imen with less than four drugs may be considered. streptomycin is also indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. the management of tuberculosis has become more complex as a consequence of increasing rates of drug resistance and concomitant hiv infection. additional consultation from experts in the treatment of tuberculosis may be desirable in those settings. non-tuberculosis infections: the use of streptomycin should be limited to the treatment of infections caused by bacteria which have been shown to be susceptible to the antibacterial effects of streptomycin and which are not amenable to therapy with less potentially toxic agents. yersinia pestis (plague), francisella tularensis (tularemia), brucella , calymmatobacterium granulomatis (donovanosis, granuloma inguinale), h. ducreyi (chancroid), h. influenzae (in respiratory, endocardial, and meningeal infections-concomitantly with another antibacterial agent), k. pneumoniae pneumonia (concomitantly with another antibacterial agent), e.coli, proteus, a. aerogenes, k. pneumoniae, and enterococcus faecalis in urinary tract infections, streptococcus viridans , enterococcus faecalis (in endocardial infections - concomitantly with penicillin), gram-negative bacillary bacteremia (concomitantly with another antibacterial agent). to reduce the development of drug-resistant bacteria and maintain the effectiveness of streptomycin and other antibacterial drugs, streptomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

streptomycin readily crosses the placental barrier, caution in use of the drug is important to prevent ototoxicity in the fetus. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. clostridium difficile associated diarrhea clostridium difficile associated diarrhea (cdad) has been reported with use of nearly all antibacterial agents, including streptomycin for injection, and may range in severity from mild diarrhea to fatal colitis. treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of c. difficile. c. difficile produces toxins a and b which contribute to the development of cdad. hypertoxin producing strains of c. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. cdad must be considered in all patients who present with diarrhea following antibiotic use. careful medical history is necessary since cdad has been reported to occur over two months after the administration of antibacterial agents. if cdad is suspected or confirmed, ongoing antibiotic use not directed against c. difficile may need to be discontinued. appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of c. difficile, and surgical evaluation should be instituted as clinically indicated. risk of ototoxicity due to mitochondrial dna variants cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12s rrna gene ( mt-rnr1 ), particularly the m.1555a>g variant. ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. mitochondrial dna variants are present in less than 1% of the general us population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown. in case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial dna variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies.

n severely uremic patients a single dose may produce high blood levels for several days and the cumulative effect may produce ototoxic sequelae. when streptomycin must be given for prolonged periods of time, alkalinization of the urine may minimize or prevent renal irritation. a syndrome of apparent central nervous system depression, characterized by stupor and flaccidity, occasionally coma and deep respiratory depression, has been reported in very young infants in whom streptomycin dosage had exceeded the recommended limits. thus, infants should not receive streptomycin in excess of the recommended dosage. in the treatment of venereal infections such as granuloma inguinale, and chancroid, if concomitant syphilis is suspected, suitable laboratory procedures such as a dark field examination should be performed before the start of treatment, and monthly serologic tests should be done for at least four months. as with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. if superinfection occurs, appropriate therapy should be instituted.

for more severe or fulminating infections (endocarditis, meningitis, etc.), the physician should always take adequate measures to be immediately aware of any toxic signs or symptoms occurring in the patient as a result of streptomycin therapy. 1. tuberculosis: the standard regimen for the treatment of drug susceptible tuberculosis has been two months of inh, rifampin and pyrazinamide followed by four months of inh and rifampin (patients with concomitant infection with tuberculosis and hiv may require treatment for a longer period). when streptomycin is added to this regimen because of suspected or proven drug resistance (see indications and usage section), the recommended dosing for streptomycin is as follows: daily twice weekly thrice weekly children 20-40 mg/kg max 1 g 25-30 mg/kg max 1.5 g 25-30 mg/kg max 1.5 g adults 15 mg/kg max 1 g 25-30 mg/kg max 1.5 g 25-30 mg/kg max 1.5 g streptomycin is usually administered daily as a single intramuscular injection. a total dose of not more than 120 g over the course of therapy should be given unless there are no other therapeutic options. in patients older than 60 years of age, the drug should be used at a reduced dosage due to the risk of increased toxicity. (see boxed warning .) therapy with streptomycin may be terminated when toxic symptoms have appeared, when impending toxicity is feared, when organisms become resistant, or when full treatment effect has been obtained. the total period of drug treatment of tuberculosis is a minimum of 1 year; however, indications for terminating therapy with streptomycin may occur at any time as noted above. 2. tularemia: one to 2 g daily in divided doses for 7 to 14 days until the patient is afebrile for 5 to 7 days. 3. plague: two grams of streptomycin daily in two divided doses should be administered intramuscularly. a minimum of 10 days of therapy is recommended. 4. bacterial endocarditis: a . streptococcal endocarditis: in penicillin-sensitive alpha and non-hemolytic streptococcal endocarditis (penicillin mic ≤0.1 mcg/ml), streptomycin may be used for 2-week treatment concomitantly with penicillin. the streptomycin regimen is 1 g b.i.d. for the first week, and 500 mg b.i.d. for the second week. if the patient is over 60 years of age, the dosage should be 500 mg b.i.d. for the entire 2-week period. b. enterococcal endocarditis : streptomycin in doses of 1 g b.i.d. for 2 weeks and 500 mg b.i.d. for an additional 4 weeks is given in combination with penicillin. ototoxicity may require termination of the streptomycin prior to completion of the 6-week course of treatment. 5. concomitant use with other agents: for concomitant use with other agents to which the infecting organism is also sensitive: streptomycin is considered a second-line agent for the treatment of gram-negative bacillary bacteremia, meningitis, and pneumonia; brucellosis; granuloma inguinale; chancroid, and urinary tract infection. for adults: 1 to 2 grams in divided doses every six to twelve hours for moderate to severe infections. doses should generally not exceed 2 grams per day. for children: 20 to 40 mg/kg/day (8 to 20 mg/lb/day) in divided doses every 6 to 12 hours. (particular care should be taken to avoid excessive dosage in children). the dry lyophilized cake is dissolved by adding water for injection usp in an amount to yield the desired concentration as indicated in the following table: approx. conc. mg/ml volume (ml) of solvent 200 4.2 250 3.2 400 1.8 sterile reconstituted solutions should be protected from light and may be stored at room temperature for one week without significant loss of potency. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

ms generally appear early and usually are reversible with early detection and cessation of streptomycin administration. two to three months after stopping the drug, gross vestibular symptoms usually disappear, except from the relative inability to walk in total darkness or on very rough terrain. although streptomycin is the least nephrotoxic of the aminoglycosides, nephrotoxicity does occur rarely. clinical judgment as to termination of therapy must be exercised when side effects occur. for medical advice about adverse reactions contact your medical professional. to report suspected adverse reactions, contact xgen pharmaceuticals djb, inc. at 1-866-390-4411 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

ainst 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 , yersinia pestis streptococcus viridans , enterococcus faecalis (in endocardial infections - concomitantly 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 procedure 1 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: interpretive criteria for enterobacteriaceae 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 2 : acceptable control ranges organism zone diameter (mm) e. coli atcc 25922 12-20 interpretive criteria for agents of bioterrorism organism mic range (mcg/ml) (s) susceptible (i) intermediate (r) resistant yersinia pestis ≤4 8 ≥16 francisella tularensis ≤8 there are no intermediate or resistant criteria brucella ≤8

taken the last dose of the antibiotic. if this occurs, patients should contact their physician as soon as possible.