THE RISK OF SEVERE NEUROTOXIC REACTIONS IS SHARPLY INCREASED IN PATIENTS WITH IMPAIRED RENAL FUNCTION OR PRE-RENAL AZOTEMIA. THESE INCLUDE DISTURBANCES OF VESTIBULAR AND COCHLEAR FUNCTION, OPTIC NERVE DYSFUNCTION, PERIPHERAL NEURITIS, ARACHNOIDITIS, AND ENCEPHALOPATHY MAY ALSO OCCUR. THE INCIDENCE OF CLINICALLY DETECTABLE, IRREVERSIBLE VESTIBULAR DAMAGE IS PARTICULARLY HIGH IN PATIENTS TREATED WITH STREPTOMYCIN.
RENAL FUNCTION SHOULD BE MONITORED CAREFULLY; PATIENTS WITH RENAL IMPAIRMENT AND/OR NITROGEN RETENTION SHOULD RECEIVE REDUCED DOSES. THE PEAK SERUM CONCENTRATION IN INDIVIDUALS WITH KIDNEY DAMAGE SHOULD NOT EXCEED 20 TO 25 MCG/ML.
THE CONCURRENT OR SEQUENTIAL USE OF OTHER NEUROTOXIC AND/OR NEPHROTOXIC DRUGS WITH STREPTOMYCIN SULFATE, INCLUDING NEOMYCIN, KANAMYCIN, GENTAMICIN, CEPHALORIDINE, PAROMOMYCIN, VIOMYCIN, POLYMYXIN B, COLISTIN, TOBRAMYCIN AND CYCLOSPORINE SHOULD BE AVOIDED.
THE NEUROTOXICITY OF STREPTOMYCIN CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKAGE, ESPECIALLY WHEN THE DRUG IS GIVEN SOON AFTER THE USE OF ANESTHESIA OR MUSCLE RELAXANTS.
THE ADMINISTRATION OF STREPTOMYCIN IN PARENTERAL FORM SHOULD BE RESERVED FOR PATIENTS WHERE ADEQUATE LABORATORY AND AUDIOMETRIC TESTING FACILITIES ARE AVAILABLE DURING THERAPY.
Streptomycin is a water-soluble aminoglycoside derived from Streptomyces griseus. It is marketed as the sulfate salt of streptomycin.
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:
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.
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.
Pasteurella pestis (plague),
Francisella tularensis (tularemia),
Calymmatobacterium granulomatis (donovanosis, granuloma inguinale),
H. ducreyi (chancroid),
H. influenzae (in respiratory, endocardial, and meningeal infections-concomitantly with another antibacterial agent),
K. pneumoniae pneumonia (concomitantly with another antibacterial agent),
E.coli, Proteus, A. aerogenes, K. pneumoniae, and Enterococcus faecalis in urinary tract infections,
Streptococcus viridans, Enterococcus faecalis (in endocardial infections -concomitantly with penicillin),
Gram-negative bacillary bacteremia (concomitantly with another antibacterial agent).
To reduce the development of drug-resistant bacteria and maintain the effectiveness of streptomycin and other antibacterial drugs, streptomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Published Studies Related to Streptomycin
Comparison of the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks versus streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis: a randomized clinical trial. [2010.05]
OBJECTIVES: To compare the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks with streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis... CONCLUSIONS: The results show that the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks is not superior to that of streptomycin for 2 weeks plus doxycycline for 45 days.
Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans. [2006.04.15]
BACKGROUND: In the treatment of human brucellosis, antibiotic regimens containing an aminoglycoside are reportedly associated with fewer relapses... CONCLUSIONS: The combination of oral doxycycline for 45 days plus intramuscular gentamicin for 7 days is equally as effective as traditional therapy using doxycycline for 45 days plus streptomycin for 14 days.
Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans. [2005.08]
Mycobacterium ulcerans disease is common in some humid tropical areas, particularly in parts of West Africa, and current management is by surgical excision of skin lesions ranging from early nodules to extensive ulcers (Buruli ulcer). Antibiotic therapy would be more accessible to patients in areas of Buruli ulcer endemicity...
Comparison of the efficacy of a subunit and a live streptomycin-dependent porcine pleuropneumonia vaccine. [2004.06]
OBJECTIVE: To evaluate the efficacy of two new-generation porcine pleuropneumonia vaccines when challenged with Australian isolates of Actinobacillus pleuropneumoniae of serovars 1 and 15... CONCLUSIONS: Both of the vaccines provided significant protection against a severe challenge with serovar 1 A pleuropneumoniae. Neither vaccine was effective against a serovar 15 A pleuropneumoniae challenge. There was evidence that the Porcilis APP vaccine did provide some protection against the serovar 15 challenge because the ADG, after challenge of pigs given this vaccine, was greater than the control pigs.
The early bactericidal activity of streptomycin. [2002.08]
SETTING: Patients with sputum smear-positive, newly diagnosed pulmonary tuberculosis studied at Tygerburg Hospital, Cape Town, for their early response to streptomycin (SM). OBJECTIVE: To determine the standard early bactericidal activity (EBA), namely the fall in viable counts of tubercle bacilli in 16-hour sputum collections during the first 2 days of treatment with SM... CONCLUSIONS: The low EBAs show that SM has low, dose-related, bactericidal activity in cavities, consistent with results from clinical trials. If streptomycin-resistant bacilli are present, paromomycin is probably the aminoglycoside of choice.
Clinical Trials Related to Streptomycin
WHO Drug Study for Buruli Ulcer - Comparison of SR8 and CR8 [Recruiting]
This is a WHO-sponsored trial.
Combination therapy with streptomycin and rifampicin has been the standard antibiotic
treatment for M. ulcerans infection since 2004. In March 2010, a WHO Technical Advisory
Group recommended that a trial be carried out to develop a fully oral treatment for the
disease. Although the current treatment is effective, injection with streptomycin is a
problem. Several small observational studies (published and unpublished) have shown that a
fully oral treatment is promising.
This WHO sponsored study will be a randomized, controlled open label non-inferiority phase
II/III, multi-centre trial (1 centre in Benin and 4 centres in Ghana), with two parallel
treatment groups. The ultimate goal is to search for an effective alternative treatment to
the current standard WHO-recommended therapy for all forms of Buruli ulcer, which includes
injections of streptomycin with inherent logistic, operational and safety disadvantages.
Financial and material support:
1. American Leprosy Missions, USA
2. Raoul Follereau Foundation, France
3. MAP International, USA
4. Sanofi, France
5. 7th Framework Programme of the European Union: BuruliVac project (241500)
6. Aranz Medical Limited, New Zealand
Pilot Randomized Study of Paromomycin (Aminosidine) vs Streptomycin for Uncomplicated Pulmonary Tuberculosis [Completed]
OBJECTIVES: I. Compare the pharmacokinetics and early bactericidal activity of paromomycin
(aminosidine) vs streptomycin for the treatment of uncomplicated pulmonary tuberculosis.
II. Compare the tolerability of these two drugs in these patients. III. Establish the
relationships between achieved serum concentration, minimal inhibitory concentration, and
early bactericidal activity of paromomycin and streptomycin.
BURULICO Drug Trial Study Protocol: RCT SR8/SR4+CR4, GHANA [Completed]
The standard for treatment Buruli ulcer disease (BUD) used to be surgery but the WHO now
advises streptomycin (S, 15 mg/kg daily, intramuscularly) and rifampicin (R,10 mg/kg daily)
along with surgery. This preliminary advice was based on observations in 21 patients with
pre-ulcerative lesions of BUD, who were given daily SR treatment for varying periods of
time. In patients treated with SR for at least 4 weeks, M. ulcerans could no longer be
cultured from excised lesions. SR has been introduced without a formal evaluation or
comparison with other treatments have been conducted or published, but the impression is
that this treatment is beneficial and may cure BUD without additional surgical management.
This study protocol evaluated the hypothesis that early, limited lesions of
BUD(pre-ulcerative or ulcerated lesions, ≤ 10 cm maximum diameter), can be healed without
recurrence using antimycobacterial drug therapy, without the need for debridement surgery.
In endemic regions in Ghana, patients will be actively recruited and followed if ≥ 5 years
of age, and with early (i. e., onset < 6 months) BUD.
- consent by patients and / or care givers / legal representatives
- clinical evaluation, and by
- analysis of three 0. 3 cm punch biopsies under local anaesthesia.
- disease confirmation: dry reagent-based polymerase chain reaction (DRB-PCR IS2404)
- randomization: either SR for 8 weeks, or 4 weeks of SR followed by R and clarithromycin
- stratification: ulcerative or pre-ulcerative lesions.
Biopsies processed for histopathology, DRB-PCR-, microscopy, culture, genomic, and
sensitivity tests. Lesions assessed regularly for progression or healing during treatment.
Drug toxicity monitoring included blood cell counts, liver enzymes and renal tests; and ECG
and audiographic tests.
Primary endpoint: healing without recurrence at 12 months follow-up after start of treatment
Secondary endpoint: reduction in lesion surface area and/or clinically assessed improvement
on completion of treatment, averting the need for debridement surgery.
Recurrences biopsied for confirmation, using PCR, histopathology, and culture. Sample size
calculation: 2x74 fully evaluable patients; 80% power to detect a difference of 20 % in
recurrence-free cure 12 months after start of treatment between the two groups (60 versus
80%). A Data Safety and Monitoring Board made interim analysis assessments.
Treatment and Diagnosis of Plague [Completed]
This clinical trial will compare the effectiveness of streptomycin, which historically is
the standard drug for treatment of plague, with gentamicin. The hypothesis is that
gentamicin is not inferior to streptomycin but that it will have less severe side effects.
The study is being done in Madagascar because that country reports the most plague cases in
the world. Patients coming into a participating clinic with suspected plague (bubonic,
pneumonic, or septicemic) will be randomized into one of two treatment arms after giving
informed consent. Patients will be monitored for side effects and for improvement of
In addition, rapid diagnostic test strips have been developed but not fully evaluated for
use on humans. The investigators will evaluate these new tests on specimens from the same
patients, comparing their performance with that of classical diagnostic methods such as
culture and serology.
Timing of Surgical Intervention in Buruli Ulcer Patients Treated With Antibiotics [Active, not recruiting]
Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic
in West Africa. It often leads to functional limitations. Treatment was by extensive
surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and
streptomycin was added. Observation of Buruli ulcer lesions of limited size during
antibiotic treatment showed that during treatment there is a paradoxical increase of the
lesion, with a decrease of the lesion after week 14. Current WHO protocols advise to decide
whether surgery is needed four weeks after the start of antibiotics. This might be too early
in the healing process. The investigators hypothesize that delay in surgery is safe, and
that it results in a reduction of the number of surgical interventions.
Primary Objective of this study is to compare the need for surgical treatment in standard
timing of surgery at the end of eight weeks antimicrobial treatment with a policy to
postpone surgical treatment until week 14.
Secondary Objectives are to study whether postponing surgery leads to less extensive surgery
and a change in frequency of functional limitations;
Patients will be randomized for surgery at week 8 after start of antibiotic treatment and
week 14 after start of treatment. Reasons for treating doctors to decide to intervene with
surgery will be according to current clinical practice and will be clearly defined in this
protocol. Standard care of eight weeks of rifampicin and streptomycin will be given. All
patients will be followed and lesional size using acetate sheet recordings will be used
Study population: Patients with a clinical picture of Buruli ulcer disease confirmed by
diagnostic tests in the districts covered by the Buruli ulcer centers in Lalo and Allada,
Benin. Patients who are pregnant, have a contraindication for general anaesthesia and
children below three years old will be excluded. 130 Patients in each treatment arm will be
included to detect a difference in percentage of patients needing surgery of 20 percent.
Main study parameters/endpoints: Primary outcome measure is the number of patients healed
without surgery. Secondary outcome measures are the extent of surgery by measurement of
lesional size, functional limitations after the end of treatment and one year after the
start of treatment and the duration of admission.
Reports of Suspected Streptomycin Side Effects
Drug Ineffective (5),
Vitamin D Deficiency (3),
Hepatic Function Abnormal (3),
Mycobacterium Avium Complex Infection (3),
Interstitial Lung Disease (3), more >>
Page last updated: 2010-10-05