Sisomicin Treatment of Complicated Urinary Tract Infections: Efficacy, Tolerance and Pharmacokinetics

Welling, Peter G.; Mosegaard, Aage; Madsen, Paul O.

doi:10.1002/j.1552-4604.1974.tb01372.x

Cited by 24 publications

(7 citation statements)

References 4 publications

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“…t1/2 values for the other subjects were in the range reported by others (4,6,12,15,16). In most cases, postinfusion serum concentrations obtained in the subjects of this sample population agree with concentrations obtained after administering the drug at the dose of 1.0 mg/kg to volunteers (7) and elderly male patients suffering from urinary tract infections (16). Several patients had higher steady-state serum concentrations than predicted by our pharmacokinetic model.…”

Section: Discussionsupporting

confidence: 86%

“…Two of the three children with very short t4/2 had cystic fibrosis, a condition previously associated with increased excretion rates of dicloxacillin and methicillin (17). t1/2 values for the other subjects were in the range reported by others (4,6,12,15,16). In most cases, postinfusion serum concentrations obtained in the subjects of this sample population agree with concentrations obtained after administering the drug at the dose of 1.0 mg/kg to volunteers (7) and elderly male patients suffering from urinary tract infections (16).…”

Section: Discussionmentioning

confidence: 55%

“…There was no significant correlation between serum clearance or ti,/2 and percentage of dose excreted within the three dosage intervals where urinary levels were measured. This indicates that in children, as well as in adults (16), there is a variable but significant contribution of infusion and excretion rates, as well as extrarenal VOL. 13,1978 on May 10, 2018 by guest http://aac.asm.org/ Downloaded from…”

Section: Discussionmentioning

confidence: 96%

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Clinico-Pharmacological Studies of Sisomicin in Ill Children

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Vose

Hammerberg

et al. 1978

Antimicrob Agents Chemother

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Sisomicin, at 4.5 mg/kg per day, was prescribed for the therapy of serious bacterial infections of hospitalized infants, children, and adolescents. Eleven children received full treatment courses, with 10 clinical and 9 bacteriological cures. Three patients with underlying disease (two cystic fibrosis and one aplastic anemia) accounted for the failures. Mean half-life was 98.3 min (range, 26.1 to 159.3), and peak serum concentrations 10 min after intravenous infusion were similar (5 to 6 ,g/ml) on days 1, 3, and 5 of therapy. Mean urinary concentrations were 54.3 isg/ml; 31 to 47% of the drug was excreted within the 8-h dosage interval.The drug was tolerated well by all patients; however, one patient, receiving the longest duration of therapy (26 days), developed reversible nephrotoxicity.The emergence of gentamicin-resistant bacteria in hospitalized patients has emphasized the importance of evaluating alternative antibiotics. Sisomicin is a new aminoglycoside antibiotic derived from the fermentation broth of Micromonospora inyoenis that has many properties in common with gentamicin as well as the advantage of activity against selected gentamicinresistant bacteria (4,6,9,14). The purpose of this study was to examine some of the pharmacokinetic, clinical, and toxicological properties of sisomicin in the therapy of serious infections of children. MATERIALS AND METHODSSisomicin was administered to 12 patients hospitalized at the Montreal Children's Hospital. These patients were selected by the attending physician as candidates for aminoglycoside therapy using standard clinical and laboratory criteria. Once a patient was selected to receive aminoglycosides, sisomicin was offered in lieu of gentamicin after carefully explaining the nature of the study and the differences between the two drugs to the parents and only after obtaining informed consent. Appropriate bacterial cultures and base-line laboratory studies were obtained in each case. When positive cultures were obtained before therapy, appropriate cultures were repeated during and after therapy as well. Sisomicin was administered in a dosage of4.5 mg/kg per day intravenously (divided every 8 h) over 0.5 h, and the duration of treatment was determined by standard clinical and bacteriological criteria.All patients were carefully examined for tolerance to the drug and for hematological, hepatic, and renal toxicities by the following tests: hemoglobin, hematocrit, white blood count and differential, platelets, serum glutamic oxaloacetic transa inase, bilirubin, alkaline phosphatase; urea nitrogen, creatinine, and urinalysis. These tests were carried out before, during, and after therapy.Audiological evaluations were performed within 72 h of initiation of therapy, and again after completion of the course of sisomicin. School-age children were studied by standard pure-tone and standard speech audiometry and impedance testing, pre-school children and infants by behavioral observation, play, and conditioned orienting response audiometry, and impedance measurements when...

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 96%

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Clinico-Pharmacological Studies of Sisomicin in Ill Children

Marks

Vose

Hammerberg

et al. 1978

Antimicrob Agents Chemother

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“…In patients with normal renal function (group which would indicate distribution and sequestration I), the half-life of netilmicin is approximately in the in deeper compartments followed by slow release and same range as that reported for tobramycin (Pechere elimination. This study also revealed that a 2 -comand Dugal, 1976;Regamey et aI., 1973) and partment kinetic model was found to adequately sisomicin (Pechere et aI., 1976;Welling et al, 1974). describe the time course of gentamicin, by collecting The present data also indicate that the major route of urine for longer times and assaying postmortem.…”

Section: Discussionsupporting

confidence: 56%

Pharmacokinetics of Netilmicin in Renal Insufficiency and Haemodialysis

Péchère

Dugal

Pechere

1978

Clinical Pharmacokinetics

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The pharmacokinetics of intravenously administered netilmicin, an investigational aminoglycoside antibiotic, were studied in 38 patients with creatinine clearance ranging from 150 to Oml/min/1.73m2 in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum disappearance of netilmicin followed first order kinetics and the elimination rate constant decreased proportionally with decreasing renal function. Half-lives averaged 2.2 hours in normal individuals (creatinine clearance greater than 80ml/min/1.73m2) and reached 42 +/- 10 hours (mean +/- SD) in virtually anephric patients. The elimination rate constant lowered proportionally with decreasing renal function. Several linear relationships between pharmacokinetic parameters and renal function indicators were defined. A clinically useful correlation indicates that the half-life may be approximated as 3 times the serum creatinine concentration and may be used for adjustment of dosage of netilmicin in the treatment of patients with impaired renal function. During haemodialysis, netilmicin extraction from the blood reaches 75 +/- 14% (mean +-/ 95% confidence interval) of that of creatinine and 88 +/- 19% of that of blood urea nitrogen.

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“…0.43 + 0.08 in the subjects of group 1 and 0.33 0.08 in the subjects of group 2. Sisomicin clearances less than half that of creatinine have been recently reported (12) In the early stages after administration of a single 1-mg/kg intravenous dose, serum levels in moderately and severely renal-impaired patients are comparable to those obtained in normal volunteers. This would suggest that concern over the influence of renal impairment of sisomicin parmacokinetics may be limited to modifications in elimination.…”

Section: Resultsmentioning

confidence: 78%

Clinical Pharmacokinetics of Sisomicin: Dosage Schedules in Renal-Impaired Patients

Péchère

Pechere²,

Dugal³

1976

Antimicrob Agents Chemother

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The pharmacokinetics of intravenously administered sisomicin were studied in 33 patients with normal renal function and different degrees of renal impairment. In all patients, the serum disappearance of sisomicin, once distribution equilibrium had been achieved, followed first-order kinetics and percentage of hourly loss from serum decreased proportionally with decreasing renal function. Half-lives averaged 2.06 h in normal subjects (endogenous creatinine clearance greater than 80 ml/min per 1.73 M2) and reached 35.3 h in a virtually anephric subject. Linear relationships were defined between sisomicin serum half-life and the reciprocal of the endogenous creatinine clearance and serum creatinine concentration. The latter relationship indicates that the half-life of sisomicin may be approximated as twice the serum creatinine concentration and may be used for dosage adjustment in renal-impaired patients. Prediction of the extent of sisomicin removal by hemodialysis may be made from the relationship between the dialyzate of sisomicin and that of creatinine and blood urea nitrogen. Dosage schedules and methods of administration compatible with the pharmacokinetic properties of the antibiotic are finally proposed.

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Sisomicin Treatment of Complicated Urinary Tract Infections: Efficacy, Tolerance and Pharmacokinetics

Cited by 24 publications

References 4 publications

Clinico-Pharmacological Studies of Sisomicin in Ill Children

Clinico-Pharmacological Studies of Sisomicin in Ill Children

Pharmacokinetics of Netilmicin in Renal Insufficiency and Haemodialysis

Clinical Pharmacokinetics of Sisomicin: Dosage Schedules in Renal-Impaired Patients

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