Netilmicin Sulfate: A Comparative Evaluation of Antimicrobial Activity, Pharmacokinetics, Adverse Reactions and Clinical Efficacy

Craig, William A.; Guðmundsson, Sigurður; Reich, R.

doi:10.1002/j.1875-9114.1983.tb03283.x

Cited by 12 publications

(3 citation statements)

References 98 publications

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“…The AUC and Vs, reported for both vancomycin and netilmicin are similar to those reported in the literature for patients not undergoing CPB (6,24). Vancomycin and netilmicin demonstrated a decrease in renal clearance during CPB, although there was not a statistically significant difference (P > 0.05) between the three phases.…”

Section: Resultssupporting

confidence: 84%

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition

Klamerus

Rodvold

Silverman

et al. 1988

Antimicrob Agents Chemother

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The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased. Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per mi2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).Antimicrobial prophylaxis for cardiopulmonary bypass (CPB) surgery is routinely prescribed to prevent endocarditis or sternal and costochondral infections (7, 26). Selection of an appropriate antibiotic is directed against Staphylococcus aureus and Staphylococcus epidermidis, which account for the majority of bacterial infections, and also against the gram-negative bacilli (2, 3, 7, 26). The increasing incidence of methicillin-resistant staphylococci has led to the recommendation that vancomycin be administered prophylactically for cardiothoracic surgery in hospitals in which methicillin-resistant staphylococci are prevalent (3,15,16). Aminoglycosides have been recommended for prophylaxis against the gram-negative pathogens on the cardiac valves and the sternum and for some prophylactic effect against staphylococci (16).Many physiologic changes occur in patients placed on CPB. These changes, including decreased cardiac output and organ perfusion, can alter drug absorption, distribution, metabolism, and excretion (13,14). Studies with prophylactic vancomycin and netilmicin in CPB surgery are very limited. Only two reports have examined vancomycin concentrations in serum during CPB surgery, and both sought to determine appropriate dosing, rather than drug disposition (4, 10).One published report of aminoglycoside prophylaxis in open-heart surgery has addressed netilmicin concentrations in pericardial fluid, atrial appendage, and serum but only in the intraoperative phase of CPB (27). Therefore, this study was designed to investigate what effect CPB surgery has on the disposition of two renally excreted prophylactic antibiotics, vancomycin and netilmicin, before, during, and after CPB. MATERIALS AND METHODSA total of 10 adult patients scheduled for elective coronary artery bypass grafting or cardiac valve replacement surgery requiring CPB were studied. All patients gave written informed consent to participate in this protocol, which was * Corresponding author....

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Section: Resultssupporting

confidence: 84%

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition

Klamerus

Rodvold

Silverman

et al. 1988

Antimicrob Agents Chemother

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“…Netilmicin (Schering‐Plough, Madrid, Spain) is a semisynthetic aminoglycoside active against a wide range of Gram‐negative and some Gram‐positive bacteria, including many gentamycin‐resistant strains [1, 2]. Aminoglycosides continue to play an important role in the treatment of diverse kinds of infections and are among the most widely used antimicrobial agents for hospitalized patients.…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of netilmicin in short‐term prophylactic treatment

Jauregizar¹,

Wald²,

Astobieta³

et al. 2003

Brit J Clinical Pharma

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AimsTo characterize the population pharmacokinetics of netilmicin, an aminoglycoside antibiotic, in adult urology patients and to develop a covariate model for improved dose titration. Methods Data from 62 adult patients (55 male, seven female), undergoing urological surgery and treated with netilmicin for short-term prophylaxis, were evaluated retrospectively. The group had (median, range) ages 68, 31-92 years, weights 72, 43-106 kg and heights 167, 148-182 cm. No patient showed renal impairment before netilmicin treatment (serum creatinine £ 1.9 mg dl -1 ). Netilmicin (100 mg) was administered as a maximum of four successive intravenous infusions of 30 min, at 8-h intervals. A total of five blood samples were collected from each patient. Prior to analysis, the dataset was divided into 'index' ( n = 44) and 'validation' ( n = 18) groups at random. The time courses of netilmicin concentrations from all subjects were analysed using a mixed effects, population, nonlinear modelling package (WinNonMix). For covariate model development, a stepwise procedure was used with backward elimination followed by forward inclusion based on age, sex, weight, height, creatinine clearance and type of surgery. The final covariate model parameters from the index group were used to simulate concentrations in the validation group and the bias and precision were compared with the observations. Conclusion Bi-compartmental pharmacokinetic parameters of netilmicin have been estimated from clinical data in urological surgery patients using a population approach. A given single dose results in large variability in plasma concentrations and thus the population covariate final model can be used for direct estimation of initial dosing in patients.

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“…Netilmicin, the aminoglycoside antibiotic most recently marketed in the United States, has a spectrum of antibacterial action similar to that of other aminoglycosides (4,6). Due to its activity against Pseudomonas aeruginosa, a common pathogen in the pneumonia of cystic fibrosis (CF) (11), netilmicin has potential application in this setting.…”

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confidence: 99%