Streptomycin is a bactericidal antibiotic that belongs to the aminoglycoside class. Like other drugs in the same class, it has poor absorption when taken orally and is administered either via the intramuscular or the intravenous route.

Streptomycin Uses:

• Tuberculosis:

  • When the principal agents (such as isoniazid, rifampin, ethambutol, or pyrazinamide) are contraindicated or cannot be taken due of toxicity or intolerance, treatment for tuberculosis is combined with other suitable antitubercular medications.

• Non-tuberculosis infections:

  • Treatment of illnesses brought on by vulnerable bacteria that cannot be treated with less hazardous substances, such as:
    • sensitive Yersinia pestis (plague);
    • Francisella tularensis (tularemia);
    • Brucella;
    • Klebsiella granulomatis (donovanosis, granuloma inguinale);
    • Haemophilus influenzae (in respiratory, endocardial, and meningeal infections,
    • Haemophilus ducreyi (chancroid);
    • concomitantly with another antibacterial agent);
    • Escherichia coli,
    • Proteus spp.,
    • Klebsiella pneumoniae pneumonia (concomitantly with another antibacterial agent);
    • Enterobacter aerogenes, K. pneumoniae, and  Streptococcus viridans;
    • E. faecalis (in endocardial infections, concomitant with penicillin);
    • Enterococcus faecalis in urinary tract infections; and
    • gram-negative bacillary bacteremia (concomitant with another antibacterial agent).

• Off Label Use of Streptomycin in Adults:

  • Buruli ulcer (Mycobacterium ulcerans);
  • Ménière’s disease;
  • Mycobacterium avium complex (MAC);
  • Mycobacterium avium complex (MAC) disease, disseminated in HIV persons;
  • Mycobacterium kansasii

Streptomycin Dose in Adults

• Note: drug Manufacturer’s labeling suggest for IM administration only, however, IV administration (off-label route) has also been described.

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

Indication-specific dosing:

Streptomycin Dose in the treatment of Brucellosis:

• IM:dose of 1 g per day divided into 2 to 4 doses for 14 to 21 days (with doxycycline).

Streptomycin Dose in the treatment of Enterococcal Endocarditis:

• Susceptible to penicillin and streptomycin/resistant to gentamicin:

• Native or prosthetic valve:

  • IM, IV: 
• Duration of therapy: 4 weeks (native valve and symptoms present <3 months); ≥6 weeks (native valve and symptoms present ≥3 months or prosthetic valve).

• Manufacturer’s labeling:

  • The prescribing information's suggested dosage could not correspond to current clinical practise.
  • IM: For two weeks, take 1 g every 12 hours; after that, take 500 mg every 12 hours.

Dose in the treatment of Streptococcal infections:

• IM: at 1 g every 12 hours for 1 week, followed by 500 mg every 12 hours for 1 week in combination with penicillin.

Streptomycin Dose in the treatment of Mycobacterium avium complex (MAC) (off-label):

• 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).

Streptomycin Dose in the treatment of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected patients (off label):

• IM, IV:  by 1 g daily as optional adjunct therapy with ethambutol (plus clarithromycin or azithromycin).

Streptomycin Dose in the treatment of Mycobacterium kansasii disease (rifampin-resistant) (off-label):

• IM: 750 mg to 1 g daily (as part of a three-drug regimen based on susceptibilities).

Dose in the treatment of Mycobacterium ulcerans (Buruli ulcers) (off-label):

• 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.

Streptomycin Dose in the treatment of Plague:

• Until the patient has been afebrile for at least two to three days, 30 mg/kg/day (maximum dose: 2 g) split every 12 hours is prescribed.
• Note: Full course is considered for 10 days (CDC 2014; WHO 2009).

• Manufacturer’s labeling:

  • The prescribing information's suggested dosage could not correspond to current clinical practise. 1 g twice per day

Streptomycin Dose in the treatment of Tuberculosis:

• IM, IV: For 2 to 4 months, administer 15 mg/kg (maximum dose: 1 g) once daily for 5 to 7 days a week, then 15 mg/kg (maximum dose: 1 g) twice to three times a week.

• Manufacturer’s labeling:

  • The prescribing information's suggested dosage could not correspond to current clinical practise.
  • 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)

Streptomycin Dose in the treatment of Tularemia: 

• IM 2 g daily in 2 divided doses for ≥10 days.

• Manufacturer’s labeling:

  • The prescribing information's suggested dosage could not correspond to current clinical practise. every 12 hours in divided dosages, 1 to 2 g per day

Streptomycin Dose in Children

• Note: IM route preferred; consider use of IV route in case where IM therapy not tolerated.
• Monitor serum drug concentrations.

Streptomycin General dosing, combination therapy for susceptible infection:

• Manufacturer's labeling:

  • IM: 20 to 40 mg/kg/day divided into 6 to 12 hour intervals;
  • 1,000 mg/dose is maximum dose
  • 2,000 mg/day is maximum daily dose

• Alternate dosing:

  • 20 to 30 mg/kg/day split every 12 hours by IM or IV; the daily limit is 1,000 mg.

Streptomycin Dose in the treatment of enterococcal Endocarditis, resistant to gentamicin:

• IM, IV: 20 to 30 mg/kg/day divided into 12 equal doses; the daily maximum is 2,000 mg;
• used with other antibiotics, adjustment of the dose to target concentrations.

Streptomycin Dose in the treatment of Mycobacterium avium complex:

• Adolescents:

  • IM, IV: a dose of 1,000 mg once daily as part of combination therapy.

Streptomycin dose in the treatment of Mycobacterium ulcerans (Buruli ulcers):

• IM: at 15 mg/kg one time a day daily;
• 1,000 mg/day is maximum daily dose
• used in combination with rifampin for 2 months, or may use this combination for 4 weeks, followed by 4 weeks of rifampin and clarithromycin combination therapy.

Streptomycin Dose in the treatment of Plague:

• IM, IV: 30 mg/kg/day split into 12 hour intervals for 10 days;
• 2,000 mg/day is maximum daily dose

Streptomycin Dose in the treatment of active Tuberculosis as a second-line therapy, multidrug-resistant (MDR) Tuberculosis or TB-meningitis:

• Note:
  • Always take it in conjunction with other medications.
  • Less frequent dose schedules for medications should be administered as directly observed therapy (DOT).
  • Depending on the patient's sensitivity and clinical response, multiple MDR TB treatment plans are available.
  • Streptomycin frequency and dosing vary based on the chosen treatment plan; for thorough and complete information, reference the most recent drug-sensitive TB guidelines.

Primary pulmonary disease:

• Once-daily therapy:

  • Infants, Children, and Adolescents <15 years weighing ≤40 kg:

    • Note: Suggested expert dosing range is large and variable.
    • IM, IV: 15 to 40 mg/kg/dose one time daily;
    • Initially, some experts advise a dose of 15 to 20 mg/kg administered once daily;
    • 1,000 mg/day is maximum daily dose
    • monitor serum concentrations.
    • Note: Some clinicians suggest every 12-hour dosing may be utilized.

  • Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years:

    • IM, IV: The maximum daily dose is 1,000 mg, and the serum concentrations should be monitored at 15 mg/kg once daily.  (ATS/CDC/IDSA [Nahid 2016]; Pérez Tanoira 2014)

• Three-times-weekly DOT:

  • Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years:

    • IM, IV: Three times per week at a dose of 25 mg/kg; the maximum dose is 1 mg/dose.

• Twice weekly DOT:

  • Infants, Children, and Adolescents <15 years weighing ≤40 kg:

    • IM, IV: 25 to 30 mg/kg/dose twice weekly; maximum dose: 1,000 mg/dose (ATS/CDC/IDSA [Nahid 2016])

Dose in the treatment of Meningitis (independent of HIV-status):

Note: Suggested expert dosing range is large and variable (Schaaf 2015):

• IM, IV:15 to 40 mg/kg/dose given once daily; some experts advise starting with 15 to 20 mg/kg/dose given once daily;
• maximum daily dose: 1,000 mg/day;
• monitor serum concentrations.

Dose in the treatment of Tularemia:

• IM: for 10 days 15 mg/kg/dose two times daily ;
• 2,000 mg/day is maximum daily dose

Pregnancy Risk Factor D

• The placenta can absorb streptomycin.
• If Streptomycin is administered during pregnancy, it can cause harm to the fetus.
• Multiple reports have been made of children who received streptomycin from their mothers during pregnancy.
• Streptomycin should not be used as a substitute for it in the treatment of tuberculosis during pregnancy.

Streptomycin use during breastfeeding:

• Breast milk contains streptomycin.
• The potential for severe side effects in nursing infants is why the drug manufacturer suggests that you decide whether to stop nursing or discontinue using the drug.
• The significance of the mother's care should be considered when making this choice.
• A nursing infant's exposure to aminoglycosides as a class is likely to be limited by how poorly they are dispersed in breast milk.
• Any antibiotic may cause a modification in the bowel flora.

Streptomycin Dose in Kidney Disease:

• The medicine manufacturer's labelling does not mention dosage changes, although the following ones have been suggested:

• Aronoff 2007:

Note: Recommendations are based on doses of 1 to 2 g every 6 to 12 hours (1 g once daily for tuberculosis):

• CrCl >50 mL/minute:

  • Dosage adjustment not necessary.

• CrCl 10 to 50 mL/minute:

  • Administer every 24 to 72 hours.

• CrCl <10 mL/minute:

  • Administer every 72 to 96 hours.

• End-stage renal disease (ESRD):

  • Intermittent hemodialysis (IHD):

    • One-half of the recommended dose administered after hemodialysis on dialysis days.
  • Note: Dosing is based on the premise that IHD sessions are completed three times a week.

  • Peritoneal dialysis (PD):

    • Administration via PD fluid: 20 to 40 mg/L (20 to 40 mcg/mL) of PD fluid

  • Continuous renal replacement therapy (CRRT):

  • Administer every 24 to72 hours; monitor levels.
  • Note:
    • The technique of renal replacement, the type of filter, and the flow rate all have a significant impact on drug clearance.
    • Close monitoring of the pharmacologic response, warning indicators of drug accumulation, and drug concentrations in respect to the target trough are all necessary for proper dosing (if appropriate).

• ATS 2003 Guidelines:

  • Tuberculosis:

    • CrCl ≥30 mL/minute:

      • Dosage adjustment not necessary.

    • CrCl <30 mL/minute:

      • doses of 12 to 15 mg/kg (maximum dose: 1 g) 2-3 times each week

    • End-stage renal disease (ESRD) on intermittent hemodialysis (IHD):

      • doses of 12 to 15 mg/kg (maximum dose: 1 g) 2-3 times each week

Streptomycin Dose in Liver disease:

• The labelling on the medication from the manufacturer does not mention dosage adjustments.

Streptomycin Side effects:

• Cardiovascular:

  • Hypotension

• Central Nervous System:

  • Drug Fever
  • Facial Paresthesia
  • Headache
  • Neurotoxicity

• Dermatologic:

  • Exfoliative Dermatitis
  • Skin Rash
  • Urticaria

• Gastrointestinal:

  • Nausea
  • Vomiting

• Genitourinary:

  • Azotemia
  • Nephrotoxicity

• Hematologic & Oncologic:

  • Eosinophilia
  • Hemolytic Anemia
  • Leukopenia
  • Pancytopenia
  • Thrombocytopenia

• Hypersensitivity:

  • Anaphylaxis
  • Angioedema

• Neuromuscular & Skeletal:

  • Arthralgia
  • Tremor
  • Weakness

• Ophthalmic:

  • Amblyopia

• Otic:

  • Auditory Ototoxicity
  • Vestibular Ototoxicity

• Respiratory:

  • Dyspnea

Contraindications to Streptomycin:

• hypersensitivity or hyperresponsiveness to any ingredient in the formulation, including streptomycin, other aminoglycosides, or both

Warnings and precautions

• The US Boxed Warning: Neuromuscular Blockade and Respiratory Paralysis

  • If taken right after anaesthesia or muscle relaxants, this may result in neuromuscular blockade and paralysis of the breathing muscles.

• Neurotoxicity: [US Boxed Warn]

  • Neurotoxicity may occur, which is a condition that causes disturbances in vestibular or cochlear function, peripheral neuritis and encephalopathy.Common risk factors include concomitant neurotoxic and/or neuro-/nephrotoxic medication, pre-existing renal impairment.
  • The amount of drug taken and the length of treatment are both factors that contribute to ototoxicity.
  • Vertigo and tinnitus could indicate vestibular injury or impending bilateral irreversible damages.
  • Long-term therapy is recommended for those who are able to tolerate periodic and baseline caloric stimulation as well as audiometric testing.
  • If you notice signs of ototoxicity, discontinue treatment.

• Superinfection

  • Long-term use may result in fungal or bacterial superinfection, including pseudomembranous colitis and C. difficile-associated diarrhoea (CDAD); CDAD has been noted more than two months after receiving antibiotic treatment.

• Hearing impairment:

  • Patients with hearing loss, vertigo, or tinnitus should be cautious.

• Neuromuscular disorders:

  • Patients with neuromuscular conditions like myasthenia gravis need to be handled carefully.

• Renal impairment: [US-Boxed Warning]

  • Could cause nephrotoxicity.
  • Patients with impaired renal function should be cautious.
  • It may be necessary to alter the dose for patients who have nitrogen retention or renal impairment.
  • Keep an eye on your renal function.
  • Peak serum concentrations shouldn't be more than 20–25 mcg/mL in patients with severe renal impairment.

Streptomycin: Drug Interaction

Monitoring parameters:

• Baseline and periodic hearing tests 
• BUN
• Creatinine
• Serum drug concentrations ,

How to administer Streptomycin?

• IM: Inject deeply IM into large muscle mass; mid-lateral thigh muscle or upper outer quadrant of the buttocks; rotate injection sites.
• IV (off-label route): After dilution in admixture, infuse over time period of 30 to 60 minutes.

Mechanism of action of Streptomycin:

• By binding to the 30S subunits of the ribosomal 30S ribosomal ribosomal sulfate, inhibits bacterial protein synthesis.
• This in turn causes a faulty peptide sequence in the protein chain.

Absorption:

• Oral: Poorly absorbed;
• IM: Well absorbed

Distribution:

• Except for the brain, distributes to most bodily tissues and fluids; a tiny amount only enters the CSF in cases of inflamed meninges.

Protein binding: 34% Half-life elimination:

• Newborns: 4 to 10 hours; Adults: ~2 to 4.7 hours; prolonged with renal impairment

Time to peak:

• IM: Within 1 to 2 hours

Excretion:

• Urine (29% to 89% excreted as unchanged drug); a small amount (1%) excreted in bile, saliva, sweat, and tears

International Brands of Streptomycin:

• Streptomycin
• Ambistryn-S
• Estrepto-Monaxin
• Estreptomicina
• Strepiovit
• Strepto
• StreptoHefa
• Streptocin
• Streptomycinum
• Streptosol
• Streptoz
• Stretopen

Streptomycin Brand Names in Pakistan: