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Kantrex

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Kantrex

Kantrex

CLINICAL PHARMACOLOGY

The drug is rapidly absorbed after intramuscular injection and peak serum levels are generally reached within approximately one hour. Doses of 7.5 mg/kg give mean peak levels of 22 g/mL. At 8 hours following a 7.5 mg/kg dose, mean serum levels are 3.2 g/mL. The serum half-life is 2½ hours. Intravenous administration of kanamycin over a period of one hour resulted in serum concentrations similar to those obtained by intramuscular administration.

Kanamycin diffuses rapidly into most body fluids including synovial and peritoneal fluids and bile. Significant levels of the drug appear in cord blood and amniotic fluid following intramuscular administration to pregnant patients. Spinal fluid concentrations in normal infants are approximately 10 to 20 percent of serum levels and may reach 50 percent when the meninges are inflamed.

Studies in normal adult patients have shown only trace levels of kanamycin in spinal fluid. No data are available on adults with meningitis.

The drug is excreted almost entirely by glomerular filtration and is not reabsorbed by the renal tubules. Hence, high concentrations are attained in the nephron, and the urine may contain levels 10 to 20 times higher than those in serum. Little, if any, metabolic transformation occurs. Renal excretion is extremely rapid. In patients with normal renal function, approximately one-half of the administered dose is cleared within 4 hours and excretion is complete within 24 to 48 hours. Patients with impaired renal function or with diminished glomerular filtration pressure excrete kanamycin more slowly. Such patients may build up excessively high blood levels which greatly increase the risk of ototoxic reactions. In severely burned patients the half-life may be significantly decreased and resulting serum concentrations may be lower than anticipated from the mg per kg dose.

Microbiology

Kanamycin sulfate is a bactericidal antibiotic which acts by inhibiting the synthesis of protein in susceptible microorganisms. Kanamycin sulfate is active in vitro against many strains of Staphylococcus aureus (including penicillinase and non penicillinase-producing strains), Staphylococcus epidermidis, N. gonorrhoeae, H. influenzae, E. coli, Enterobacter aerogenes, Shigella and Salmonella species, K. pneumoniae, Serratia marcescens, Providencia species, Acinetobacterspecies and Citrobacter freundii and Citrobacter species, and many strains of both indole-positive and indole-negative Proteus strains that are frequently resistant to other antibiotics.

Aminoglycosides have a low order of activity against most gram-positive organisms including Streptococcus pyogenes, Streptococcus pneumoniae and enterococci. In vitro studies have demonstrated that an aminoglycoside combined with an antibiotic which interferes with cell wall synthesis (ie, Penicillin G or ampicillin) affects some Group D streptococcal strains synergistically. Bacteriological testing and tests for antibiotic synergism are necessary.

Enzymatic inactivation of deoxystreptamine is the principal mechanism of resistance.

Susceptibility Testing

Quantitative methods for susceptibility testing that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure has been recommended for use with discs to test susceptibility to kanamycin. Interpretation involves correlation of the diameters obtained in the disc test with minimal inhibitory concentration (MIC) values for kanamycin.

Reports from the laboratory give results of the standardized single disc susceptibility test (Bauer, et al., Am. J. Clin. Path. 1966; 45:493 and Federal Register 37:20525-20529, 1972), using a 30-g kanamycin disc should be interpreted according to the following criteria:

Organisms producing zones of 18 mm or greater, or MIC's of 16 g or less are considered susceptible, indicating that the test organism is likely to respond to therapy.

Resistant organisms produce zones of 14 mm or less or MIC's of 16 g or greater. A report of "resistant" from the laboratory indicates that the infecting organism is not likely to respond to therapy.

Zones greater than 14 mm and less than 18 mm, or MIC's of greater than 16 g and less than 65 g, indicate intermediate susceptibility. A report of "intermediate" susceptibility suggests that the organism would be susceptible if the infection is confined to tissues and fluids (eg, urine), in which high antibiotic levels are attained.

Control organisms are recommended for susceptibility testing. Each time the test is performed one or more of the following organisms should be included: Escherichia coli ATCC 15922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853. The control organisms should produce zones of inhibition within the following ranges:

Escherichia coli (ATCC 15922) 22-30 mm
Staphylococcus aureus (ATCC 25923) 22-31 mm
Pseudomonas aeruginosa (ATCC 27853) 17-23 mm

Last reviewed on RxList: 10/8/2008
This monograph has been modified to include the generic and brand name in many instances.

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