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Streptomycin

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Streptomycin

CLINICAL PHARMACOLOGY

Following intramuscular injection of 1 g of streptomycin as the sulfate, a peak serum level of 25 to 50 mcg/mL is reached within 1 hour, diminishing slowly to about 50 percent after 5 to 6 hours.

Appreciable concentrations are found in all organ tissues except the brain. Significant amounts have been found in pleural fluid and tuberculous cavities. Streptomycin passes through the placenta with serum levels in the cord blood similar to maternal levels. Small amounts are excreted in milk, saliva, and sweat.

Streptomycin is excreted by glomerular filtration. In patients with normal kidney function, between 29% and 89% of a single 600 mg dose is excreted in the urine within 24 hours. Any reduction of glomerular function results in decreased excretion of the drug and concurrent rise in serum and tissue levels.

Microbiology

Streptomycin sulfate is a bactericidal antibiotic. It acts by interfering with normal protein synthesis. Streptomycin has been shown to be active against most strains of the following organisms both in vitro and in clinical infection. (See INDICATIONS AND USAGE.):

Brucella (brucellosis),
Calymmatobacterium granulomatis
(donovanosis, granuloma inguinale),
Escherichia coli, Proteus spp., Aerobacter aerogenes, Klebsiella pneumoniae,
and Enterococcus faecalis in urinary tract infections,
Francisella tularensis,

Haemophilus ducreyi
(chancroid),
Haemophilus influenzae
(in respiratory, endocardial, and meningeal infections - concomitantly with another antibacterial agent),
Klebsiella pneumoniae
pneumonia (concomitantly with another antibacterial agent),
Mycobacterium tuberculosis
,
Pasteurella pestis

Streptococcus
viridans, Enterococcus faecalis (in endocardial infectionsconcomitantly with penicillin).

SUSCEPTIBILITY TESTS: Diffusion Techniques

Quantitative methods that require measurement of zone diameters give the most precise estimate of the susceptibility of bacteria to antimicrobial agents. One such standard procedure1 which has been recommended for use with disks to test susceptibility of organisms to streptomycin uses the 10 mcg streptomycin disk. Interpretation involves the correlation of the diameter obtained in the disk test with the minimum inhibitory concentration (MIC) for streptomycin.

Reports from the laboratory giving results of the standard single disk susceptibility test with a 10 mcg streptomycin disk should be interpreted according to the following criteria:

Zone Diameter (mm) Interpretation
≥15 (S) Susceptible
11- 12 (I) Intermediate
≤10 (R )Resistant

A report of “Susceptible” indicates that the pathogen is likely to respond to monotherapy with streptomycin. A report of “Intermediate” indicates that the result be considered equivocal, and, if the organism is not fully susceptible to alternative clinically feasible drugs, the test should be repeated. This category provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretations. A report of “Resistant” indicates that achievable drug concentrations are unlikely to be inhibitory and other therapy should be selected.

Standardized procedures require the use of laboratory control organisms. The 10 mcg streptomycin disk should give the following zone diameter:

Organism Zone Diameter (mm)
E. coli ATCC 25922 12-20
S. aureus ATCC 259 23 14-22

Methods Section

Two standardized in vitro susceptibility methods are available for testing streptomycin against Mycobancerium tuberculosis organisms. The agar proportion method (CDC or NCCLS M24-P) utilizes middlebrook 7H10 medium impregnated with streptomycin at two final concentrations, 2.0 and 10.0 mcg/mL. MIC90 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug ≥1% of the control indicates resistance.

The radiometric broth method employs the BACTEC 460 machine to compare the growth index from untreated control cultures to cultures grown in the presence of 6.0 mcg/mL of streptomycin. Strict adherence to the manufacturer's instructions for sample processing and data interpretation is required for this assay.

Susceptibility test results obtained by these two different methods cannot be compared unless equivalent drug concentrations are evaluated.

The clinical relevance of in vitro susceptibility test results for mycobacterial species other than M. tuberculosis using either the BACTEC or the proportion method has not been determined.

REFERENCES

'National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests-Fourth Edition. Approved Standard NCCLS Document M2-A4.Vol.10, No.7, NCCLS, Villanova, PA 1990.

Last reviewed on RxList: 6/20/2008
This monograph has been modified to include the generic and brand name in many instances.

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