gram-negative bacilli and staphylococci isolated from blood in Sweden 1980-1984.

The in vitro susceptibility to gentamicin, tobramycin, amikacin and netilmicin in septicaemia isolates was followed during 1980-1984 in 6-8 Swedish laboratories. The bacterial distribution was similar over the years and was dominated by Escherichia coli and staphylococci. Resistance to gentamicin was found in 2.3-3.6%, to tobramycin in 1.4-3.4%, to amikacin and netilmicin in 0.5-0.9%. Production of aminoglycoside modifying enzymes was observed among resistant strains.

Amikacin↗
PubMed1992

Once daily aminoglycoside dosing: maintained efficacy with reduced nephrotoxicity?

Animal studies report equal or greater clinical efficacy with once daily versus multiple daily aminoglycoside dosing; however, results are inconsistent. Extrapolation of these animal data to human data is difficult, since marked variability exists in terms of pharmacokinetic disposition of aminoglycosides. Human data suggest that once daily aminoglycoside dosing regimens are as effective as multiple dosing regimens. However, studies need to be performed assessing the efficacy of once daily aminoglycoside dosing for infectious sites other than intra-abdominal and the urinary tract. In addition, the results of these studies should not be extrapolated to those with renal dysfunction, the immunocompromised, or in patients with aminoglycoside treatment durations of greater than 8 days, as the efficacy of once daily dosing in these patient populations has not been proven. Animal studies assessing nephrotoxicity suggest that multiple daily aminoglycoside dosing results in more frequent or more severe nephrotoxicity compared to once daily dosing. Nine human studies have been published comparing the nephrotoxicity of once daily versus multiple daily aminoglycoside dosing. The majority of investigators have studied nonimmunocompromised patients with urinary tract infections. Netilmicin has been the most frequently used aminoglycoside, although other agents such as gentamicin, amikacin, and sisomicin have been studied. The most common netilmicin dosage regimen has ranged from approximately 4 to 6 mg/kg administered once daily. Eight of the nine trials performed have documented no significant differences in serial serum creatinine concentrations between once daily and multiple daily aminoglycoside dosing regimens, by the end of the study period. In conclusion, preliminary data suggest that once daily aminoglycoside dosing in nonimmunocompromised patients is equally efficacious and nephrotoxic compared to multiple daily dosing regimens.

Animals↗
PubMed2003

Comparative vestibulotoxicity of different aminoglycosides in the Guinea pigs.

The histopathological alterations in the vestibule due to aminoglycosides are well defined. Although there are reports comparing the vestibulotoxic effects of the many aminoglycosides, this is the first study to compare the effects of the most commonly used aminoglycosides i.e., streptomycin, gentamicin, amikacin and netilmicin administered both transtympanically and systemically. The transtympanic and systemic administration of each aminoglycoside caused similar histopathological alterations in the vestibule. The most severe degeneration in the cristae ampullaris, utriculus and sacculus was observed after streptomycine administration. The severity of the vestibular damage in terms of magnitude was in the order of streptomycine, gentamicin, amikacin, and netilmicin.

Amikacin↗
PubMed1982

Studies of a potential in vitro test for estimation of toxicity of aminoglycoside antibiotics and polyamines.

The electrophoretic mobility of phosphatidyl inositol liposomes at pH 7.4, 25 degrees C, was reduced by aminoglycoside antibiotics, neamine and several polyamines in general accordance with the number of amino-groups on each molecule. There was good agreement between the relative position of the tested compounds on the mobility-concentration graph and available information about their relative mammalian toxicities in vivo. The slope of the graph for netilmicin was distinctively flat; a comparatively flat dose-response curve for netilmicin has been reported also from in vivo studies of nephrotoxicity. Investigation of a homologous series of alpha,omega straight chain diaminoalkanes revealed that hydrophobicity did not contribute significantly to the observed interaction in this system. L-Lysine showed the weakest effect amongst all compounds tested, supporting the view that the overall positive charge on the molecule was the major determinant of the observed effect. Further structure-activity work is required to confirm whether this 'in vitro' test is predictive of the toxicity of aminoglycoside antibiotics in man.

Aminoglycosides↗
PubMed1993

Clinical study of interaction between rocuronium and some commonly used antimicrobial agents.

The onset and duration of clinical relaxation and reversibility of rocuronium bromide (ORG 9426) 0.6 mg kg-1 were studied following administration of netilmicin 2 mg kg-1 (n = 10) or cefuroxime 20 mg kg-1 (n = 10) in patients undergoing urological surgery; and cefuroxime 20 mg kg-1 (n = 10) metronidazole 7.5 mg kg-1 (n = 10), metronidazole 7.5 mg kg-1 and cefuroxime 20 mg kg-1 (n = 10), or placebo (n = 10) in patients undergoing abdominal surgery under anaesthesia with thiopentone, nitrous oxide in oxygen, fentanyl and halothane. The antimicrobial agents were administered intravenously 5 min before rocuronium. Neuromuscular function was monitored using mechanomyography and train-of-four (TOF) mode of stimulation. Onset of neuromuscular block occurred in approximately 60 s with all patients achieving complete block. The mean clinical duration (+/- SD) was 50 +/- 10.7 and 44 +/- 6.7 min following netilmicin and cefuroxime respectively in patients undergoing urological surgery; and 49 +/- 13.7, 44 +/- 11.1, 48 +/- 11.1 and 38 +/- 7.3 min in the groups undergoing abdominal surgery receiving cefuroxime, metronidazole, cefuroxime and metronidazole combination and placebo respectively. There were no statistically significant differences between the groups in either the onset or the duration of clinical relaxation. Reversal of neuromuscular block with neostigmine carried out at spontaneous recovery of T1 (first response in the TOF) of 25% or more was easily achieved in all groups in 2-4 min. It is concluded that there is no significant interaction between rocuronium and single doses of the antimicrobial agents used in the present study.

Adolescent↗
PubMedDate not supplied

Invitro comparative evaluation of aminoglycosides at a cancer centre.

A comparative study of in vitro activity of amikacin, gentamicin, netilmicin, tobramycin and isepamicin was done. A total of 200 clinical isolates of Gram negative organisms from various clinical sources were tested. E.Coli was the most frequently isolated organism followed by Pseudomonas spp., Klebsiella spp., Proteus spp., Acinetobacter spp. and Enterobacter spp. Of the 5 aminoglycosides tested, isepamicin showed the highest numbers of susceptible isolates followed by amikacin, netilmicin, gentamicin and tobramycin. MIC 90 value of isepamicin was lower as compared to amikacin.

Acinetobacter↗
PubMed2003

Kinetics of antibiotics release from ceramic implants.

Presented study describes kinetics of antibiotics release: cefazolin, gentamicin, netilmicin and vancomycin, from two types of ceramic implants: corundum and apatite cement prepared for osteosurgery. The experiments was based on our experimental model developed previously, in which the extraction of antibiotics from implants to polyurethane sponge was made for 3 days. The concentrations of antibiotics in the sponges were determined by spectrophotometric and biological methods. Among all ceramic materials tested, corundum implants with netilmicin and cement implants with gentamicin proved to be most efficacious regarding antibiotics release within 3 days of extraction to polyurethane sponge (yield of the release was 50% and 80% respectively). The lowest release was obtained in the case of cefazolin from cement disks (yield about 0.02%). The kinetics and effectiveness of antibiotics release from the ceramic implants tested depended on ceramic carrier and kind of the drug.

Aluminum Oxide↗
PubMedDate not supplied

Ceftriaxone/metronidazole is more effective than ampicillin/netilmicin/metronidazole in the treatment of bacterial peritonitis.

In a prospective, open, controlled clinical study, 190 consecutive patients who were thought to have bacterial peritonitis before operation, were randomised to antibiotic treatment during and after operation with either ceftriaxone 1 g plus metronidazole 1.5 g once daily (n = 94) or ampicillin 2 g plus netilmicin 150 mg twice daily plus metronidazole 1.5 g once daily (n = 96). Incisional and deep surgical wound infections, postoperative pneumonia and urinary tract infection as well as deaths caused by infection were recorded. Ceftriaxone-metronidazole was significantly more effective than ampicillin-netilmicin-metronidazole, 6/94 wound related infections (6%) compared to 18/96 (19%) (p = 0.02). In patients with peritonitis caused by a perforated colon or appendix the rates of clinical failure were 6% and 28%, respectively. We consider ceftriaxone plus metronidazole an efficient and easily administered antibiotic regimen in patients with bacterial peritonitis, and both the wide range of activity against Gram-negative aerobic rods and the long half life of ceftriaxone seem to be beneficial.

Adolescent↗
PubMed1990

Assessment of antimicrobial penetration into the pancreatic juice in dogs.

The pancreatic ductal penetration of piperacillin, cefuzonam, fosfomycin and netilmicin, injected intravenously, was studied in four dogs with chronic pancreatic fistula. Serum and pancreatic juice were collected simultaneously, frozen, and later assayed for antibiotic concentration. Each antibiotic achieved its therapeutic serum level. The pancreatic ductal levels of piperacillin and cefuzonam were therapeutic, in contrast, the fosfomycin and netilmicin levels were subtherapeutic. These results are considered to be of interest in prevention and treatment of pancreatic infections.

Animals↗
PubMed1990

[Antimicrobial prophylaxis in urologic surgery].

To evaluate the efficacy of preoperative antibiotic prophylaxis, we studied 130 patients who were submitted to prostate surgery. These patients were divided into 3 groups. Overall morbidity was lower for the patient group that had received antibiotic prophylaxis (Netilmicin, 3 doses) than for the group on placebo and the group on antibiotics postoperatively. The incidence of significant bacteriuria for the group on Netilmicin was less at 7 days (7.5%) and at 30 days (20.5%) than for the other groups: (22.55%) and (49.36%) at 7 and 30 days, respectively. The foregoing data indicate that preoperative antibiotic prophylaxis should be used for periods less than 24 h in all noninfected patients undergoing prostate surgery. The cost of antibiotic therapy, presence of opportunistic organisms and the duration of hospital stay are reduced by antimicrobial prophylaxis.

Humans↗
PubMed1989

[In vitro effect of antibiotics against hospital strains of Acinetobacter baumanii].

A total of 142 Acinetobacter baumanii strains isolated from hospital patients were biotyped according to the scheme of Bouvet and Grimont. Most of the strains belonged to biotype 9 and were highly resistant to antibiotics including cephalosporins and amikacin. Imipenem and ticarcillin were the only drugs having a bactericidal activity against A. baumanii. The combination imipenem-netilmicin and ticarcillin-netilmicin were more rapidly bactericidal than imipenem or ticarcillin alone. No resistant strain to imipenem was isolated.

Acinetobacter↗
PubMed1988

Development of gentamicin resistance in gram-negative bacteria in Czechoslovakia and correlation with its usage.

Widespread use of gentamicin in Czechoslovakia began in 1975 when it became more available, although its use remained restricted until 1986. Starting in 1980 a remarkable increase in gentamicin resistance was observed in Pseudomonas aeruginosa, Klebsiella, Enterobacter and several Proteus species, especially Proteus rettgeri. A large proportion of gentamicin-resistant strains came from the urine of hospitalized patients. In spite of infection control measures and restrictive antibiotic policy, gentamicin resistance has increased over the last years. In 1985 gentamicin resistance of bacteria in Czechoslovakia represented 18.2% and was higher than in Austria or the Federal Republic of Germany, for example, but lower than in Hungary, France, Greece and Italy. The usage of gentamicin has also increased. During the years 1982-1987 gentamicin usage in Czechoslovakia increased by one-half. In a representative collection of 69 gentamicin-resistant Gram-negative strains from seven regions of Czechoslovakia, the mechanisms of resistance to gentamicin, netilmicin, tobramycin and amikacin were studied. Production of acetyltransferases (AAC) and adenylyltransferases (ANT) was observed in 84% of strains. The majority of isolates produced AAC(3) enzymes (55%); production of ANT(2") represented the second most observed resistance mechanism (35%); only 14% of isolates produced AAC(6'). This resistance pattern correlates with patterns reported recently for Central and Southern Europe. Due to dissemination of plasmids coding for the AAC(3)-II enzyme, the majority of Czechoslovak gentamicin-resistant Gram-negative strains were also tobramycin- (87%) and netilmicin-resistant (68%). Amikacin remains the most effective aminoglycoside against multiresistant bacterial strains.

Acetyltransferases↗
PubMed1988

[A mathematical study of the mortality curve of Escherichia coli exposed to aminoglycosides].

The time killing curves of three strains of E. coli (CIP54117, ATCC25922 and ATCC29194) exposed to kanamycin, amikacin, netilmicin and dibekacin are decreasing exponentials. The absolute value of the killing rate m is related to the antibiotic concentration through a Michaelis-Henry equation. A maximum killing rate m max and an affinity constant Kc between bacteria and antibiotic can thus be estimated. m max is mainly strain dependent. On the contrary, Kc is related to the antibiotic. Kc is much higher (i.e. the affinity is much lower) for kanamycin and amikacin than for netilmicin or dibekacin. The dose-effect curve is a saturation curve. Increasing doses of antibiotic do not increase the mortality proportionally.

Amikacin↗
PubMed1986

In vivo effect of aminoglycoside on Pseudomonas aeruginosa in experiment.

In artificial pseudomonas infections undertaken on white mice the effectiveness of the aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin) was compared. The most effective drugs on highly susceptible Ps. aeruginosa were amikacin and netilmicin. Moreover amikacin is probably capable of inhibiting pseudomonas toxin production. Therefore this preparation should be left in reserve for the treatment of serious pseudomonas processes.

Amikacin↗
PubMed1987

[Comparative evaluation of the antibacterial activity of aminoglycosides by means of microcalorimetry].

Possible use of microcalorimetry for comparative investigation of antibiotics is exemplified by estimation of the kinetics of the antibacterial effect of netilmicin, sisomycin and gentamycin sulfate on moderately sensitive strains of E. coli and P. aeruginosa. It is suggested that the area under the curve of the kinetics of the rate of heat release by the bacterial cultures in the presence of antibiotics be used as a parameter characterizing the integral antibacterial effect. The parameter was used for demonstrating the differences in the antibacterial action of netilmicin, sisomycin and gentamycin sulfate on the strains tested with application of various inoculum sizes and antibiotic concentrations.

Aminoglycosides↗
PubMed1988

[Comparative bactericidal kinetics of ciprofloxacin, ofloxacin and pefloxacin alone and in combination against strains of group D Streptococcus].

Killing curves method was used to study bactericidal activity of the three quinolones, alone and in combination with penicillin, amoxicillin, fosfomycin, netilmicin, vancomycin against six isolates of enterococci. Alone, ofloxacin showed the most initial bactericidal effect but ciprofloxacin was the most frequently bactericidal without any regrowth in 24 hours. The combinations with beta-lactams and netilmicin were sometimes synergistic in 24 hours; fosfomycin increased initial bactericidal effect.

Amoxicillin↗
PubMed1986

Antimicrobial activity of cefotiam combinations against Enterobacteriaceae moderately susceptible or resistant to this new cephalosporin.

The interaction of cefotiam with each of the four aminoglycosides gentamicin, tobramycin, netilmicin and amikacin were studied by the broth microdilution method ("checkerboard" technique) against 36 strains of Enterobacteriaceae chosen for their moderate susceptibility (MIC: 4-32 mg/l) or resistance (MIC: 64-512 mg/l) to cefotiam. A high rate of synergistic combinations was found with all the aminoglycosides: 81% with gentamicin, 76% with amikacin, 67% with tobramycin and netilmicin. The therapeutic value of these interactions appeared excellent.

Amikacin↗
PubMed1986

Aminoglycosides and renal acid excretion.

The effect of three aminoglycosides, gentamicin, netilmicin and amikacin, on renal acid excretion was studied in rats treated with doses equivalent to 10 times those used clinically. The gentamicin and amikacin groups showed a marked decrease (P less than 0.05), in glomerular filtration rate (GFR), U/P inulin ratio and renal plasma flow (RPF), while in the normal acid-base state. Under acidotic conditions, only gentamicin promoted significant alterations in GFR and RPF. Net acid excretion as measured by the acid balance (BH) was calculated as the sum of ammonium excretion (NH4+) and titratable acidity (AT) minus the amount of excreted bicarbonate (CHCO3-). Under normal conditions, netilmicin promoted a considerable fall in both NH4+ and AT, which led to a significant decrease in BH, whereas no changes were observed in these parameters with the other two drugs. In contrast, during acute metabolic acidosis, all tested antibiotics promoted a marked fall in BH, particularly due to a significant decrease in NH4+ and AT. These data suggest that the effects of aminoglycoside treatment during acute metabolic acidosis in clinical practice deserve further study in view of possible deleterious effects on the clinical state.

Acidosis, Renal Tubular↗