Streptomycin

Frequency Not Defined

Hypotension

Neurotoxicity

Drowsiness

Headache

Drug fever

Paresthesia

Skin rash

Nausea

Vomiting

Eosinophilia

Anemia

Arthralgia

Weakness

Tremor

Ototoxicity (auditory)

Ototoxicity (vestibular)

Nephrotoxicity

Difficulty in breathing

Ototoxicity: Both vestibular and auditory dysfunction can follow the administration of streptomycin. The degree of impairment is directly proportional to the dose and duration of streptomycin administration, to the age of the patient, to the level of renal function and to the amount of underlying existing auditory dysfunction. The ototoxic effects of the aminoglycosides, including streptomycin, are potentiated by the co-administration of ethacrynic acid, mannitol, furosemide and possibly other diuretics.

The vestibulotoxic potential of streptomycin exceeds that of its capacity for cochlear toxicity. Vestibular damage is heralded by headache, nausea, vomiting and disequilibrium. Early cochlear injury is demonstrated by the loss of high frequency hearing. Appropriate monitoring and early discontinuation of the drug may permit recovery prior to irreversible damage to the sensorineural cells.

Pregnancy: Streptomycin can cause fetal harm when administered to a pregnant woman. Because 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.

• If you have an allergy to streptomycin or any other part of streptomycin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• If you need to store streptomycin at home, talk with your doctor, nurse, or pharmacist about how to store it.

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 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 

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 diameter2:

Acceptable Control Ranges 

Interpretive Criteria for Agents of Bioterrorism 

Streptomycin is indicated for the treatment of individuals with moderate to severe infections caused by susceptibile strains of microorganisms in the specific conditions listed below:

1. Mycobacterium tuberculosis: The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Center for Disease Control recommend that either Streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. In the past when the national rate of primary drug resistance to isoniazid was known to be less than 4% and was either stable or declining, therapy with two and three drug regimens was considered adequate. If community rates of INH resistance are currently less than 4%, an initial treatment regimen 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.

2. 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.

   1. Pasteurella pestis (plague),

   2. Francisella tularensis (tularemia),

   3. Brucella,

   4. Calymmatobacterium granulomatis (donovanosis, granuloma inguinale),

   5. H. ducreyi (chancroid),

   6. H. influenzae (in respiratory, endocardial, and meningeal infections-concomitantly with another antibacterial agent),

   7. K. pneumoniae pneumonia (concomitantly with another antibacterial agent),

   8. E.coli, Proteus, A. aerogenes, K. pneumoniae, and Enterococcus faecalis in urinary tract infections,

   9. Streptococcus viridans, Enterococcus faecalis (in endocardial infections -concomitantly with penicillin),

   10. 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.

• Antibiotic, Aminoglycoside
• Antitubercular Agent

Note: Manufacturer’s labeling states for IM administration only, however, IV administration (off-label route) has been described (Morris 1994; Peloquin 1992; Tanoira 2014).

Usual dosage range: IM: 15 to 30 mg/kg/day or 1 to 2 g daily

Indication-specific dosing:

Brucellosis: IM: 1 g daily in 2 to 4 divided doses for 14 to 21 days (with doxycycline) (Skalsky 2008)

Endocarditis:

Enterococcal:

Manufacturer’s labeling: IM: 1 g every 12 hours for 2 weeks, followed by 500 mg every 12 hours for 4 weeks in combination with penicillin

Alternate dosing (susceptible to penicillin and streptomycin/resistant to gentamicin): Native or prosthetic valve: IM, IV: 15 mg/kg/day in divided doses every 12 hours in combination with ampicillin or penicillin; Duration of therapy: 4 weeks (native valve and symptoms present <3 months); ≥6 weeks (native valve and symptoms present ≥3 months or prosthetic valve) (AHA [Baddour 2015])

Streptococcal:Manufacturer’s labeling: IM: 1 g every 12 hours for 1 week, followed by 500 mg every 12 hours for 1 week in combination with penicillin.

Mycobacterium avium complex (MAC) (off-label use): IM: Adjunct therapy (with macrolide, rifamycin, and ethambutol): 8 to 25 mg/kg 2 to 3 times weekly for first 2 to 3 months for severe disease (maximum single dose for age >50 years: 500 mg) (Griffith 2007)

Mycobacterium avium complex (MAC) disease, disseminated in HIV-infected patients (off-label use): IM, IV: 1 g daily as optional adjunct therapy with ethambutol (plus clarithromycin or azithromycin) (HHS [OI adult 2015])

Mycobacterium kansasii disease (rifampin-resistant) (off-label use): IM: 750 mg to 1 g daily (as part of a three-drug regimen based on susceptibilities) (Campbell 2000; Griffith 2007)

Mycobacterium ulcerans (Buruli ulcers) (off-label use): IM: 15 mg/kg once daily (maximum dose: 1 g) in combination with rifampin for 8 weeks or in combination with rifampin for 4 weeks, followed by 4 weeks of rifampin and clarithromycin (WHO 2012)

Plague: IM:

Manufacturer’s labeling: 1 g twice daily for a minimum of 10 days.

Alternate dosing: 30 mg/kg/day (maximum dose: 2 g) divided every 12 hours until the patient is afebrile for at least 2 to 3 days. Note: Full course is considered 10 days (CDC 2014; WHO 2009).

Tuberculosis:

Manufacturer’s labeling: IM:

Daily therapy: 15 mg/kg/day (maximum: 1 g)

Directly observed therapy (DOT), twice weekly: 25 to 30 mg/kg (maximum: 1.5 g)

Directly observed therapy (DOT), 3 times weekly: 25 to 30 mg/kg (maximum: 1.5 g)

Alternate dosing: IM, IV: 15 mg/kg (maximum dose: 1 g) once daily for 5 to 7 days per week for 2 to 4 months, followed by 15 mg/kg (maximum dose: 1 g) 2 to 3 times weekly (ATS 2003)

Tularemia: IM:

Manufacturer’s labeling: 1 to 2 g daily in divided doses every 12 hours for 7 to 14 days until the patients is afebrile for 5 to 7 days

Alternative regimen: 2 g daily in 2 divided doses for ≥10 days (WHO 2007)

IM: Inject deep IM into large muscle mass; midlateral thigh muscle (preferred site for children); midlateral thigh muscle or upper outer quadrant of buttocks (adults); rotate injection sites.

IV (off-label route): After dilution in admixture, infuse over 30 to 60 minutes (Morris 1994; Peloquin 1992; Tanoira 2014)

Consult your pharmacist.

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

Missed Dose

Consult your pharmacist.

Storage

Consult your pharmacist.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2016. Copyright(c) 2016 First Databank, Inc.

Applies to streptomycin: compounding powder, intramuscular powder for injection

General

Common side effects of streptomycin have included vestibular toxicity (nausea, vomiting, vertigo), paresthesia of the face, rash, fever, urticaria, angioneurotic edema, and eosinophilia. Side effects may be more likely and more severe in patients with underlying renal insufficiency.[Ref]

Nervous system

Nervous system side effects have included eighth cranial nerve toxicity, which typically affects the vestibular system, but may also affect the auditory component. Streptomycin has more vestibulotoxicity than cochlear toxicity. Vestibulotoxicity is usually reversible with early detection and discontinuation of streptomycin. Cochlear toxicity is often irreversible.

A large percentage of patients receiving daily doses of 1.8 to 2 grams are likely to develop symptoms of vestibular toxicity within 4 weeks, especially the elderly or renally impaired.

Scotomas, presenting as blind spots, and peripheral neuritis have been reported.[Ref]

Previous exposure to aminoglycosides, concomitant use of other potentially ototoxic agents (such as aspirin), and advanced age may provide additional risk of ototoxicity. If symptoms of dizziness, ataxia, tinnitus, vertigo, headache, or decreased hearing occur, alternate therapy should be considered. Baseline and monthly auditory testing should be considered during chronic use of streptomycin, such as in the case of tuberculosis therapy, since ototoxicity may be detected before it becomes clinically evident.

Streptomycin has been reported to possess neuromuscular blocking properties. Extremely high doses of streptomycin have allegedly resulted in lethal neuromuscular blockade.[Ref]

Hypersensitivity

Two reported cases of streptomycin hypersensitivity have involved acute renal failure. In one patient hemolytic anemia was also present and antibodies to streptomycin were detected. Each of these patients had received streptomycin prior to the reaction.[Ref]

Hypersensitivity side effects have been reported infrequently. Cases of anaphylaxis, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, pruritus, urticaria, eosinophilia, and rash have been attributed to immune-mediated hypersensitivity reactions to streptomycin. Hypersensitivity myocarditis has also been reported.[Ref]

Renal

Renal side effects have included nephrotoxicity, azotemia, and renal electrolyte wasting. Nephrotoxicity is less common than with other aminoglycosides. Streptomycin-induced nephrotoxicity may be more likely in patients with preexisting renal insufficiency.[Ref]

Risk factors for the development of streptomycin nephrotoxicity include preexisting renal insufficiency, advanced age, concomitant use of other potentially nephrotoxic drugs, and previous exposure to aminoglycoside therapy. Acute renal failure has also occurred as part of an immune-mediated reaction.[Ref]

Hematologic

Aplastic anemia has been reported in patients receiving streptomycin in combination with other antituberculous drugs. Implication of streptomycin as the offending agent is difficult.

The development of a streptomycin-specific antibody directed against red blood cells has been reported, but no hemolysis occurred.[Ref]

Hematologic side effects have included hypersensitivity-associated eosinophilia, and rarely, aplastic anemia, leukopenia, thrombocytopenia, pancytopenia, and hemolytic anemia.[Ref]

Other

Rechallenge with streptomycin reproduced fevers and shaking chills in a patient who had otherwise begun to recover from tuberculosis, was HIV-negative, and who had no other source of infection.[Ref]

Other side effects have included a rare case of recurrent fever and shaking chills. Streptomycin is a potent sensitizer and often causes local irritation in ocular tissues.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea and vomiting, which should be evaluated as possible signs of vestibular ototoxicity.[Ref]

Some side effects of streptomycin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.