netilmicin and arbekacin

Following the development of amikacin, pharmaceutical companies made intensive efforts to find even more potent and broader-spectrum aminoglycosides. This effort was justifiable in view of the fact that over the preceding decade, these agents, because of their unique properties, had proven to be the primary weapons in the therapeutic armamentarium for the treatment of seriously ill patients. Since the toxicities associated with the aminoglycosides were beginning to limit their use in general medicine, researchers ultimately shifted their emphasis from probing for higher-potency, broader-spectrum agents to finding those with a reduced potential for toxicity. This article addresses the issue of whether superior aminoglycoside derivatives will reach the marketplace in the future. A comparison is made of several key properties of virtually all aminoglycosides that have reached an advanced preclinical development stage, gone into the clinic, or been registered for commercial use over the past 10 years. The following parameters are used for comparisons with already marketed aminoglycosides: antibacterial potency, as measured by relative minimum inhibitory concentrations for 50 percent of the strains tested, against wild-type Pseudomonas aeruginosa; degree of resistance to inactivation by microbial enzymes; and potential for toxicity utilizing comparative acute intravenous lethal doses for 50 percent of the population in mice, values that appear to predict the maximum recommended daily doses in man. An assessment of a number of compounds, including three structurally related to gentamicin, two to sisomicin, two to kanamycin A, three to kanamycin B, and two to fortimicin, revealed that none had overall properties superior to those already being utilized commercially. In no case did a compound prove to be less toxic, and in many instances, the antibacterial potency of the newer agents was lower than that exhibited by the older aminoglycosides. Some increase in resistance to inactivating enzymes was seen, but only BB-K 311 proved refractory to more enzymes than did amikacin. In view of this and the fact that no new agents of promise have moved into the development stage during the past five years, it seems safe to say that the current armamentarium of aminoglycosides is all that will be available for use in the foreseeable future.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Microbial; Gentamicins; Humans; Kanamycin; Lethal Dose 50; Mice; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Sisomicin; Tobramycin

Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153 amino acids and has 86.3% identity to AAC(6')-Iz. Escherichia coli transformed with a plasmid containing aac(6')-Iak exhibited decreased susceptibility to arbekacin, dibekacin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography showed that AAC(6')-Iak acetylated amikacin, arbekacin, dibekacin, isepamicin, kanamycin, neomycin, netilmicin, sisomicin, and tobramycin but not apramycin, gentamicin, or lividomycin.

Topics: Acetyltransferases; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Neomycin; Netilmicin; Sisomicin; Stenotrophomonas maltophilia; Tobramycin

Among methicillin resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens during 5 years period from 1998 through 2002 in Cancer Institute Hospital, Japanese Foundation for Cancer Research, a total of 100 strains, one per patient, were successively selected each year, and their sensitivity to various antibacterial agents was measured to assess changes over five years in their sensitivity to these drugs. The following results were obtained. 1. Little or no change was observed in the sensitivity to arbekacin during 5 years period. In contrast, a tendency toward decreased sensitivity was observed with vancomycin and teicoplanin, with the tendency more marked with the latter agent. 2. Arbekacin, vancomycin and teicoplanin inhibited the growth of all clinical isolates in the year 2002 at 3.13, 1.56 and 12.5 microg/mL, respectively. 3. The sensitivity to netilmicin tended to decrease over the years. 4. Minocycline, imipenem and ofloxacin had little or no antibacterial activity, with MIC50 of more than 12.5 microg/mL throughout the years studied. 5. Ninety five percent of MRSA strains isolated during the five years were classified as coagulase type II, and enterotoxins were found to be type C in 51% and type AC in 17% of the strains studied.

Topics: Aminoglycosides; Coagulase; Dibekacin; Drug Resistance, Bacterial; Enterotoxins; Humans; Imipenem; Methicillin Resistance; Netilmicin; Ofloxacin; Staphylococcus aureus; Teicoplanin; Vancomycin

Aminoglycoside antibiotics are known to produce a depression of neuromuscular function which may cause prolonged paralysis of respiratory muscles. However, differences in the effects of aminoglycoside antibiotics on diaphragm and limb muscles have not been investigated. We determined the neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate, isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and soleus muscles in anesthetized rabbit nerve-muscle preparations. Neuromuscular block was assessed by mechanical response with single twitch stimulation. Cumulative drug dose-response curves were obtained for three different muscles in 24 rabbits. The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis anterior and soleus muscles were calculated. The neuromuscular blocking effects of all the aminoglycosides on ED(50) and ED(95) values were in the order of soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis anterior, respectively. The ED(50) ratios for the tibialis anterior and soleus muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Diaphragm; Dibekacin; Dose-Response Relationship, Drug; Gentamicins; In Vitro Techniques; Male; Muscle Contraction; Muscle, Skeletal; Netilmicin; Neuromuscular Junction; Rabbits

The neuromuscular blocking properties of aminoglycoside group of antibiotics arbekacin sulfate (ABK), astromicin sulfate (ASTM), isepamicin sulfate (ISP), netilmicin sulfate (NTL) and d-tubocurarine were studied in 30 rabbits anesthetized with pentobarbital. The left gastrocnemius tendon was cut and secured to a force-displacement transducer. The left tibial nerve was directly stimulated by electrodes with supramaximal square waves of 0.1 msec duration at a frequency of 0.1 Hz. The resultant force of twitch tension was recorded. The intravenous administration of ABK 60-100 mg/kg, ASTM 160-320 mg/kg, ISP 320-480 mg/kg or NTL 20-40 mg/kg resulted in dose-dependent decreases in twitch tensions. The ED50 values of 4 antibiotics were NTL = 30.2 mg/kg (4.2 x 10(-2) mmol/kg) < ABK = 78.3 mg/kg (1.4 x 10(-1) mmol/kg) < ASTM = 215.2 mg/kg (3.6 x 10(-1) mmol/kg) < ISP = 359.7 mg/kg (6.3 x 10(-1) mmol/kg), respectively. These antibiotics-induced blockades were antagonized by calcium or by neostigmine. Although the relative neuromuscular blocking potencies of 4 antibiotics equipotent to d-tubocurarine on the basis of therapeutic doses in man were below 0.6 mg, it may be concluded that the potential clinical hazard lies in the sequence of administration of the aminoglycoside group of antibiotics.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Dose-Response Relationship, Drug; Gentamicins; Netilmicin; Neuromuscular Blocking Agents; Rabbits; Tubocurarine

The bactericidal activities of arbekacin (ABK), vancomycin (VCM), gentamicin (GM) and netilmicin (NTL) in mixed culture with Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were examined using an in vitro computer programmed pharmacokinetic simulation system and also the protective effect of these agents on systemic infection in neutropenic mice was examined. In a mixed culture of S. aureus No. 235 (MRSA) and P. aeruginosa E7, ABK showed a strong bactericidal activity and an inhibition of regrowth against both bacteria, and GM and NTL showed similar effects. On the other hand, VCM showed a bactericidal activity against S. aureus No. 235, but not against P. aeruginosa. In the protective study, ABK was evidently more effective than GM, NTL or VCM against a systemic mixed infection of mice with S. aureus No. 235 and P. aeruginosa E7. In brief, the ED50 values of ABK, VCM, GM and NTL were 19.5, > 100, 40.5 and 45.2 mg/kg, respectively.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Computer Simulation; Dibekacin; Gentamicins; Male; Methicillin Resistance; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

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)

Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Female; Gentamicins; Kanamycin; Kidney Cortex; Kidney Diseases; Netilmicin; Rats; Rats, Inbred Strains

The activity of 5 aminoglycosides compounds (habekacin, amikacin, gentamicin, netilmicin and tobramycin) was studied by an agar dilution method, against 235 strains of Enterobacteriaceae and 146 other Gram negative bacilli. 79 to 98% of susceptible strains were observed, according to the aminoglycoside compound. Habekacin and amikacin were the most effective, specially against the more frequently resistant bacteria: Enterobacter, Serratia, Hafnia, Acinetobacter, Pseudomonas aeruginosa. In comparison with a previous study, no evolution was observed in the resistance to aminoglycosides.

Topics: Acinetobacter; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Microbial; Enterobacteriaceae; Gentamicins; Kanamycin; Microbial Sensitivity Tests; Netilmicin; Pseudomonas aeruginosa; Tobramycin