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PubMed2003

Evaluation of a netilmicin-loading dose in very low birthweight infants.

BACKGROUND: The bactericidal efficacy of aminoglycosides is directly related to maximum serum concentrations, particularly the initial one. Therefore, several groups have recommended an aminoglycoside loading dose. Our goal was to develop a simplified dosage regimen for preterm infants which would result in therapeutic maximum serum concentrations early in the course of therapy. METHODS: Open, noncomparative study during November 2000 to April 2001. The modified netilmicin-dosing protocol included a loading dose of 5 mg/kg in the first week of life, followed by a maintenance regimen of 3.5 mg/kg every 24 h. After the first week of life the corresponding doses were 6 (loading) and 5 mg/kg (maintenance). A peak level was measured 30 min after the second dose, and a trough level immediately before the third dose. RESULTS: Thirty-five very low birthweight infants (mean birthweight 876 +/- 170, range 536-1,385 g; mean gestational age 26 +/- 1.8, range 23-30 weeks) who had 46 episodes of netilmicin treatment were included in the analysis. Mean netilmicin peak and trough values were 15.9 +/- 3.7 (range 8.9-28.9) and 3.4 +/- 1.3 (range 1.0-7.8) micromol/l, respectively. Ninety-one percent of all peak levels were within the targeted range of > or =10 micromol/l. Eleven trough values (24%) were > or =4 micromol/l: in 7 instances netilmicin was administered within the first week of life, 5 of these patients had concomitant indomethacin treatment. Only 1 of the 35 neonates had a rise in serum creatinine of > or =0.5 mg/dl during netilmicin therapy. Hearing evaluations were performed in 25 of the 29 surviving infants at discharge home, all of which gave normal results. CONCLUSIONS: The new netilmicin-dosing protocol yielded therapeutic maximum serum concentrations in 91% of cases after the second dose. However, a significant number of very low birthweight infants had elevated trough levels, particularly when netilmicin was administered in the first week of life with concomitant indomethacin treatment. We speculate that a longer interval between the loading dose and the first maintenance dose would result in fewer elevated trough levels with a similarly high number of therapeutic peak levels.

Anti-Bacterial Agents↗
PubMed1979

Netilmicin: clinical evaluation of efficacy and toxicity of a new aminoglycoside.

The efficacy and toxicity of netilmicin, a new semisynthetic aminoglycoside, was clinically evaluated in fifty-two patients with moderate to severe infections with Gram-negative rods or Staph. aureus. Average duration of treatment was 14 days and mean total dose 2,960 mg. One-hour mean value of netilmicin serum concentration was 6.4 microgram/ml and mean trough value 1.2 microgram/ml. Forty-four patients were cured or improved. In twenty-one of them the effect could be attributed to netilmicin alone; the other twenty-three had a combined therapy. No improvement took place in five, but four of them could not be regarded as netilmicin failure. One patient with Pseudomonas aeruginosa infection was possible failure. The sensitivity of the causative bacteria to netilmicin was studied and compared with amikacin, gentamicin, sisomicin and tobramycin. Vestibular function and hearing acuity was thoroughly examined by electronystagmography and audiography. Drug-related VIIIth nerve damage could not be confirmed in any of our patients. Five patients showed a rise of serum creatinine of 30 mumol/l. This shows that netilmicin, similar to other aminoglycosides, is a potential nephrotoxic drug. Netilmicin appears to be an efficacious aminoglycoside and the oto- and nephrotoxicity is low, if careful attention is paid to the renal function and the serum concentrations of the drug.

Adolescent↗
PubMed2002

Netilmicin effect on urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) in preterm newborns with and without anoxia.

The study aim was to evaluate urinary excretion of Retinol Binding Protein (RBP), compared with urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), in preterm infants with anoxia and netilmicin treatment. Urinary RBP and NAG were evaluated in 83 preterm newborns divided in 4 groups: 37 healthy preterm newborns (controls); 14 with neonatal anoxia; 16 treated with ampicillin + netilmicin; 16 with neonatal anoxia and treated with ampicillin + netilmicin. RBP was determined by an automated nephelometric technique and NAG by a colorimetric method on 5-h urine samples in the first week of life. Results showed that urinary excretion of RBP (average from first week values) was 1.06+/-0.67 g/mol creatinine (mean +/- SD) in controls, 1.99+/-1.41 in antibiotic-treated newborns, 3.99+/-4.57 in anoxic newborns and 3.75+/-3.48 in anoxic newborns under antibiotic treatment. When gestational age was not considered, a marked effect of anoxia (P<0.001) and a borderline effect of netilmicin (P<0.059) on RBP excretion were detected by ANOVA. However when gestational age was also considered by analysis of covariance, it appeared as the strongest predictor of RBP excretion (P<0.001), while the effect of netilmicin was no longer significant (P=0.181). The effect of anoxia persisted, although less remarkable (P=0.010). Conversely anoxia did not affect urinary NAG excretion, which was rather correlated with gestational age and netilmicin administration. The authors conclude that RBP and NAG urinary excretion may be used to discriminate between neonatal anoxia and netilmicin treatment, respectively as etiologic factors of renal tubular damage in the newborn.

Acetylglucosaminidase↗
PubMed1989

Netilmicin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Netilmicin is a semisynthetic aminoglycoside derived from sisomicin. It is active against most Gram-negative and some Gram-positive bacteria, including many gentamicin-resistant strains. Netilmicin has proved to be effective in Gram-negative infections of the urinary tract, skin and skin structure, and lower respiratory tract, as well as in intra-abdominal infections, septicaemia and other miscellaneous infections. In some trials, the more easily implemented once daily administration of netilmicin has been as effective as multiple dosing regimens. However, further investigation is required to confirm that efficacy and safety are not compromised with once daily administration. Comparative studies have generally revealed similar clinical and bacteriological efficacies between netilmicin and gentamicin, amikacin or tobramycin. As with other aminoglycosides, the principal adverse effects of netilmicin are nephrotoxicity and ototoxicity. Although animal studies strongly suggest that these are less common with netilmicin than with related drugs, there appears to be no difference in their incidence in clinical use; in clinical trials the incidence of nephrotoxicity and ototoxicity has been low, with the symptoms in many cases being minor and reversible. Netilmicin is, therefore, an effective antibacterial drug for the parenteral treatment of severe infections, offering theoretical advantages in safety which may indicate its use for patients believed to be at risk of adverse effects.

Animals↗
PubMed1978

Therapeutic experience with netilmicin.

Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.

Adolescent↗
PubMed1999

[A series of clinical study on netilmicin].

OBJECTIVE: To evaluate the clinical effects, pharmacokinetics, post-antibiotic effect (PAE) and toxicity of netilmicin as a single daily dose in the treatment of lower respiratory tract infection. METHODS: 48 cases were divided into 3 groups: In the first group, Netilmicin(6 mg.kg-1.d-1) was administered in a single daily dose; in the second group, netilmicin (200 mg/d) was combined with cefazolin (3 g, Q12 h); and in the third control group, the combination of cefazolin and Amikacin was used. Pharmacokinetics were studied in 7 patients using the TDX system, and PAE induced by Netilmicin was determined by the Avantage microbiologic system. Clinical symptoms, laboratory studies, chest X-rays, and side effects were observed. RESULTS: The overall clinical effects of the first group were better than those of the third group. The mean serum concentration of netilmicin was 27.23 mg/L, the valley serum concentration was 0.23 mg/L, T1/2 beta was 5.059 h, AUC was 70 micrograms.h-1.ml-1.netilmicin at concentrations 0.5, 1.0 and 4 times the MIC showed different degrees of PAE against 4 strains of bacterium. Nephrotoxicity and ototoxicity were not found in the treatment group. CONCLUSIONS: Netilmicin in a single daily dose resulted in a high peak serum concentration and big AUC. As a concentration-dependent bactericidal agent, netilmicin showed a longer PAE and better therapeutic effects.

Amikacin↗
PubMedDate not supplied

[Pharmacokinetics of netilmicin in neonates].

UNLABELLED: Our goal was to perform a pharmacokinetic analysis of netilmicin to develop the optimum dosage regimen of this antibiotic in premature neonates hospitalized in Neonate Intensive Care Unit of the Institute of Mother and Child in Warsaw. MATERIALS AND METHODS: The pharmacokinetics of netilmicin was studied in 80 neonates, divided for analysis into three groups according to gestational age: group I - 10 full-term neonates (b.w. 3225 +/-502 g); group II - 35 premature neonates between 29-32 weeks (b.w. 1134+/-311 g); and group III - 35 premature neonates between 23-28 weeks (b.w. 910 +/-243 g). The whole studied group of neonates was initially given i.v. netilmicin every 24 h, then the dosing interval for the safety reasons was prolonged to 48 h in the premature group. The neonates received netilmicin in the following doses: group I - mean dose 6.2 +/-0.42 mg/kg; group II - 5.911+/-0.529 mg/kg and group III - 6.014+/-0.313 mg/kg. Serum netilmicin concentrations were determined by fluorescence polarization immunoassay (FPIA) - TD(x)FL(x) (Abbott). RESULTS: The mean of pharmacokinetic parameters for groups I, II, and III were defined respectively: t(0.5) (h): 7.14+/-1.88, 12.68+/-4.26, 15.98+/-5.9; AUC0-( (microg x h/ml): 149+/-41, 303+/-100, 401+/-172; Cl/kg (l/h/kg): 0.748+/-0.24, 0.371+/-0.13, 0.289+/-0.1; MRT0-( (h): 6.3+/-2.8, 10.8+/-6.3, 15.5+/-9.3; V(dss) (l/kg): 0.75+/-0.24, 0.59+/-0.52, 0.44+/-0.19. The obtained mean netilmicin serum concentrations (microg/ml) were: once-a-day dosage: C(max) - 10.25+/-2.616 (group I), 12.2+/-2.65 (group II), 12.9+/-2.77 (group III); C(min) - 1.158+/-0.657 (group I), - 2.65+/-1.02 (group II), 3.23+/-1.42 (group III); once-a-48 h dosage: C(max) - 11.7+/-1.09 (group II), 13.9+/-6.53 (group III); C(min) - 1.09+/-0.64 (group II), 1.74+/-0.98 (group III). CONCLUSIONS: 1. All the calculated pharmacokinetic parameters in the premature neonate groups (group II and III) significantly differs from the parameters calculated for full-term neonates. 2. Significant correlations were obtained between birth weight, gestational age and all the calculated pharmacokinetic parameters in all the groups of neonates. 3. The obtained results indicated that the use of the dosing schedule of netilmicin with the dose intervals of 48 h in premature neonates should guarantee adequate peak and trough levels without the need of routine monitoring of each patient in the premature neonate group except the very low weight neonates. Detection of the specific sensitivity of lymphocytes T during the diagnosis of food allergy.

Anti-Bacterial Agents↗
PubMed1985

Effect of netilmicin on the phospholipid composition of subcellular fractions of rat renal cortex.

The purpose of this study was to determine the subcellular site(s) of the renal cortical phospholipidosis induced by aminoglycosides. For this purpose we injected male Sprague-Dawley rats s.c. with netilmicin, containing tracer quantities of [3H]netilmicin, at 100 mg/kg/day for 2 days; control rats were injected with saline. Twenty-four hours after the second injection of drug the rats were sacrificed and the renal cortex was fractionated by differential ultracentrifugation and Percoll gradient density techniques to obtain purified lysosomes, mitochondria, microsomes, brush border membranes and basolateral membranes. The total phospholipid content of the renal cortex was 300 +/- 5 nmol/mg of protein in control rats and 340 +/- 5 nmol/mg of protein in netilmicin-injected rats. The total phospholipid content of the lysosomal fraction of netilmicin rats, which was enriched in myeloid bodies and [3H]netilmicin, was 91% greater than that of control rats and reflected significant increases of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. This pattern is identical to that reported previously for the rat renal cortical phospholipidosis induced by aminoglycosides. The total phospholipid contents of the mitochondrial, microsomal, brush border membrane and basolateral membrane fractions of netilmicin-injected rats were higher by approximately 10% than the respective fractions of control rats and each fraction exhibited a significant increase of one or more of the four phospholipids elevated in the renal cortical homogenate and in the lysosomal fraction. The data indicate that the myeloid body is the primary source of the lysosomal phospholipidosis induced by netilmicin which provides support for the hypothesis that the lysosomal phospholipidosis is secondary to aminoglycoside-induced inhibition of phospholipid degradation. In addition the findings of increased phospholipid content and altered phospholipid composition of the other subcellular fractions raise the possibility that aminoglycoside antibiotics cause a more generalized disturbance of phospholipid metabolism characterized by altered synthesis as well as degradation in renal proximal tubular cells.

Acetylglucosaminidase↗
PubMed1980

Resistance factors: influence on netilmicin activity.

Netilmicin is active against many but not all bacterial strains that have acquired resistance to aminoglycosides. Generally, netilmicin is 1) active against strains that produce enzymes inhibiting aminoglycosides by phosphorylation or adenylation. Some of these enzymes are widely distributed in aminoglycoside resistant strains, e.g. the adenylating enzyme ANT(2") predominating in resistant Klebsiella and common in resistant Pseudomonas and Serratia strains. Netilmicin either lacks the hydroxyl groups that are the targets for these enzymes or blocks the enzymes through steric hindrance, e.g. by an ethyl group being added to an amino group of the 2-deoxystreptamine. 2) Netilmicin is active or not active against strains producing acetylating enzymes depending on the specific type of enzyme. Thus netilmicin is variably active against strains producing the frequently occurring enzymes of the AAC(3) group mainly found in Pseudomonas but also among Enterobacteriaceae. Providencia and Proteus rettgeri synthesizing AAC(2') are resistant to netilmicin. Bacteria producing enzymes that will acetylate the amino group in the 6' position may be resistant to all currently used aminoglycosides. These enzymes are mainly found in Pseudomonas, Serratia and Staphylococcus. 3) Netilmicin is not active against bacteria resistant to all other aminoglycosides due to reduced cell wall permeability.

Bacteria↗
PubMed1980

Evaluation of netilmicin susceptibility discs using bacteria with known aminoglycoside resistance patterns: correlation of in vitro and in vivo test results.

Data obtained with 30 micrograms netilmicin discs on Mueller-Hinton agar have been compared to MIC values obtained in Mueller-Hinton broth. Regression analysis was used to determine susceptibility cutoff points for Pseudomonas and non-Pseudomonas gram-negatives. The utility of these cutoff points for the determination of netilmicin sensitivity was evaluated in tests with 1405 clinical isolates. These tests employed 897 sensitive isolates and 508 strains with known aminoglycoside resistance patterns. Netilmicin was shown to be active against sensitive isolates and those strains with resistance patterns corresponding to the presence of: ANT(2"), ANT(2")+AAC(6'), ANT(4'), APH(2")+AAC(6'), APH(3')-IV and AAC(3)-I modifying enzymes. PD50 values obtained in experimental mouse infection studies with gentamicin, tobramycin and amikacin as well as netilmicin confirmed the excellent activity of netilmicin against strains with the above-mentioned resistance patterns. The good correlation between disc sensitivity test results and MIC and PD50 values suggest that a 30 micrograms netilmicin disc can be used to predict the netilmicin susceptibility of clinical isolates.

Aminoglycosides↗
PubMed1980

Netilmicin: chemical development and overview of clinical research.

Netilmicin is a new semisynthetic aminoglycoside which was developed by Schering Corporation, USA, for the treatment of serious gram-negative and staphylococcal infections. Nephrotoxicity and ototoxicity in animal studies have indicated that netilmicin is both quantitatively and qualitatively safer than other aminoglycosides. Also, netilmicin has a broader spectrum of activity than either gentamicin or tobramycin. 37 clinical studies were conducted by 29 investigators in 10 countries. 840 courses of treatment in 960 infection sites were analyzed for effectiveness. Of the 724 courses in which a clinical determination could be made, 91% had either complete resolution or improvement. Bacteriologic responses were available for 782 infecting organisms and showed an 82% elimination rate. The pharmacokinetic profile of netilmicin permits twice daily administration in most patients with systemic infections and in all patients with urinary tract infections. The clinical safety of netilmicin was measured in 890 evaluable treatment courses, and only 0.4% auditory reactions, 0.6% vestibular reactions, and 0.9% renal reactions were considered to be probably netilmicin related, when netilmicin was given as recommended.

Adolescent↗
PubMed1982

[Netilmicin in refractory urinary tract infections. Good therapeutic effect in spite of long dosage intervals].

Aminoglycoside antibiotics are useful--despite potential toxicity--for treating urinary tract infection when other antibacterial agents have failed to eradicate bacteriuria. That this is true of the recently introduced aminoglycoside netilmicin was shown by 16 cases of tenacious and frequently recurring urinary tract infection. In contrast to previous recommendations, but relying on well known pharmacokinetic data which show prolonged urinary excretion of aminoglycosides, netilmicin was administered according to the following dosage schedule: Intramuscular injections of 3 mg/kg in cases where renal function was unimpaired, and of 2 mg/kg where it was reduced, were administered at dosage intervals of 1 to 4 days. Peak serum levels of netilmicin measured 1 hour after intramuscular injection were within the expected range of 8-14 micrograms/ml (3 mg/kg) and 6-10 micrograms/ml (2 mg/kg). As a result of the long dosage intervals the serum trough levels were usually far below 1 microgram/ml except in patients with moderate renal failure. Urinary concentrations of netilmicin, however, remained for the most part above the limit of antibacterial activity throughout the dosage intervals of 1 to 4 days. One week after the usual three weeks treatment course, urinary concentrations were still between 1 and 5 mcg/ml, and slowly decreasing amounts of the drug could be detected at least in traces up to 3 months beyond the last dose. Considering the type of urinary tract infections selected to receive netilmicin, the response to treatment was satisfactory and seemed unaffected by the long dosage intervals. Bacteriological cure was achieved in 5 of 11 infections associated with chronic pyelonephritis or analgesic nephropathy and in 4 of 5 urinary infections in patients with renal transplants. Treatment failures could be accounted for by obstructive lesions, stones, and in one transplanted patient by infection localized to her own shrunken kidneys. No instance of ototoxicity or nephrotoxicity due to netilmicin could be detected. Netilmicin administered according to the dosage schedule described can be recommended for ambulatory treatment of tenacious, recurring urinary tract infections due to gram-negative bacteria and refractory to cure by the usual oral antibiotic therapy.

Drug Administration Schedule↗
PubMed1997

Pharmacokinetics and tissue residues of netilmicin and vancomycin in chickens.

Following a single intravenous injection of 10 mg netilmicin or 30 mg vancomycin/kg b.w. to normal chickens, the tested drugs obeyed a two or three compartments open model, with half-lives of distribution of 0.30 and 0.20 hours, respectively. The elimination half-lives following intravenous injection were 0.41 and 4.85 hours, respectively. Following a single intramuscular injection of 10 mg netilmicin or 30 mg vancomycin/kg b.w. to normal chickens, the serum drug concentrations peaked 2 hours post-injection with half-lives of absorption equal to 0.63 and 0.56 hours, respectively. The mean systemic bioavailability of netilmicin and vancomycin following a single intramuscular administration in normal chickens was 27.29 and 43.61%, respectively. These values indicated a limited and moderate absorption for netilmicin and vancomycin from intramuscular site, respectively. During repeated intramuscular administrations of both antibiotics for five consecutive days in normal chickens, the serum drug concentrations peaked two hours post each dose. The drugs concentrations during multiple dosage regimens were significantly increased in 2nd, 3rd, 4th and 5th days in comparison to the 1st day. Netilmicin and vancomycin persisted in liver and kidney for 96 and 120 hours, respectively, after the last intramuscular administration. The withdrawal time of netilmicin and vancomycin could be considered as five and six days, respectively. The in-vitro protein binding percents of netilmicin and vancomycin were 7.45 and 5.81%, respectively.

Animals↗
PubMed1976

In vitro synergistic effect of netilmicin, a new aminoglycoside antibiotic.

The combination of netilmicin (Sch 20569) with carbenicillin, cefazolin, chloramphenicol, and clindamycin was evaluated by in vitro tests against 91 clinical isolates of Pseudomonas, Klebsiella, and Escherichia coli. Combinations were considered to show synergy if there was a fourfold or greater reduction in minimal inhibitory concentration values of both antibiotics when combined. Synergy of netilmicin with carbenicillin could be demonstrated against 21 of 46 Pseudomonas isolates. Comparison of the synergy of carbenicillin with netilmicin or gentamicin showed that netilmicin was less active than gentamicin against Pseudomonas aeruginosa. However, at therapeutic concentrations of the antibiotics, significant differences were not observed. Synergy of netilmicin and cefazolin was demonstrated against only 1 of 21 Klebsiella strains tested, but partial synergy was found for 12 of 20 isolates. Synergy and antagonism were uncommon with the netilmicin-chloramphenicol and netilmicin-clindamycin combinations against E. coli and Pseudomonas.

Anti-Bacterial Agents↗
PubMed1978

Comparison of netilmicin with gentamicin in the therapy of experimental Escherichia coli meningitis.

Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental Escherichia coli meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 10(5)E. coli colony-forming units. The minimum bactericidal concentration was 2 mug/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) x 100%] was 22.5 +/- 6.0 and 20.6 +/- 7.2 for netilmicin and gentamicin, respectively (P = 0.18). However, netilmicin achieved bactericidal activity in the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 mug/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 mug of netilmicin per ml as compared to 14.1 mug of gentamicin per ml. Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.

Animals↗
PubMed1984

Evaluation of five immunological methods for the assay of serum netilmicin.

Three specific immunological methods for the determination of netilmicin and two enzyme immunoassays for gentamicin were compared for assaying serum netilmicin. The commercial kits we used were Radioimmunoassay (RIA), Substrate Labelled Fluorescence Immunoassay (gentamicin) ( SLFIA ), Homogeneous Enzyme Immunoassay (gentamicin and netilmicin) (EMIT) and Fluorescence Polarization Immunoassay ( FPIA ). After analysing spiked calf serum samples in the range of 0-15.8 mg X 1(-1) netilmicin, extensive statistical analysis was performed. The Performance Index was used to qualify the different methods. Results show that the SLFIA (gentamicin) kit is a very acceptable method for the determination of serum netilmicin levels, well comparable with the EMIT (gentamicin) kit and the EMIT (netilmicin) kit. FPIA and RIA require expensive specialized apparatus so it is only economically feasible when other drugs or substances are also determined on the same apparatus. The abilities and specific needs of each laboratory will play an important role in the choice of a method, because the tested kits are all within the range we need from a clinical point of view.

Analysis of Variance↗
PubMed1979

Clinical evaluation of netilmicin therapy in serious infections.

Netilmicin, a new semisynthetic aminoglycoside, was evaluated in the therapy of 33 episodes of infection in 30 patients. Eighteen patients had documented bacteremia. Infection sites included pulmonary, urinary tract and soft tissue areas. A complete bacteriologic and clinical cure rate of 85 per cent was achieved. No treatment failures occurred in the bacteremic group. Although netilmicin is less effective than gentamicin in vitro against Pseudomonas, it was clinically and bacteriologically effective. Netilmicin bacteriologic cures occurred in patients whose organisms were inhibited by 6.2 microgram/ml or less of netilmicin. Despite a uniform dosing protocol, a wide range of netilmicin serum levels was obtained. Adverse effects were limited to one case of transient nephrotoxicity and one Candida urinary suprainfection. Netilmicin appears to be an effective, safe agent for the therapy of serious infections.

Adult↗
PubMed1990

Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone.

PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.

Adolescent↗