VA Class:AM300

AHFS Class:

• Aminoglycosides 8:12.02

Generic Name(s):

• Streptomycin Sulfate

Associated Monographs

• Aminoglycosides General Statement

Streptomycin is an aminoglycoside antibiotic and antituberculosis agent.1,2,5

Mycobacterial Infections

Active Tuberculosis

Streptomycin is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis.1,2,100,136

The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) currently recommend several possible multiple-drug regimens for the treatment of culture-positive pulmonary tuberculosis.100 These regimens have a minimum duration of 6 months (26 weeks), and consist of an initial intensive phase (2 months) and a continuation phase (usually either 4 or 7 months).100

Streptomycin is considered a second-line agent for use in multiple-drug regimens in patients with relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.100 Although streptomycin can be as effective as ethambutol when used in the initial phase of antituberculosis treatment and was previously included in recommendations for this phase of treatment, M. tuberculosis strains resistant to streptomycin have been reported with increasing frequency worldwide, which makes the drug less useful.100 Therefore, the ATS, CDC, and IDSA state that streptomycin is no longer recommended as being interchangeable with ethambutol for initial regimens unless the strain is known to be susceptible to the drug or the patient is from a population in which streptomycin resistance is unlikely.100

If streptomycin is added as a new drug to a regimen in patients experiencing treatment failure who have proven or suspected drug-resistant tuberculosis, at least 2 (preferably 3) new drugs known or expected to be active against the resistant strain should be added at the same time.100 After results of in vitro susceptibility testing are available, the regimen can be adjusted accordingly.100 Streptomycin-resistant M. tuberculosis may be susceptible to amikacin, kanamycin, and capreomycin.100 Patients with treatment failure or drug-resistant M. tuberculosis should be managed in consultation with an expert in the treatment of tuberculosis.100

For information on general principles of antituberculosis therapy and recommendations regarding specific multiple-drug regimens and duration of therapy, see the Antituberculosis Agents General Statement 8:16.04.

Other Mycobacterial Infections

Streptomycin has been used in conjunction with other antimycobacterial anti-infectives for the treatment of pulmonary infections caused by M. avium complex† (MAC).11,26,136 The ATS and other clinicians recommend use of a multiple-drug regimen of clarithromycin (or azithromycin), ethambutol, and either rifabutin or rifampin for the treatment of pulmonary MAC infections in patients not infected with human immunodeficiency virus (HIV).11,26 Streptomycin can be included during the first 2-3 months of this multiple-drug regimen, especially in those with extensive disease and in those who cannot tolerate other possible agents.11,26 In one prospective, placebo-controlled study in HIV-negative adults, use of streptomycin during the initial 3 months of a clarithromycin, ethambutol, and rifampin regimen resulted in a higher sputum conversion rate but did not improve the sputum relapse rate or improve the overall clinical assessment.11 The ATS states that streptomycin also can be included in multiple-drug regimens used for initial treatment of disseminated MAC infections,26 but streptomycin is not included in current CDC, NIH, and IDSA guidelines for the treatment of disseminated MAC infections in HIV-infected patients.27

Streptomycin has been used in conjunction with other antimycobacterial anti-infectives for the treatment of infections caused by M. kansasii †.26,28,135 A multiple-drug regimen of isoniazid, rifampin, and ethambutol usually is recommended for the treatment of pulmonary or extrapulmonary M. kansasii infections.26,28,135 Some clinicians suggest that streptomycin can be included26,28,135 during the first 2-3 months of this multiple-drug regimen.26,28

Although streptomycin has bactericidal activity against M. leprae in mice40 and has been used in the past for the treatment of leprosy†,41 aminoglycosides are not currently recommended for the treatment of leprosy.2,136

For further information on treatment of other mycobacterial diseases, see the Antituberculosis Agents General Statement 8:16.04.

Brucellosis

Treatment

Streptomycin is used in the treatment of brucellosis.1,13,14,15,17,29,134,135,136 Tetracyclines generally are considered the drugs of choice for the treatment of brucellosis; however, concomitant use of another anti-infective (e.g., streptomycin or gentamicin and/or rifampin) is recommended to reduce the likelihood of relapse, especially for severe infections and when there are complications such as meningitis, endocarditis, or osteomyelitis.13,14,15,134,135,136 Monotherapy is no longer recommended for the treatment of brucellosis since such therapy is associated with high relapse rates.14,29,134,136

A regimen of oral doxycycline and oral rifampin may be effective for the treatment of less severe brucellosis.134,136 For the treatment of acute, complicated brucellosis (e.g., skeletal disease, endocarditis), a regimen of doxycycline (or co-trimoxazole in children younger than 8 years of age) and rifampin, with IM streptomycin given during the first 2-3 weeks usually is recommended.13,15,17,134,136 Gentamicin can be used if streptomycin is unavailable. Although data are limited, alternative regimens that have been suggested for the treatment of brucellosis include co-trimoxazole with or without gentamicin (or streptomycin) or rifampin; ciprofloxacin (or ofloxacin) and rifampin; and chloramphenicol with or without streptomycin.29,134,135,136 For the treatment of neurobrucellosis, a regimen that includes a tetracycline, rifampin, and streptomycin is recommended.13

Prophylaxis

Postexposure prophylaxis with anti-infectives is not generally recommended after possible exposure to endemic brucellosis; however, use of an anti-infective regimen recommended for the treatment of brucellosis (e.g., doxycycline and rifampin) should be considered following a high-risk exposure to Brucella .134 These high-risk exposures include needlestick injuries involving the brucella vaccine available for veterinary use (a brucella vaccine for use in humans is not available); inadvertent laboratory exposure to the organism; or confirmed exposure in the context of biologic warfare or bioterrorism.134

Burkholderia Infections

Some clinicians suggest that streptomycin used in conjunction with a tetracycline is a regimen of choice and streptomycin used in conjunction with chloramphenicol is an alternative for the treatment of glanders† caused by Burkholderia mallei (formerly Pseudomonas mallei ).135 However, experience is limited regarding treatment of human cases and optimum regimens have not been identified.18,134 Some clinicians suggest that, pending results of in vitro susceptibility tests, regimens used for the treatment of melioidosis can be used for initial empiric treatment of glanders.134 Severe melioidosis usually requires an initial parenteral regimen of ceftazidime, imipenem, or meropenem (with or without concomitant co-trimoxazole or doxycycline), followed by a prolonged oral maintenance regimen of doxycycline (in conjunction with co-trimoxazole) or amoxicillin and clavulanate.18,134

The US Army Medical Research Institute of Infectious Diseases (USAMRIID) and European Commission Task Force on Biological and Chemical Agent Threats (BICHAT) state that the same treatment regimens recommended for naturally occurring melioidosis or glanders should be used if these Burkholderia infections occur in the context of biologic warfare or bioterrorism.18,134

Chancroid and Granuloma Inguinale (Donovanosis)

Streptomycin has been used in the treatment of chancroid caused by Haemophilus ducreyi 1,2 and in the treatment of granuloma inguinale (Donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis );1,2 however, streptomycin is not included in current CDC guidelines for the treatment of these sexually transmitted diseases.131

Endocarditis

Enterococcal Endocarditis

Streptomycin is used in conjunction with other appropriate anti-infectives (ampicillin, penicillin G sodium, vancomycin) for the treatment of native or prosthetic valve endocarditis caused by Enterococcus (e.g., E. faecalis , E. faecium ).1,5,23,25,30 Enterococci usually are resistant to aminoglycosides alone and also are relatively resistant to penicillin G, ampicillin, and vancomycin.2,23,25 However, because antibacterial activity of the drugs may be additive or synergistic, regimens of gentamicin or streptomycin used concomitantly with ampicillin, penicillin G sodium, or vancomycin may be effective for the treatment of enterococcal endocarditis.2,23,25,30

For the treatment of native or prosthetic valve enterococcal endocarditis caused by strains susceptible to penicillin, vancomycin, and aminoglycosides, the American Heart Association (AHA) and IDSA recommend a regimen of IV ampicillin sodium or IV penicillin G sodium given in conjunction with either IV or IM gentamicin or IV† or IM streptomycin.25 Streptomycin usually is used only if the strains are gentamicin-resistant.25 For patients unable to tolerate penicillins, an alternative regimen is IV vancomycin given in conjunction with IV or IM gentamicin or IV† or IM streptomycin.25

Enterococcal isolates should routinely be tested for in vitro susceptibility to penicillin and vancomycin and for high-level resistance to gentamicin and streptomycin.24,25 (See Spectrum: In Vitro Susceptibility Testing in the Aminoglycosides General Statement 8:12.02.) The most appropriate regimen for the treatment of enterococcal endocarditis is selected based on results of in vitro susceptibility testing; treatment duration depends on whether native or prosthetic valves are involved and how long symptoms have been present prior to initiation of treatment.25 Gentamicin usually is the preferred aminoglycoside for the treatment of enterococcal endocarditis,5,25,30,31,32 in part because IV gentamicin may be better tolerated than IM streptomycin and because laboratory monitoring of gentamicin serum concentrations may be more readily available than laboratory monitoring of streptomycin concentrations.25,32 However, streptomycin may be effective for the treatment of enterococcal endocarditis caused by gentamicin-resistant strains since some, but not all, enterococci with high-level resistance to gentamicin are susceptible to streptomycin.2,5,23,25,30,31 Vancomycin should be used only in patients unable to tolerate ampicillin or penicillin G since regimens that include vancomycin and an aminoglycoside may be associated with an increased risk of ototoxicity and nephrotoxicity and may be less effective compared with regimens that include one of the β-lactams and an aminoglycoside.25 (See Drug Interactions: Neurotoxic, Ototoxic, or Nephrotoxic Drugs, in the Aminoglycosides General Statement 8:12.02.)

Endocarditis Caused by Viridans Streptococci or S. bovis

Streptomycin has been used concomitantly with penicillin G sodium for the treatment of endocarditis caused by viridans group streptococci.1 However, the AHA and IDSA recommend gentamicin as the aminoglycoside of choice for use in conjunction with penicillin G sodium or ceftriaxone for the treatment of native valve endocarditis caused by viridans group streptococci or Streptococcus bovis .24,25

For further information on treatment of enterococcal or streptococcal endocarditis, see the Aminoglycosides General Statement 8:12.02.

Plague

Treatment

Streptomycin is used for the treatment of plague caused by Yersinia pestis .1,5,19,38,132,134,135,136 Streptomycin generally has been considered the drug of choice for the treatment of bubonic, septicemia, and pneumonic plague;19,38,132,134,135,136 however, gentamicin also is considered a drug of choice since it may be as effective and is more readily available than streptomycin.19,33,34,38,132,134,136 Alternatives recommended when aminoglycosides are not used include doxycycline (or tetracycline), chloramphenicol, co-trimoxazole (may be less effective than other alternatives), or fluoroquinolones (ciprofloxacin, ofloxacin).19,33,38,132,134,135,136 Chloramphenicol generally is considered the drug of choice for the treatment of plague meningitis.19,38,134,136 Penicillins and other β-lactams are not recommended for the treatment of plague.38 Streptomycin-resistant Y. pestis (including multidrug-resistant strains) have been reported rarely.36,39 (See Resistance in the Aminoglycosides General Statement 8:12.02.)

Anti-infective regimens recommended for the treatment of naturally occurring or endemic bubonic, septicemic, or pneumonic plague also are recommended for the treatment of plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.19,132 These exposures would most likely result in primary pneumonic plague.132 Some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID, European Commission Task Force on Biological and Chemical Agent Threats [BICHAT]) recommend that treatment of plague in the context of biologic warfare or bioterrorism be initiated with a parenteral anti-infective such as streptomycin (or gentamicin) or, alternatively, doxycycline, ciprofloxacin, or chloramphenicol; an oral regimen (doxycycline, ciprofloxacin) may be substituted when the patient's condition improves or if parenteral therapy is unavailable.19,132,134

Prompt initiation of anti-infective therapy (within 18-24 hours of onset of symptoms) is essential in the treatment of pneumonic plague.132,134 When plague is suspected, appropriate anti-infectives should be initiated immediately and not delayed for laboratory confirmation.33

Prophylaxis

Postexposure prophylaxis with anti-infectives is recommended after high-risk exposures to plague, including close exposure to individuals with naturally occurring plague or laboratory exposure to viable Y. pestis .134,136,137 In the context of biologic warfare or bioterrorism, some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID) recommend that asymptomatic individuals with exposure to plague aerosol or asymptomatic individuals with household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague should receive postexposure anti-infective prophylaxis; however, any exposed individual who develops a temperature of 38.5°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease.132,134 An oral regimen of doxycycline or ciprofloxacin usually is recommended for such prophylaxis;132,134,136 although efficacy has not been established, co-trimoxazole has been recommended for prophylaxis in children younger than 8 years of age.136

Rat-bite Fever

Streptomycin is recommended as an alternative to penicillin G for the treatment of rat-bite fever† caused by Streptobacillus moniliformis or Spirillum minus .10,135,136 Although penicillin G usually is the drug of choice for these infections, a tetracycline (usually doxycycline) or streptomycin can be used10,135,136 in patients hypersensitive to penicillin.135,136

Tularemia

Treatment

Streptomycin is used in the treatment of tularemia caused by Francisella tularensis ,1,5,21,22,133,134,135,136 and generally is considered the drug of choice for this infection.5,21,22,133,134,135,136 However, gentamicin is more readily available and may be used as an alternative drug of choice when streptomycin is unavailable.21,22,133,134,136 Other alternatives for the treatment of tularemia include tetracyclines (doxycycline), chloramphenicol, or ciprofloxacin.21,22,133,134,135,136

Anti-infective regimens recommended for the treatment of naturally occurring or endemic tularemia also are recommended for the treatment of tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.21,133 However, the fact that a fully virulent streptomycin-resistant strain of F. tularensis was developed in the past for use in biologic warfare should be considered.133,134 Exposures to F. tularensis in the context of biologic warfare or bioterrorism would most likely result in inhalational tularemia with pleuropneumonitis, although the organism also can infect humans through the skin, mucous membranes, and GI tract.133

Prophylaxis

Postexposure prophylaxis with anti-infectives usually is not recommended after possible exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission of the disease is not known to occur.133,134 However, postexposure prophylaxis is recommended following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury).133 In the context of biologic warfare or bioterrorism, some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID, BICHAT) recommend that asymptomatic individuals with exposure to F. tularensis receive postexposure anti-infective prophylaxis; however, any individual who develops an otherwise unexplained fever or flu-like illness within 14 days of presumed exposure should promptly receive a parenteral anti-infective for treatment of the disease.21,133,134 Oral doxycycline (or oral tetracycline) or oral ciprofloxacin usually is recommended for postexposure prophylaxis following such exposures;133,134 streptomycin or gentamicin also have been recommended for postexposure prophylaxis of tularemia†.21

Urinary Tract, Respiratory Tract, and Other Infections

Streptomycin has been used for the treatment of urinary tract infections caused by susceptible Escherichia coli , Proteus , Klebsiella pneumoniae , Enterobacter , or E. faecalis .1 However, many strains of Enterobacteriaceae and Enterococcus are resistant to streptomycin alone2,135 and the drug should be used for these infections only when susceptibility has been demonstrated and other aminoglycosides or other appropriate anti-infectives are ineffective or contraindicated.5

Streptomycin has been used alone or in conjunction with other anti-infectives for the treatment of respiratory tract infections caused by susceptible Haemophilus influenzae or K. pneumoniae .1 Streptomycin also has been used in conjunction with other anti-infectives for the treatment of gram-negative bacillary bacteremia and meningitis or endocarditis caused by H. influenzae .1 However, streptomycin is not considered a drug of choice for these infections and should be used only when the causative organism is susceptible and other appropriate anti-infectives are ineffective or contraindicated.1

Reconstitution and Administration

Streptomycin sulfate is administered by IM injection.1 Although the commercially available preparation is for IM administration only,1 streptomycin sulfate has been administered by IV infusion†.2,5,107,108,109,110,127,128 Intrathecal† administration of streptomycin is not recommended.2

Patients should be under close clinical observation during streptomycin therapy because of the risk of ototoxicity and nephrotoxicity.1 (See Cautions in the Aminoglycosides General Statement 8:12.02.)

IM Injection

In adults, IM injections of streptomycin should be made deeply into a large muscle mass, preferably the upper outer quadrant of the buttock (i.e., gluteus maximus) or the mid-lateral thigh.1 In children, IM injections of the drug should preferably be given into the midlateral muscles of the thigh.1 To minimize the risk of sciatic nerve damage, the periphery of the upper outer quadrant of the gluteal region should be used in infants and small children only when necessary (e.g., in burn patients).1 IM injections should not be made into the lower or mid-third of the upper arm.1

As with all IM injections, aspiration is necessary to help avoid inadvertent injection into a blood vessel.1 To minimize irritation, IM injection sites should be alternated.1

Reconstitution

Streptomycin sulfate powder for injection containing 1 g of streptomycin should be reconstituted by adding 4.2, 3.2, or 1.8 mL of sterile water for injection to prepare a solution containing approximately 200, 250, or 400 mg, respectively, of streptomycin per mL.1

IV Infusion

For IV infusion† through a peripheral or central IV catheter in patients who could not tolerate IM injections of the drug, streptomycin solutions containing 12-15 mg/kg in 100 mL of 0.9% sodium chloride injection have been given by IV infusion over 30-60 minutes.107,108,109,110,127,128

Dosage

Dosage of streptomycin sulfate is expressed in terms of streptomycin.1

Like other aminoglycosides, dosage of streptomycin should individualized taking into consideration the patient's pretreatment body weight, renal status, severity of the infection, and susceptibility of the causative organism.1,2,5,6,35

Whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely, peak and trough serum concentrations of streptomycin should be monitored and dosage adjusted to maintain desired serum concentrations.5,6,25,35,114,115,116,117,118,119,124,125,126 (See Dosage and Administration: Dosage, in the Aminoglycosides General Statement 8:12.02.) A causal relationship between maintenance of certain peak or trough serum concentrations or other pharmacodynamic endpoints and clinical response or toxicity has not been established to date for streptomycin dosing regimens.114,116,120,121,122,123 However, suggested desirable peak and trough serum concentrations of streptomycin are 5-35 mcg/mL and less than 5-10 mcg/mL, respectively.5,25,35 Peak serum streptomycin concentrations greater than 40-50 mcg/mL may be associated with toxicity;2 some clinicians state that persistent concentrations greater than 20 mcg/mL should be avoided.2,6 For the treatment of enterococcal endocarditis, the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend that streptomycin dosage be adjusted to achieve 1-hour peak serum concentrations of 20-35 mcg/mL and trough concentrations less than 10 mcg/mL.25

Although streptomycin dosage regimens that involve once-daily (single-daily) dosing are recommended for the treatment of tuberculosis1,12,100 and brucellosis,14,15,16,134 once-daily streptomycin regimens are not usually recommended for other indications and should not be used for the treatment of enterococcal or streptococcal endocarditis.1,25

Adult Dosage

General Adult Dosage

If IM streptomycin is used concomitantly with other anti-infectives for the treatment of moderate to severe infections caused by susceptible gram-negative or gram-positive bacteria, the usual adult dosage is 1-2 g daily given in divided doses every 6-12 hours.1 Streptomycin dosage generally should not exceed 2 g daily.1

Active Tuberculosis

The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) state that the usual streptomycin dosage for use in conjunction with other antituberculosis agents for the treatment of active tuberculosis in adults is 15 mg/kg daily (up to 1 g) given IM or IV† as a single dose (usually 0.75-1 g daily) 5-7 times weekly for the first 2-4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.100

Because of an increased risk of toxicity, streptomycin dosage should be reduced in adults 60 years of age or older.1 The ATS, CDC, and IDSA recommend that adults older than 59 years of age receive a dosage of 10 mg/kg (up to 750 mg) daily for the treatment of tuberculosis.100

The manufacturer states that the usual adult dosage of IM streptomycin for the treatment of tuberculosis is 15 mg/kg (up to 1 g) given once daily.1 When intermittent antituberculosis therapy is used, the manufacturer recommends that adults receive 25-30 mg/kg (up to 1.5 g) IM 2-3 times weekly.1 In addition, the manufacturer states that the total streptomycin dosage over a course of therapy should not exceed 120 g unless there are no other therapeutic options.1

Other Mycobacterial Infections

For the treatment of pulmonary infections caused by Mycobacterium avium complex† (MAC) in adults not infected with human immunodeficiency virus infection (HIV), streptomycin is used in conjunction with a multiple-drug regimen of clarithromycin (or azithromycin), ethambutol, and either rifabutin or rifampin.11,26 Streptomycin is given 2 or 3 times weekly during the first 2-3 months of the multiple-drug regimen; a longer duration may be considered in those with very extensive disease or when other agents are poorly tolerated.26 Some HIV-negative adults with pulmonary MAC infections have received IM streptomycin in a dosage of 15 mg/kg 3 times weekly for 3 months in conjunction with clarithromycin (15 mg/kg daily), ethambutol (15 mg/kg daily), and rifampin (10 mg/kg daily) given for a median duration of 28 months.11

For the treatment of infections caused by M. kansasii †, streptomycin is used in conjunction with a multiple-drug regimen of isoniazid, rifampin, and ethambutol.26,28 Streptomycin has been given in a dosage of 1 g twice weekly during the first 2-3 months of the 12-month multiple-drug regimen.26,28

Brucellosis

When IM streptomycin is used in conjunction with doxycycline for the treatment of brucellosis, the usual adult dosage of streptomycin is 1 g or 15 mg/kg given once daily during the first 2-3 weeks of the doxycycline regimen (100 mg twice daily for at least 4-6 weeks).14,15,16,17,29,134 Adults older than 60 years of age have received IM streptomycin in a dosage of 1 g every other day for 3 weeks in conjunction with doxycycline.16

Endocarditis

For the treatment of native or prosthetic valve endocarditis caused by enterococci, streptomycin is used in conjunction with IV ampicillin sodium or IV penicillin G sodium.1,23,25 The manufacturer recommends that adults receive IM streptomycin in a dosage of 1 g twice daily for 2 weeks followed by 500 mg twice daily for an additional 4 weeks; the manufacturer states that ototoxicity may necessitate discontinuance of streptomycin prior to completion of the 6-week regimen.1 The American Heart Association (AHA) and IDSA recommend that adults receive IM or IV† streptomycin in a dosage of 15 mg/kg daily given in 2 divided doses in conjunction with IV ampicillin sodium (12 g daily in 6 equally divided doses) or IV penicillin G sodium (18-30 million units daily).25 In patients with native valve endocarditis, the AHA and IDSA recommend that treatment be continued for 4-6 weeks;25 although a 4-week regimen may be used in those who have had symptoms of infection for 3 months or less prior to initiation of treatment, a 6-week regimen is recommended for those who have had symptoms for longer than 3 months.25 In patients with a prosthetic valve or other prosthetic cardiac material, treatment should be continued for a minimum of 6 weeks.25 The AHA and IDSA state that once-daily streptomycin regimens should not be used for the treatment of enterococcal endocarditis.25

For the treatment of penicillin-susceptible streptococcal (viridans group) endocarditis (penicillin MIC of 0.1 mcg/mL or less), streptomycin is used in conjunction with penicillin G sodium.1 The manufacturer recommends that adults 60 years of age or younger receive IM streptomycin in a dosage of 1 g twice daily for 1 week followed by 500 mg twice daily for 1 week and that adults older than 60 years of age receive a dosage of 500 mg twice daily for 2 weeks.1

Plague

For the treatment of plague, including pneumonic plague that occurs as the result of exposure to Y. pestis in the context of biologic warfare or bioterrorism, the usual adult dosage of IM streptomycin is 1 g or 15 mg/kg (up to 1 g) twice daily.1,5,19,132,134 At least 10 days of therapy is recommended for the treatment of plague;1,132 some experts recommend a duration of at least 10-14 days.134

Tularemia

For the treatment of tularemia, the usual adult dosage of IM streptomycin is 1-2 g daily given in divided doses for 7-14 days and until the patient is afebrile for 5-7 days.1,5

For the treatment of tularemia that occurs as the result of exposure to F. tularensis in the context of biologic warfare or bioterrorism, the US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases (USAMRIID), and European Commission Task Force on Biological and Chemical Agent Threats (BICHAT) recommend that adults receive IM streptomycin in a dosage of 1 g twice daily for at least 10-14 days.21,133,134 If streptomycin is used for postexposure prophylaxis of tularemia†, a 14-day regimen has been recommended.21

Pediatric Dosage

General Pediatric Dosage

If IM streptomycin is used concomitantly with other anti-infectives for the treatment of moderate to severe infections caused by susceptible gram-negative or gram-positive bacteria, the usual dosage in children is 20-40 mg/kg daily given in divided doses every 6-12 hours.1 Particular care should be taken to avoid excessive dosage in children.1

A streptomycin dosage of 7.5 mg/kg given IM every 12 hours has been used in neonates.20

Active Tuberculosis

For the treatment of active tuberculosis in children younger than 15 years of age or weighing 40 kg or less, the ATS, CDC, and IDSA state that the usual dosage of IM or IV† streptomycin for use in conjunction with other antituberculosis agents is 20-40 mg/kg daily (up to 1 g).100 The ATS, CDC, and IDSA state that these pediatric patients also can receive IM or IV† streptomycin in an intermittent dosage regimen of 20 mg/kg twice weekly.100

For the treatment of active tuberculosis in pediatric patients 15 years of age or older or more than 40 kg, the ATS, CDC, and IDSA state that the usual dosage of IM or IV† streptomycin for use in conjunction with other antituberculosis agents is 15 mg/kg daily (up to 1 g) given as a single daily dose (usually 0.75-1 g daily) 5-7 times weekly for the first 2-4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.100

The manufacturer states that the usual pediatric dosage of streptomycin for the treatment of active tuberculosis is 20-40 mg/kg daily (up to 1 g) daily or 25-30 mg/kg (up to 1.5 g) 2-3 times weekly.1 In addition, the manufacturer states that the total streptomycin dosage in children over a course of therapy should not exceed 120 g unless there are no other therapeutic options.1

Brucellosis

When IM streptomycin is used in conjunction with other anti-infectives for the treatment of brucellosis in children, the manufacturer recommends 20-40 mg/kg in divided doses every 6-12 hours.1 Children 7 years of age or older have received IM streptomycin in a dosage of 1 g once daily (15 mg/kg daily in those weighing 50 kg or less) for 14 days in conjunction with oral doxycycline (100 mg twice daily [5 mg/kg in those weighing 40 kg or less) given for 45 days.17

Plague

For the treatment of plague, the usual dosage of IM streptomycin for children is 30 mg/kg daily (up to 2 g daily) given in 2 or 3 divided doses.132,134,136

Some clinicians recommend that for the treatment of plague, including pneumonic plague that occurs as the result of exposure to Yersinia pestis in the context of biologic warfare or bioterrorism, children should receive 15 mg/kg IM twice daily (maximum 2 g daily).19,132,134 At least 10 days of therapy is recommended for the treatment of plague;1,132 some experts recommend a duration of 10-14 days.134

Endocarditis

For the treatment of native or prosthetic valve endocarditis caused by enterococci, streptomycin is used in conjunction with IV ampicillin sodium or IV penicillin G sodium.1,25 The AHA and IDSA recommend that children receive IM or IV† streptomycin in a dosage of 20-30 mg/kg daily given in 2 divided doses.25 In patients with native valve endocarditis, the AHA and IDSA recommend that treatment be continued for 4-6 weeks;25 although a 4-week regimen may be used in those who have had symptoms of infection for 3 months or less prior to initiation of treatment, a 6-week regimen is recommended for those who have had symptoms for longer than 3 months.25 In patients with prosthetic valve or other prosthetic cardiac material, treatment should be continued for a minimum of 6 weeks.25 The AHA and IDSA state that once-daily streptomycin regimens should not be used for the treatment of enterococcal endocarditis.25

Tularemia

For the treatment of tularemia that occurs as the result of exposure to Francisella tularensis in the context of biologic warfare or bioterrorism, the US Working Group on Civilian Biodefense, USAMRIID, and BICHAT recommend that children receive IM streptomycin in a dosage of 15 mg/kg twice daily (maximum 2 g daily) for at least 10-14 days.21,133,134

Dosage in Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of streptomycin must be modified in response to serum concentrations of the drug and the degree of renal impairment.1,2,5,6,100 Because of the increased risk of ototoxicity and nephrotoxicity, streptomycin should be used with caution in patients with impaired renal function1,100 and serum concentrations of the drug monitored closely.100 The manufacturer recommends that peak serum concentrations of streptomycin should not exceed 20-25 mcg/mL in patients with renal impairment.1

Some clinicians recommend that adults with renal impairment receive an initial streptomycin loading dose of 15 mg/kg (approximately 1 g) of streptomycin.6 For subsequent therapy, these clinicians recommend that patients with creatinine clearances of 50-80 mL/minute receive 7.5 mg/kg once every 24 hours, those with creatinine clearances of 10-50 mL/minute receive 7.5 mg/kg once every 24-72 hours, and those with creatinine clearances less than 10 mL/minute receive 7.5 mg/kg once every 72-96 hours.6 In patients with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 25% of the initial loading dose at the end of each dialysis period.6

For the treatment of active tuberculosis in adults with renal impairment, the ATS, CDC, and IDSA recommend that usual doses be given at less frequent intervals since use of lower doses may reduce efficacy of the drug.100 These experts recommend that adults with renal impairment receive streptomycin in a dosage of 12-15 mg/kg daily given 2 or 3 times weekly.100 If the patient is receiving hemodialysis, the dose should be given after the procedure is finished.100 In addition, serum concentrations of the drug be should monitored to avoid toxicity.100

Pharmacokinetics

The pharmacokinetics of streptomycin are similar to those of the other aminoglycosides.5 In all studies described in the Pharmacokinetics section, streptomycin was administered as the sulfate salt; dosages and concentrations of the drug are expressed in terms of streptomycin.

Absorption

Streptomycin is not absorbed from the GI tract.2,5

Streptomycin is rapidly absorbed after IM injection.2,5 Following IM administration of a single 1-g dose of streptomycin in adults with normal renal function, peak serum streptomycin concentrations are attained within 1 hour and range from 25-50 mcg/mL; serum concentrations decrease 50% by 5-6 hours after the dose.1

In one study in premature infants, mean peak serum concentrations of about 29 mcg/mL were attained within 2 hours following IM administration of streptomycin 10-11 mg/kg; serum concentrations averaged 11 mcg/mL at 12 hours.7

Distribution

Streptomycin is rapidly distributed into most body tissues and fluids except the brain.1,2 Substantial amounts of the drug are attained in pleural fluid and tuberculous cavities, and small amounts are attained in saliva and sweat.1

Only very low concentrations of streptomycin are distributed into CSF, even in patients with meningitis.2,100

Streptomycin crosses the placenta; serum concentrations in cord blood are similar to maternal serum concentrations.1,2

Small amounts of streptomycin are distributed into milk.1

Elimination

The plasma elimination half-life of streptomycin usually is 2-3 hours in adults with normal renal function.2,6,8 The half-life has been reported to range from 4-10 hours in premature and newborn infants.7

The plasma elimination half-life of streptomycin has been reported to range from 50-111 hours in adults with severe renal impairment.2,6,8,9 In patients with impaired hepatic and renal function, the plasma elimination half-life may be more prolonged than in patients with renal impairment alone.6

In adults with normal renal function, approximately 29-90% of a single 600-mg IM dose of streptomycin is excreted unchanged by glomerular filtration within 24 hours1,2,8 with the major portion being excreted within the first 12 hours.2 Urine concentrations of streptomycin reach peak concentrations of 400 mcg/mL after a single 500-mg IM dose and 1 mg/mL or more following a single 1-g IM dose.2

Streptomycin is removed by hemodialysis.2,100

Chemistry and Stability

Chemistry

Streptomycin is an aminoglycoside antibiotic obtained from cultures of Streptomyces griseus .1,2,5 The drug is commercially available as the sulfate salt.1 Potency of streptomycin sulfate is expressed in terms of streptomycin.1 Streptomycin sulfate occurs as a white or practically white, hygroscopic powder that is odorless or has a faint odor.4 The drug is freely soluble in water and very slightly soluble in alcohol.4

Streptomycin sulfate is commercially available as a sterile lyophilized powder for injection without preservatives.1 Following reconstitution of the lyophilized powder with sterile water for injection, streptomycin sulfate solutions containing 200 mg of streptomycin per mL have a pH of 4.5-7.1,4

Stability

Streptomycin sulfate lyophilized powder for injection should be stored at 15-30°C and protected from light.1

Reconstituted solutions of streptomycin sulfate are stable for 1 week when stored at room temperature and protected from light;1 however, streptomycin sulfate powder for injection contains no preservatives and the possibility of microbial contamination of reconstituted solutions must be considered.3

Additional Information

For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, and dosage and administration of streptomycin, see the Aminoglycosides General Statement 8:12.02.

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