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Netilmicin kinetics in urology.

Plasma kinetics of netilmicin, an aminoglycoside antibiotic was studied in 62 patients undergoing urologic surgery. Despite the use of a standard 100 mg-dose, no toxic levels were achieved except in one patient. A poor correlation was found between netilmicin plasma elimination constant and creatinine clearance (r = 0.34, p = NS). We can conclude that the prediction of netilmicin plasma concentrations is not possible using only demographic patient's data. The monitoring of netilmicin levels should be performed in long-term treatments but not in 4-dose regimes such as in urologic prophylaxis.

Adult↗

Renal tolerability of four different once-daily dose regimen of netilmicin in critical care patients.

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.

Acute Kidney Injury↗

[Pefloxacin + metronidazole versus netilmicin + metronidazole in the prevention of nosocomial infections in contaminated surgery. Pefloxacin Study Group].

Pefloxacin plus metronidazole versus netilmicin plus metronidazole in the prevention of nosocomial infections during contaminated surgery. Surgical prophylaxis is widely used in contaminated surgery, especially colorectal surgery. In this clinical trial the efficacy of pefloxacin 800 mg i.v. slow infusion associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then metronidazole alone after 6 and 12 hours versus netilmicin 200 mg i.m. associated to metronidazole 500 mg i.v. 1-2 hours before surgery and then both after 6 and 12 hours were evaluated in 97 patients suffering by colorectal surgery. Efficacy of prophylaxis in patients was evaluated in terms of appearance of post-surgical infections (abdominal, urinary, respiratory and wound infections). In pefloxacin + metronidazole group (53 patients), two cases of wound infections (3.8%) and three cases of respiratory infections (5.8%) were observed. In netilmicin + metronidazole group (44 patients), two cases of wound infections (4.9%), three cases of urinary infections (7%), three cases of respiratory infections (7.5%) and one case of intra-abdominal infection were observed. Our data confirmed that in colorectal surgery, the association pefloxacin, drug with microbiological and pharmacokinetics characteristics suitable for prophylaxis + metronidazole, active against anaerobes pathogens, prevents post-surgical infections as well as a reference association (netilmicin + metronidazole), with the advantage of a single administration.

Adolescent↗

[Cefixime versus amoxicillin plus netilmicin in the treatment of community-acquired non-complicated acute pyelonephritis].

BACKGROUND: Community-acquired non-complicated acute pyelonephritis (APN) is a frequent, occasionally serious infection (around 20% of the cases are bacteremic) that usually requires hospital admission. The third generation oral cephalosporins which are active against more than 95% of E. coli strains should allow the outpatient management of these patients. OBJECTIVE: To evaluate the bacteriological and clinical efficacy of oral cefixime in comparison to amoxicilin plus netilcilin in the treatment of APN. PATIENTS AND METHODS: Patients older than 18 years affected by APN were included in a fourteen month prospective study. According to a random numbers chart, the patients received cefixime (400 mg/24 h in a single daily dose for 12 days) or amoxicilin (1 g/8 h per os) plus netilmicin (4 mg/kg/24 h in a single intramuscular daily dose) during five days followed by 7 days of an oral treatment chosen according to the susceptibility pattern of isolated microorganism. RESULTS: Sixty-one patients received cefixime and 65 amoxicillin plus retilmicin. There were no significant differences between both groups of patients. Thirty-two patients presented bacteremia (25.4%). The mean (SD) eak and trough concentrations of netilmicin were 11.4 (2.8) mg/l and 0.38 (0.4) mg/l, respectively. Clinical response was favorable in 97% of patients treated with cefixime and in 98% of those treated with amoxicilin plus netilmicin (p = NS). The infection recurred in 10 out of 59 patients (16.9%) in the cefixime arm of the study and in 9 out of 64 patients (14%) treated with amoxicillin plus netilmicin (p = NS). Tolerance to the study drugs was good in both arms of the study, and renal function remained normal. CONCLUSION: Cefixime seems to be an acceptable alternative to the regimens containing an aminopenicillin and an aminoglycoside for the treatment of community-acquired non-complicated APN.

Acute Disease↗

Antimicrobial activity in vitro of netilmicin and comparison with sisomicin, gentamicin, and tobramycin.

The antimicrobial activity of netilmicin, a new semisynthetic aminoglycosidic aminocyclitol, was determined against 123 recent gram-negative clinical isolates susceptible to gentamicin and 60 isolates resistant to either sisomicin, gentamicin, or tobramycin. The minimal inhibitory concentrations and minimal bactericidal concentrations of netilmicin, sisomicin, gentamicin, and tobramycin against Pseudomonas, Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, and indole-positive Proteus were, in general, quite similar. Gentamicin was the most active against Serratia. A total of 54, 67, and 88% of gentamicin-resistant Pseudomonas, Serratia, and Klebsiella, respectively, were susceptible to netilmicin. Strains of indole-positive Proteus, Acinetobacter, Providencia, and E. coli resistant to gentamicin were likely to be resistant also to netilmicin.

Aminoglycosides↗

In vitro studies with netilmicin compared with amikacin, gentamicin, and tobramycin.

Netilmicin, a new semisynthetic aminoglycoside derived by ethylation of the 1-N position of the deoxystreptamine ring of sisomicin, was tested in vitro with 4,070 strains of gram-negative bacilli isolated at the UCLA Medical Center during 1975 to 1976, using the agar dilution technique and an inoculum of approximately 10(4) organisms. Results were compared with those simultaneously obtained for amikacin, gentamicin, and tobramycin. Using Mueller-Hinton medium, inhibitory concentrations in broth correlated with those obtained by the agar dilution method except for Pseudomonas aeruginosa, where a 2- to 16-fold difference in susceptibility was noted. For most clinically significant Enterobacteriaceae and P. aeruginosa, the activity of netilmicin in vitro was comparable or superior to that of gentamicin, tobramycin, and amikacin with respect to potency by weight and achievable blood levels. Against gentamicin-resistant strains (MIC > 16 mug/ml), the activity of netilmicin paralleled that of amikacin with the exception of Providencia stuartii, which was inhibited by amikacin but not by netilmicin.

Amikacin↗

In vitro activity of netilmicin compared with gentamicin, tobramycin, amikacin, and kanamycin.

The in vitro activity of netilmicin was compared with that of gentamicin, tobramycin, amikacin, and kanamycin against 636 strains of bacteria recently isolated from clinical sources. Gentamicin was the most active antibiotic, but netilmicin and tobramycin closely paralleled it. Netilmicin was generally four-to eightfold less active than gentamicin against Serratia and group A streptococci, and was twofold less active against Pseudomonas aeruginosa. When effects of inoculum size and concentration of divalent cations in the media were evaluated, netilmicin was shown to be similar to gentamicin in vitro. Minimum inhibitory concentrations for P. aeruginosa were increased as much as 18-fold when the Mg(2+) and Ca(2+) concentrations were increased to physiological levels in Mueller-Hinton broth.

Amikacin↗

In vitro studies on netilmicin, a new aminoglycoside antibiotic.

Netilmicin, a semisynthetic derivative of sisomicin, was tested in vitro against 600 clinical bacterial isolates. At a concentration of 1.56 mug/ml, over 90% of gram-negative bacilli were inhibited. Netilmicin was substantially more active against isolates of Serratia marcescens and Enterobacter spp. than gentamicin, sisomicin, tobramycin, or amikacin. Isolates of Staphylococcus aureus (both penicillin G susceptible and resistant) were quite susceptible to netilmicin. Most isolates of Klebsiella spp. and Serratia spp. and some of the isolates of Pseudomonas aeruginosa that were resistant to gentamicin proved to be susceptible to netilmicin.

Anti-Bacterial Agents↗

Clinical and bacteriological evaluation of netilmicin in gram-negative infections.

A preliminary study was conducted with netilmicin, a new aminoglycoside antibiotic. Its effectiveness was evaluated in vitro against 546 strains of Enterobacteriaceae and Pseudomonas aeruginosa isolated from clinical material. Its effectiveness against gentamicin-susceptible strains was roughly similar to that of gentamicin and other newer aminoglycoside antibiotics. Cross-resistance to netilmicin was found in 9 of 44 gentamicin-resistant strains. A favorable clinical response was observed in 70% of the patients treated with a dose of netilmicin ranging from 4.5 to 7.5 mg/kg. However, the appearance of granular casts was seen in 7 of 10 patients receiving the higher dosage of netilmicin (7.5 mg/kg) and a rise in blood urea nitrogen or serum creatinine levels was observed in 5 of these patients.

Bacteria↗

High-pressure liquid chromatographic assay of netilmicin in plasma.

A high-pressure liquid chromatographic method for the quantitative determination of netilmicin in plasma was developed. The procedures involve acetonitrile protein precipitation, methylene chloride extraction, and dansylation to form the fluorescent dansyl derivative of netilmicin, which is extracted into ethyl acetate and chromatographed on a reverse-phase column with aqueous acetonitrile as the mobile phase. A good linear relationship between peak height measurements and netilmicin concentrations was found. This method is sensitive and reproducible; a netilmicin concentration as low as 0.5 mug/ml can be measured with only 0.1 ml of plasma sample. The results of assays of plasma or serum samples by this high-pressure liquid chromatographic method correlate well with those obtained by microbiological assays.

Chromatography, High Pressure Liquid↗

In vitro activity of sisomicin and netilmicin alone and in combination with nafcillin, oxacillin and methicillin against enterococci.

The in vitro activity of sisomicin and netilmicin alone and in combination with nafcillin, oxacillin and methicillin against 30 strains of enterococci was investigated. Sisomicin and netilmicin alone were not very effective against enterococci. There was enhanced killing of some strains of enterococci by the combination of sisomicin or netilmicin with one of the three penicillinase-resistant penicillins. Nafcillin was the most effective penicillinase-resistant penicillin in the combination. Sisomicin appeared to be slightly more effective than netilmicin in combination with one of the penicillinase-resistant penicillins against enterococci.

Drug Synergism↗

Prediction of netilmicin disposition in neonates.

Multiple regression analyses of data from 33 neonates who received netilmicin therapy showed that concurrent treatment with other drugs (Drg), creatinine clearance (CLcr), gestational age (GA), and an apgar score of less than 6 at 1 min (Agl') were significant determinants of netilmicin clearance. Apparent volume of distribution was significantly affected by postnatal age (PNA), gender, the presence of ascites and/or oedema (A/O), and whether or not the neonate was small for gestational age (SGA). The following formulae were obtained: [formula: see text] The regression formulae were shown to predict netilmicin plasma concentrations with good precision and a non-significant bias in a further 15 neonates studied prospectively.

Apgar Score↗

Comparative oto-vestibular effects in the pigmented guinea pig after dibekacin and netilmicin treatment.

We treated groups of pigmented guinea pigs with either intramuscular netilmicin or dibekacin at 100 and 150 mg/kg per day for 3 weeks. Saline was used as the control solution. All animals were tested weekly for both vestibular and auditory functions. The vestibular function was evaluated by the duration of post-rotatory nystagmus (PRN) elicited by interrupting the rotation of the animal around the vertical axis; auditory function was evaluated by the threshold response for the Preyer's pinna reflex (PPR). All animals were then sacrificed and either their labyrinths or Corti organs were processed for further investigations using the scanning electron microscope (SEM). The duration of PRN decreased over the treatment period in all of the groups as a result of adaptation. However, 150 mg/kg dibekacin produced a significant decrease of the PRN responses as compared to the control and other groups. This effect also continued during the recovery period. Likewise, the PPR threshold of the animals receiving 150 mg/kg dibekacin showed a significant increase at the end of the treatments and during the recovery period, while the other dibekacin group had no significant auditory impairment. Netilmicin at both doses did not significantly affect responses following either vestibular or auditory stimulations. SEM observations demonstrated that the sensory epithelia of the labyrinths and Corti organs affected by 150 mg/kg dibekacin had great losses of stereocilia, while comparable doses of netilmicin (150 mg/kg) had only very moderate losses of stereocilia in the labyrinths but not in the Corti organs.

Animals↗

Intrathecal administration of netilmicin in gentamicin-resistant ventriculitis.

In ventriculitis caused by Gentamicin-resistant staphylococcus aureus and staphylococcus epidermidis, Netilmicin was administered intrathecally to 19 patients under continuous control of the Netilmicin concentration in cerebro-spinal fluid (CSF). This therapy was able to bring these otherwise lethal infections under control, usually within 10 days. Pharmacokinetic studies with different doses have shown that doses of 2 X 3 mg are to be recommended in moderately severe cases of ventriculitis, and in most severe infections 3 X 3 mg daily intraventricularly for adults. In infants daily intraventricular injections of 2 X 0.4-0.5 mg Netilmicin are a sufficient dose to produce an effective antibiotic concentration level.

Adolescent↗

Inactivation of netilmicin by carbenicillin.

Netilmicin was added to human serum and stored at various temperatures and carbenicillin concentrations prior to bioassay. Inactivation of netilmicin increased with temperature and carbenicillin concentration. The order of inactivation of aminoglycosides was: tobramycin greater than gentamicin, netilmicin greater than amikacin.

Amikacin↗

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients.

We assessed the efficacy of a piperacillin (3 x 4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.

Acute Disease↗

Once daily dosing of netilmicin in neonatal and pediatric intensive care.

OBJECTIVE: To examine a once daily dosing regimen of netilmicin in critically ill neonates and children. DESIGN AND SETTING: Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit. For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h. The dose ranged from 3.5-6 mg/kg, mainly depending upon gestational and postnatal age. Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing. RESULTS: All peak levels (n = 28) were clearly above 12 mumol/l (mean 22, range 13-41 mumol/l). Eighty-nine trough levels were within desired limits (< 4 mumol/l) and 11 (11%) above 4 mumol/l, mostly in conjunction with impaired renal function. CONCLUSIONS: Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function.

Critical Illness↗

Treatment of LD100 Escherichia coli septic shock with netilmicin and methylprednisolone in baboons.

Treatment efficacy with netilmicin sulphate/methylprednisolone sodium succinate in a severe septic shock baboon model, using an LD100 of live Escherichia coli, was evaluated. All the animals treated with both netilmicin and methylprednisolone were permanent (greater than or equal to 7 days) survivors, whereas none of the untreated baboons lived more than 24 hours. These results indicate that, in a baboon model, netilmicin is an effective alternative to gentamicin (with methylprednisolone) in the treatment of severe septic shock.

Animals↗