netilmicin and Acute-Kidney-Injury

The antibiotics of the aminoglycoside group are all potentially nephrotoxic. Aminoglycosides are exclusively excreted via the kidneys by glomerular filtration. On passing the proximal tubular cells of the nephron, an active reabsorption and intracellular concentration, 10-20 times the serum concentration, take place. Aminoglycosides are trapped in the lysozymes and inhibit cell metabolism. Functional changes are at first discrete, comprising polyuria, slight proteinuria, enzymuria and glycosuria. With more progressive changes the glomerular filtration rate decreases, followed by increased blood urea and serum-creatinine. The urine contains protein, casts and shedded tubular cells. Ultimately, but rarely, oligo-anuric renal failure may be encountered. Compared with gentamicin, the newer aminoglycosides, amikacin, tobramycin and netilmicin show in animal experiments a decreasing nephrotoxicity in the mentioned order. Extensive studies have demonstrated that netilmicin may be the drug with the least nephrotoxic potential. Clinical studies confirm that netilmicin is less nephrotoxic than gentamicin and compares favourably with tobramycin and amikacin. A survey of the literature is given.

Topics: Acute Kidney Injury; Aminoglycosides; Animals; Dose-Response Relationship, Drug; Gentamicins; Glomerular Filtration Rate; Humans; Kidney; Kidney Glomerulus; Kidney Tubules; Netilmicin; Tobramycin

A prospective, randomized trial was conducted in a medical intensive care unit to assess safety and tolerability of four different dose regimens of intravenous netilmicin given once daily in the treatment of febrile episodes in critically ill patients. Eighty patients with febrile episodes during their stay in the intensive care unit were included in the study. The patients were randomized into four groups: Group 1 received a single daily dose of netilmicin based upon weight, age and renal function according to a dosage nomogram [13] (mean dose 298 +/- 29 mg, median 300 mg, range 250-350 mg), group 2 received 150% of this standard dose (mean 418 +/- 45 mg, median 400 mg, range 350-500 mg), group 3 200% (mean 525 +/- 41 mg, median 500 mg, range 400-550 mg) and group 4 250% (mean 710 +/- 39 mg, median 650 mg, range 600-750 mg). Duration of treatment was six days. Positive cultures were obtained in 29 patients. Serum creatinine and creatinine clearance, as well as netilmicin trough levels and levels of alpha 1-microglobulin showed no significant difference between the groups before, during, and after therapy. Our results indicate that with once daily dosing even high doses of netilmicin are well tolerated in patients with a creatinine clearance of > 70 ml/min before therapy. Necessary precautions include monitoring of drug trough levels (< 1 mg/L) and maintenance of adequate volume status.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Intensive Care Units; Kidney Function Tests; Male; Middle Aged; Netilmicin; Prospective Studies

In two prospective, randomized studies conducted in West Germany and involving 80 patients, netilmicin-ticarcillin was compared to tobramycin-ticarcillin in the treatment of serious systemic infections. Both regimens were essentially identical with respect to the clinical and bacteriological results they produced. The netilmicin group developed significantly less nephrotoxicity than the tobramycin group (0% versus 15%, P = 0.03). Ototoxicity also occurred less frequently in the netilmicin-treated patients (3% versus 10%, P = 0.4). In a large collaborative study involving 15 centres, 254 patients were enrolled. Clinical and bacteriological responses were excellent, with netilmicin and tobramycin equally effective, but the incidences of nephrotoxicity and ototoxicity were lower in patients treated with netilmicin than those receiving tobramycin.

Topics: Acute Kidney Injury; Aged; Bacterial Infections; Clinical Trials as Topic; Ear Diseases; Female; Gentamicins; Gram-Negative Bacteria; Humans; Male; Netilmicin; Random Allocation; Tobramycin

Topics: Acute Kidney Injury; Animals; Diltiazem; Humans; Netilmicin; Rabbits

88 patients (aged 55-96 years) with severe infections were treated during ten days with one of four different aminoglycosides: gentamicin, dibekacin, netilmicin (3 mg/kg/day) or amikacin (15 mg/kg/day). Creatinine clearance and urinary N-acetyl-glucosaminidase (NAG) activity were measured daily. In addition, NAG isoenzyme patterns were determined on the day of maximal urinary NAG excretion. Aminoglycoside-induced acute renal failure was more prevalent in the gentamicin group (42.8%) than in the dibekacin, netilmicin or amikacin groups (42.8%, 5.5% and 0% respectively). No relationship was found between total urinary NAG activity and nephrotoxic risk. Conversely, significantly elevated levels (p less than 0.001) of B isoenzyme were detected in the gentamicin group, whereas the highest A and I isoenzyme levels were found in the dibekacin and netilmicin groups. These results suggest that functional enzymuria with preferential urinary excretion of A and I isoenzymes should be distinguished from lesional enzymuria with preferential urinary excretion of the B isoenzyme. According to our data, the NAG-B isoenzyme may possibly be a specific marker of aminoglycoside nephrotoxicity.

Topics: Acetylglucosaminidase; Acute Kidney Injury; Aged; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Female; Gentamicins; Hexosaminidases; Humans; Isoenzymes; Male; Middle Aged; Netilmicin