Drug class: Aminoglycosides
- Antimycobacterial Agents
VA class: AM300
CAS number: 3810-74-0

Introduction

Antibacterial and antituberculosis agent; aminoglycoside antibiotic obtained from cultures of Streptomyces griseus.^{1 2 5}

Uses for Streptomycin

Tuberculosis

Treatment of active (clinical) tuberculosis (TB) in conjunction with other antituberculosis agents.^{1 2 100 136}

Second-line agent used in multiple-drug regimens for relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.¹⁰⁰

Can be as effective as ethambutol when used in the initial phase of antituberculosis treatment and was previously included in recommendations for this treatment phase, but M. tuberculosis resistant to streptomycin has been reported with increasing frequency worldwide and the drug has become less useful.¹⁰⁰ ATS, CDC, and IDSA state that streptomycin is no longer considered interchangeable with ethambutol unless the strain is known to be susceptible to streptomycin or the patient is from a population in which streptomycin resistance is unlikely.¹⁰⁰

For initial treatment of active TB caused by drug-susceptible M. tuberculosis, recommended multiple-drug regimens consist of an initial intensive phase (2 months) and a continuation phase (4 or 7 months).^{100 136} Although the usual duration of treatment for drug-susceptible pulmonary and extrapulmonary TB (except disseminated infections and TB meningitis) is 6–9 months,^{100 136} ATS, CDC, and IDSA state that completion of treatment is determined more accurately by the total number of doses and should not be based solely on the duration of therapy.¹⁰⁰ A longer duration of treatment (e.g., 12–24 months) usually is necessary for infections caused by drug-resistant M. tuberculosis.^{100 136}

Patients with treatment failure or drug-resistant M. tuberculosis, including multidrug-resistant (MDR) TB (resistant to both isoniazid and rifampin) or extensively drug-resistant (XDR) TB (resistant to both isoniazid and rifampin and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial such as capreomycin, kanamycin, or amikacin), should be referred to or managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.¹⁰⁰

Mycobacterium avium Complex (MAC) Infections

Treatment of pulmonary infections caused by M. avium complex^{† [off-label]} (MAC) in conjunction with other antimycobacterials.^{11 26 28 136 c d}

For initial treatment of nodular/bronchiectatic pulmonary disease caused by macrolide-susceptible MAC, ATS and IDSA recommend a 3-times weekly regimen of clarithromycin (or azithromycin), ethambutol, and rifampin in most patients.²⁶ For initial treatment of fibrocavitary or severe nodular/bronchiectatic pulmonary disease caused by macrolide-susceptible MAC, ATS and IDSA recommend a daily regimen of clarithromycin (or azithromycin), ethambutol, and rifampin (or rifabutin) and state that consideration can be given to adding amikacin or streptomycin during the first 2–3 months of treatment for extensive (especially fibrocavitary) disease or when previous therapy has failed.²⁶

Not included in current guidelines for the treatment of disseminated MAC infections, including in HIV-infected individuals.^{26 27}

Treatment of MAC infections is complicated and should be directed by clinicians familiar with mycobacterial diseases; consultation with a specialist is particularly important when the patient cannot tolerate first-line drugs or when the infection has not responded to prior therapy or is caused by macrolide-resistant MAC.²⁶

Mycobacterium kansasii and Other Mycobacterial Infections

Treatment of M. kansasii^{† [off-label]} infections in conjunction with other antimycobacterials (e.g., isoniazid, rifampin, ethambutol).^{26 28 135} ATS and IDSA recommend a regimen of isoniazid, rifampin, and ethambutol for treatment of pulmonary or disseminated infections caused by rifampin-susceptible M. kansasii.²⁶ If rifampin-resistant M. kansasii are involved, ATS and IDSA recommend a 3-drug regimen based on results of in vitro susceptibility testing, including clarithromycin (or azithromycin), moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.²⁶ A regimen of isoniazid, ethambutol, sulfamethoxazole, and pyridoxine with streptomycin during the initial 2–3 months of treatment has been used.²⁶

Treatment of infections caused by M. xenopi^{† [off-label]} in conjunction with other antimycobacterials.²⁶ Optimum regimens not established; in vivo response may not correlate with in vitro susceptibility.²⁶ ATS and IDSA state that a regimen of clarithromycin, rifampin, and ethambutol generally has been used, although rate of relapse is high.²⁶ A regimen of isoniazid, rifampin (or rifabutin), ethambutol, and clarithromycin (without or without streptomycin during initial treatment) also has been suggested.²⁶

Brucellosis

Treatment of brucellosis caused by Brucella melitensis.^{13 14 15 17 134 135 136} Tetracyclines generally considered the drugs of choice; 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 not recommended.^{14 29 134 136}

Burkholderia Infections

Treatment of glanders^{† [off-label]} caused by Burkholderia mallei; used in conjunction with a tetracycline or chloramphenicol.¹³⁵

Chancroid

Has been used for treatment of chancroid caused by Haemophilus ducreyi,² but streptomycin is not included in current CDC guidelines for treatment of the disease.¹³¹

Granuloma Inguinale (Donovanosis)

Has been used for treatment of granuloma inguinale (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis),^{1 2} but streptomycin is not included in current CDC guidelines for treatment of the disease.¹³¹

Endocarditis

Treatment of native or prosthetic valve endocarditis caused by Enterococcus (e.g., E. faecalis, E. faecium); ^{1 5 23 25 30} used as an adjunct to other appropriate anti-infectives (ampicillin, penicillin G sodium, or vancomycin).^{2 23 25 30} Enterococci usually are resistant to aminoglycosides alone and also are relatively resistant to penicillin G, ampicillin, and vancomycin;^{2 23 25} 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 treatment of enterococcal endocarditis.^{2 23 25 30} 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} Gentamicin usually is the preferred aminoglycoside for treatment of enterococcal endocarditis,^{5 25 30 31 32} but streptomycin may be effective for treatment of gentamicin-resistant strains.^{2 5 23 25 30 31}

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

Treatment of endocarditis caused by susceptible Haemophilus influenzae; used in conjunction with another suitable anti-infective.¹ Not a drug of choice; use only if in vitro susceptibility has been demonstrated and other anti-infectives are ineffective or contraindicated.¹

Plague

Treatment of plague caused by Yersinia pestis, including naturally occurring or endemic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.^{1 5 19 38 132 134 135 136}

Regimen of choice is streptomycin or gentamicin (with or without a tetracycline);^{19 38 132 134 135 136} alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol.^{132 134} For plague meningitis, some experts recommend that chloramphenicol be included in the treatment regimen.¹³⁴

Rat-bite Fever

Alternative for treatment of rat-bite fever^{† [off-label]} caused by Streptobacillus moniliformis or Spirillum minus^{10 135 136} in patients hypersensitive to penicillin.¹³⁶

Tularemia

Drug of choice^{5 21 134 135} for treatment of tularemia caused by Francisella tularensis,^{1 5 21 22 133 134 135 136} including naturally occurring or endemic tularemia^{21 133} or tularemia that occurs as the result of biologic warfare or bioterrorism.^{21 133 134}

Postexposure prophylaxis of tularemia^†.²¹ Oral doxycycline, oral tetracycline, or oral ciprofloxacin usually recommended following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism.^{133 134} Postexposure prophylaxis usually not recommended after 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 does not occur.¹³⁴

Urinary Tract, Respiratory Tract, and Other Infections

Treatment of urinary tract infections caused by susceptible Enterobacter aerogenes, Escherichia coli, Proteus, Klebsiella pneumoniae, or E. faecalis.¹ Many strains of Enterobacteriaceae and Enterococcus are resistant to streptomycin alone;^{2 135} use only if in vitro susceptibility has been demonstrated and other aminoglycosides or other anti-infectives are ineffective or contraindicated.⁵

Treatment of respiratory tract infections caused by susceptible H. influenzae or K. pneumoniae, including pneumonia caused by K. pneumoniae; used in conjunction with another suitable anti-infective.¹ Not a drug of choice; use only if in vitro susceptibility has been demonstrated and other anti-infectives are ineffective or contraindicated.¹

Treatment of gram-negative bacillary bacteremia caused by susceptible gram-negative bacteria; used in conjunction with another suitable anti-infective.¹ Not a drug of choice; use only if in vitro susceptibility has been demonstrated and other anti-infectives are ineffective or contraindicated.¹

Treatment of meningeal infections caused by susceptible H. influenzae; used in conjunction with another suitable anti-infective.¹ Not a drug of choice; use only if in vitro susceptibility has been demonstrated and other anti-infectives are ineffective or contraindicated.¹

Streptomycin Dosage and Administration

Administration

Administer by IM injection¹ or IV infusion^†.^{2 5 107 108 109 110 127 128}

Intrathecal administration not recommended.²

IM Administration

Administer IM deeply into a large muscle mass (e.g., gluteus maximus or mid-lateral thigh) after aspiration to avoid possible inadvertent intravascular injection.¹

In children, administer into the midlateral muscles of the thigh.¹

In infants and small children, to minimize the risk of sciatic nerve damage, do not use the periphery of the upper outer quadrant of the gluteal region unless necessary (e.g., burn patients).¹

Do not administer IM injections into the lower or mid-third of the upper arm.¹ Use deltoid area only if well developed in certain adults and older children; inject cautiously to avoid radial nerve injury.¹

To minimize irritation, alternate IM injection sites.¹

Reconstitution

Reconstitute vial containing 1 g streptomycin powder with 4.2, 3.2, or 1.8 mL of sterile water for injection to provide a solution containing approximately 200, 250, or 400 mg/mL, respectively.¹

IV Infusion†

For drug compatibility information, see Compatibility under Stability.

IV infusion^† through a peripheral or central IV catheter has been used for patients who could not tolerate IM injection.^{107 108 109 110 127 128}

Reconstitution and Dilution

Reconstitute vial containing 1 g streptomycin powder with 4.2, 3.2, or 1.8 mL of sterile water for injection to provide a solution containing approximately 200, 250, or 400 mg/mL, respectively.¹

Following reconstitution, dilute in 100 mL of 0.9% sodium chloride injection.^{107 108 109 110 127 128}

Rate of Administration

30–60 minutes.^{107 108 109 110 127 128}

Dosage

Available as streptomycin sulfate; dosage expressed in terms of streptomycin.¹

Use lowest possible dosage for shortest duration of therapy.^b

Base dosage on patient's pretreatment body weight and renal status.^{1 2 5 6 35}

Many clinicians recommend that dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data, susceptibility of the causative organism, severity of the infection, and the patient's immune and clinical status.^{1 2 5 6 35} Because of potential toxicity, fixed-dosage recommendations not based on patient weight or serum drug concentrations are not advised.^b

Determine peak and trough serum streptomycin concentrations periodically during therapy. ^b Adjust dosage to maintain desired serum concentrations 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.^{5 6 25 35 114 115 116 117 118 119 124 125 126}

In general, desirable peak streptomycin concentrations (30–60 minutes following IM injection or 15–30 minutes after completion of an IV infusion^†)^b during parenteral therapy are 5–35 mcg/mL and trough concentrations (just prior to the next dose) should not be >5–10 mcg/mL.^{5 25 35} A casual relationship between maintenance of certain peak and trough serum concentrations and clinical response or toxicity is not established for streptomycin dosage regimens.^{114 116 120 121 122 123} However, some evidence suggests that an increased risk of toxicity may be associated with prolonged peak concentrations >40–50 mcg/mL.² Some clinicians recommend avoiding persistent concentrations >20 mcg/mL.^{2 6} For the treatment of enterococcal endocarditis, AHA and IDSA recommend adjusting dosage to achieve 1-hour peak serum concentrations of 20–35 mcg/mL and trough concentrations <10 mcg/mL.²⁵ Do not exceed peak serum concentrations of 20–25 mcg/mL in patients with renal impairment.¹

Once-daily administration of streptomycin is recommended for the treatment of active (clinical) TB^{1 12 100} and brucellosis;^{14 15 16 134} not usually recommended for other indications.^{1 25} Do not use once-daily regimens for treatment of enterococcal or streptococcal endocarditis.^{1 25}

Pediatric Patients

General Pediatric Dosage for Neonates

IM

7.5 mg/kg every 12 hours.²⁰

General Dosage for Infants and Children

IM

20–40 mg/kg daily given in divided doses every 6–12 hours.¹

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

IM or IV^†

Children <15 years of age or weighing ≤40 kg: ATS, CDC and IDSA recommend 20–40 mg/kg daily (up to 1 g).¹⁰⁰ Alternatively, 20 mg/kg twice weekly.¹⁰⁰ Used in conjunction with other antituberculosis agents.¹⁰⁰

Children ≥15 years of age or weighing >40 kg: ATS, CDC and IDSA recommend 15 mg/kg (up to 1 g) given as a single dose (usually 0.75–1 g) 5–7 times weekly for the first 2–4 months or until culture conversion;¹⁰⁰ dosage can then be reduced to 15 mg/kg daily (up to 1 g) given as a single dose 2–3 times weekly.¹⁰⁰ Used in conjunction with other antituberculosis agents.¹⁰⁰

Manufacturer recommends 20–40 mg/kg (up to 1 g) daily or 25–30 mg/kg (up to 1.5 g) 2–3 times weekly.¹

Brucellosis

IM

20–40 mg/kg daily given in divided doses every 6–12 hours; used in conjunction with other anti-infectives.¹

Children ≥7 years of age: Some clinicians recommend 1 g once daily (15 mg/kg in those weighing ≤50 kg) for 14 days in conjunction with oral doxycycline (100 mg twice daily [5 mg/kg in those weighing ≤40 kg]) for 45 days.¹⁷

Endocarditis

Treatment of Enterococcal Endocarditis

IM or IV^†

20–30 mg/kg daily given in 2 divided doses in conjunction with other anti-infectives.²⁵

Usually used in conjunction with IV ampicillin or IV penicillin G.²⁵ For native valve enterococcal endocarditis caused by strains susceptible to penicillin and streptomycin, usual duration of therapy is 4–6 weeks although a 4-week regimen may be used in those who have had symptoms of infection for ≤3 months prior to initiation of treatment.²⁵ For prosthetic valve or other prosthetic cardiac material, a minimum of 6 weeks is recommended.²⁵

When used in conjunction with vancomycin in those unable to receive a β-lactam, usual duration is 6 weeks.²⁵

Plague

Treatment of Plague

IM

30 mg/kg daily (up to 2 g daily) given in 2–3 divided doses for at least 10–14 days.^{19 132 134 136}

Tularemia

Treatment of Tularemia

IM

15 mg/kg twice daily (up to 2 g daily) for at least 10–14 days.^{21 133 134}

Adults

General Adult Dosage

IM

1–2 g daily given in divided doses every 6–12 hours.¹ Used concomitantly with other anti-infectives.¹

IV Infusion†

12–15 mg/kg given over 30–60 minutes.^{107 108 109 110 127}

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

IM or IV^†

ATS, CDC and IDSA recommend 15 mg/kg (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;¹⁰⁰ dosage can then be reduced to 15 mg/kg (up to 1 g) given as a single dose 2–3 times weekly.¹⁰⁰

Manufacturer recommends 15 mg/kg (up to 1 g) given once daily or 25–30 mg/kg (up to 1.5 g) 2–3 times weekly.¹

Mycobacterium Avium Complex (MAC) Infections†

Treatment of Pulmonary MAC Infections†

IM

15 mg/kg 3 times weekly has been given for the initial 3 months of a multiple-drug regimen of clarithromycin, ethambutol, and rifampin; the other drugs were continued for a median duration of 28 months.¹¹ Alternatively, 1 g 3 times weekly has been given for the initial 2–6 months of a regimen of clarithromycin, ethambutol, and rifampin; the other drugs were continued for at least 12 months.^c

When a multiple-drug regimen (e.g., clarithromycin [or azithromycin], ethambutol, rifampin) is used for treatment of extensive (especially fibrocavitary) disease or when previous therapy has failed, ATS and IDSA state that consideration can be given to adding streptomycin during the initial 2–3 months of treatment; streptomycin may need to be continued for a longer duration if disease is extensive or the other agents are poorly tolerated.²⁶ A dosage of 25 mg/kg 3 times weekly during the initial 3 months has been recommended, but this dosage may be impractical for IM administration and may not be tolerated.²⁶ For older patients with nodular/bronchiectatic disease or patients who require long-term streptomycin therapy (e.g., ≥6 months), ATS and IDSA state that a dosage of 8–10 mg/kg given 2 or 3 times weekly may be necessary (maximum 500 mg in those ≥50 years of age).²⁶

Mycobacterium kansasii and Other Mycobacterial Infections†

Treatment of M. kansasii Infections†

IM

Has been given twice weekly for the initial 3 months of a multiple-drug regimen of isoniazid, rifampin, and ethambutol; the other drugs were continued for 12 months.²⁸

Brucellosis

IM

1 g (or 15 mg/kg) once daily for the initial 2–3 weeks of oral doxycycline treatment given for ≥4–6 weeks.^{14 15 16 17 29 134}

Endocarditis

Treatment of Enterococcal Endocarditis

IM or IV^†

Manufacturer recommends 1 g twice daily for 2 weeks, then 500 mg twice daily for 4 more weeks in conjunction with other anti-infectives.¹ Manufacturer states ototoxicity may require termination prior to completion of the 6-week regimen.¹

AHA and IDSA recommend 15 mg/kg daily given in 2 divided doses in conjunction with other anti-infectives.²⁵

Usually used in conjunction with IV ampicillin or IV penicillin G.^{1 23 25} For native valve enterococcal endocarditis caused by strains susceptible to penicillin and streptomycin, usual duration of therapy is 4–6 weeks although a 4-week regimen may be used in those who have had symptoms of infection for ≤3 months prior to initiation of treatment.²⁵ For prosthetic valve or other prosthetic cardiac material, a minimum of 6 weeks is recommended.²⁵

When used in conjunction with vancomycin in those unable to receive a β-lactam, usual duration is 6 weeks.²⁵

Treatment of Endocarditis Caused by Penicillin-Susceptible Viridans Streptococci

IM

Adults ≤60 years of age: 1 g twice daily for 1 week, then 500 mg twice daily for 1 week.¹ Used in conjunction with penicillin G sodium.¹

Adults >60 years of age: 500 mg twice daily for 2 weeks.¹ Used in conjunction with penicillin G sodium.¹

Plague

Treatment of Plague

IM

1 g or 15 mg/kg (up to 1 g) twice daily for at least 10–14 days.^{1 5 19 132 134}

Tularemia

Treatment of Tularemia

IM

1–2 g daily given in divided doses for 7–14 days and until afebrile for 5–7 days.^{1 5}

Treatment of Tularemia Occurring in the Context of Biologic Warfare or Bioterrorism

IM

1 g twice daily for at least 10–14 days.^{21 133 134}

Postexposure Prophylaxis Following High-risk Exposure†

IM

Administer for at least 14 days.²¹

Prescribing Limits

Pediatric Patients

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

IM or IV^†

Maximum 1 g daily recommended by ATS, CDC and IDSA.¹⁰⁰

Manufacturer recommends maximum 1 g daily for once-daily regimens or maximum 1.5 g per dose in 2- or 3-times weekly regimens.¹

Manufacturer states maximum total dosage over course of therapy is ≤120 g unless no other therapeutic options are available.¹

Plague

IM

Maximum 2 g daily.^{132 134 136}

Tularemia

IM

Maximum 2 g daily.^{21 133 134}

Adults

General Adult Dosage

Maximum 2 g daily.¹

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

IM or IV

ATS, CDC and IDSA recommend maximum 1 g per dose in once-daily or 2- or 3-times weekly regimens in adults ≤59 years of age and maximum 750 mg per dose in once-daily or 2- or 3-times weekly regimens in those >59 years of age.¹⁰⁰

Manufacturer recommends maximum 1 g per dose in once-daily regimens or maximum 1.5 g per dose in 2- or 3-times weekly regimens.¹

Manufacturer states maximum total dosage over course of therapy is ≤120 g unless no other therapeutic options are available.¹

Plague

IM

Maximum 1 g daily.^{1 5 19 132 134}

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

Dosage adjustments necessary in patients with renal impairment.^{1 2 5 6 100} Whenever possible, monitor serum streptomycin concentrations, especially in patients with changing renal function.¹⁰⁰

Various methods have been used to determine aminoglycoside dosage for patients with renal impairment and there is wide variation in dosage recommendations for these patients.^b Some clinicians recommend an initial loading dose of 15 mg/kg (approximately 1 g).⁶ Then, for Cl_cr50–80 mL/minute, give 7.5 mg/kg once every 24 hours; for Cl_cr10–50 mL/minute, give 7.5 mg/kg once every 24–72 hours; for Cl_cr<10 mL/minute, give 7.5 mg/kg once every 72–96 hours.⁶

Dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.^b 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 treatment of active TB, ATS, CDC, and IDSA recommend 12–15 mg/kg daily given 2–3 times weekly.¹⁰⁰ Give usual doses at less frequent intervals; use of lower doses may reduce efficacy.¹⁰⁰ Give dose after hemodialysis is finished.¹⁰⁰ Monitor serum streptomycin concentrations in dialysis patients and adjust dosage to maintain desired concentrations.¹⁰⁰

Consult specialized references for specific information on dosage for patients with renal impairment.^a

Geriatric Patients

Treatment of active TB in adults >59 years of age: ATS, CDC, and IDSA recommend 10 mg/kg (maximum 750 mg) daily.¹⁰⁰

Treatment of brucellosis in adults >60 years of age: 1 g every other day for 3 weeks in conjunction with doxycycline.¹⁶

Treatment of endocarditis caused by penicillin-susceptible viridans streptococci in adults >60 years of age: 500 mg twice daily for 2 weeks.¹

Cautions for Streptomycin

Contraindications

• History of hypersensitivity or serious toxic reactions to streptomycin or other aminoglycosides.¹

Warnings/Precautions

Warnings

Ototoxicity

May cause both vestibular and auditory ototoxicity; risk is directly proportional to dose, duration, patient age, level of renal function, and amount of underlying auditory dysfunction.¹

Perform baseline and periodic caloric stimulation tests and audiometric tests if streptomycin therapy is prolonged.¹

Ototoxic effects may be potentiated by concomitant administration of diuretics (e.g., ethacrynic acid, mannitol, furosemide).¹ (See Interactions.)

Vestibular damage is more likely than cochlear toxicity.¹ Headache, nausea, vomiting, or disequilibrium may be symptoms of vestibular damage; loss of high frequency hearing may be a symptom of early cochlear damage.¹

Appropriate monitoring and early discontinuance of streptomycin may permit recovery prior to irreversible damage to the sensorineural cells.¹ If detected early, gross vestibular symptoms (except for relative inability to walk in total darkness or on very rough terrain) usually disappear 2–3 months after streptomycin discontinued.¹

Perform audiometric testing and/or discontinue streptomycin if patient has tinnitus, roaring noises, or a sense of fullness in the ears.¹

Vestibular dysfunction is cumulatively related to the total daily dose; 1.8–2 g given daily is likely to produce symptoms within 4 weeks in a large percentage of patients, especially in the elderly or patients with impaired renal function.¹

May cause fetal ototoxicity if administered to pregnant women.¹ (See Pregnancy under Cautions.) Advise patient of potential hazard to the fetus if she becomes pregnant while taking streptomycin.¹

Sensitivity Reactions

Hypersensitivity

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with aminoglycosides.^{f g h i j k l o p q r t v}

Skin sensitivity reactions possible; handle streptomycin carefully.¹

Cross-sensitivity

Cross-sensitivity occurs among the aminoglycosides.¹

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of streptomycin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.¹

Precautions Related to Treatment of Tuberculosis

Should not be used alone for the treatment of active TB; must be used in conjunction with other antituberculosis agents.^{1 2 100 136}

If added as a new drug to a regimen in patients experiencing treatment failure who have proven or suspected drug-resistant TB, 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

Compliance with the full course of antituberculosis therapy and all drugs included in the multiple-drug regimen is critical.¹⁰⁰ Missed doses increase the risk of treatment failure and increase the risk that M. tuberculosis will develop resistance to the antituberculosis regimen.¹⁰⁰

To ensure compliance, ATS, CDC, IDSA, and AAP recommend that directly observed (supervised) therapy (DOT) be used for treatment of active (clinical) TB whenever possible, especially when intermittent regimens are used, when the patient is immunocompromised or infected with HIV, or when drug-resistant M. tuberculosis is involved.^{100 136}

Precautions Related to Treatment of Sexually Transmitted Diseases

When treating sexually transmitted diseases (i.e., granuloma inguinale, chancroid), perform suitable laboratory procedures (e.g., dark field examination) before starting treatment if concomitant syphilis is suspected; repeat serologic tests monthly for ≥4 months.¹

Specific Populations

Pregnancy

Category D.¹

Possibility of fetal harm if administered to a pregnant woman.^{1 2} Congenital deafness reported when streptomycin was used during pregnancy.^{2 100}

Lactation

Distributed into milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Avoid excessive dosage in children.¹

CNS depression (e.g., stupor, flaccidity, coma, deep respiratory depression) reported in very young infants receiving streptomycin dosage exceeding the recommended maximum dosage.¹

Geriatric Use

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.¹ Increased risk of ototoxicity and nephrotoxicity.¹

When assessing renal function in geriatric patients, Cl_cr may be more useful than determining BUN or S_cr.^{f g h i m n p q r s t}

Renal Impairment

Risk of neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) is greater in patients with renal impairment than in other patients.¹

Nephrotoxicity may occur.¹

Dosage adjustments necessary based on degree of renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

In severely uremic patients, a single dose may produce high blood levels for several days; may result in ototoxicity.¹ Choose dosage with caution.¹

Alkalinization of the urine may minimize or prevent renal irritation during prolonged streptomycin therapy.¹

Common Adverse Effects

Vestibular ototoxicity (nausea, vomiting, vertigo), paresthesia of the face, rash, fever, urticaria, angioneurotic edema, eosinophilia.¹

Drug Interactions

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, cephalosporins, colistimethate/colistin, cisplatin, methoxyflurane, polymyxin B, vancomycin) may result in additive toxicity and should be avoided, if possible.^{1 b}

Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, do not give concurrently with potent diuretics such as ethacrynic acid, furosemide, or mannitol.^{1 b}

Specific Drugs and Laboratory Tests

Streptomycin Pharmacokinetics

Absorption

Bioavailability

Not absorbed from GI tract.^{2 5}

Rapidly absorbed following IM injection;^{2 5} peak serum concentrations attained within 1 hour.¹

Plasma Concentrations

Adults with normal renal function: A single IM injection of 1 g results in peak serum concentrations of 25–50 mcg/mL within 1 hour.¹

Premature neonates: A single IM injection of 10–11 mg/kg results in peak serum concentrations of about 29 mcg/mL within 2 hours.⁷

Special Populations

Plasma concentrations are higher in patients with renal impairment.^{2 6 8 9}

Distribution

Extent

Rapidly distributed into most body tissues and fluids,^{1 2} including pleural fluid, tuberculous cavities,¹ and caseous tissue.^b Distributed in low concentrations in saliva and sweat.¹ Does not penetrate thick-walled abscesses or ocular tissue.^b

Very low concentrations distributed into CSF, even in meningitis patients.^{2 100}

Crosses the placenta and is distributed into cord blood.^{1 2}

Distributed into milk.^{1 2}

Elimination

Elimination Route

Excreted unchanged principally in urine (29–90% of an IM dose) by glomerular filtration.^{1 2 8}

Removed by hemodialysis.^{2 100}

Half-life

Adults with normal renal function: 2–3 hours.^{2 6 8}

Premature infants and neonates: 4–10 hours.⁷

Special Populations

Adults with severe renal impairment: Half-life 50–111 hours.^{2 6 8 9}

Impaired hepatic and impaired renal function: Half-life may be more prolonged than with renal impairment alone.⁶

Stability

Storage

Parenteral

Powder for Injection

15–30°C; protect from light.¹

Protect reconstituted solution from light.¹ Manufacturer states reconstituted solution may be stored at room temperature for up to 1 week.¹ However, consider possibility of microbial contamination since preparation contains no preservatives.³

Compatibility

Drug Compatibility

Actions and Spectrum

• Usually bactericidal.^{1 b}

• Inhibits protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.^b

• In vitro spectrum of activity includes many gram-negative aerobic bacteria, some mycobacteria, and some aerobic gram-positive bacteria.^b Inactive against fungi, viruses, and most anaerobic bacteria.^b

• Gram-positive aerobes: Active in vitro against Erysipelothrix, Enterococcus faecalis, Nocardia,^b and Streptococcus viridans.¹

• Gram-negative aerobes: Active in vitro and in clinical infections against Brucella,¹ Enterobacter aerogenes,¹ Escherichia coli,^{1 b} Francisella tularensis,^{1 b} Haemophilus ducreyi,^{1 b} H. influenzae,^{1 b} Klebsiella granulomatis (formerly Calymmatobacterium granulomatis),^{1 b} Klebsiella pneumoniae,¹ Pasteurella multocida,^b Proteus,^{1 b} and Yersinia pestis.¹

• Mycobacteria: Active against Mycobacterium tuberculosis,^{1 w} M. bovis,^u M. genavense,²⁶ and some strains of M. avium complex (MAC),^{u x y} M. kansasii,^{u x aa bb} M. malmoense,^x M. marinum,^{26 u x} M. szulgai,^x and M. ulcerans.^{u z}

• Partial cross-resistance occurs between streptomycin and other aminoglycosides.^b

• Resistant strains of Y. pestis reported, including some multidrug-resistant strains.^{cc dd}

• Resistant strains of M. avium complex (MAC) with intermediate or high-level in vitro resistance reported.^y

Advice to Patients

• Advise patients that antibacterials (including streptomycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹

• Advise patients being treated for TB that poor compliance with antituberculosis regimens can result in treatment failure and development of drug-resistant TB, which can be life-threatening and lead to other serious health risks.¹⁰⁰

• Importance of completing full course of therapy, even if feeling better after a few days.¹

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with streptomycin or other antibacterials in the future.¹

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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