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 

General

Prescribing streptomycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Baseline and periodic caloric stimulation tests and audiometric tests are advisable with extended streptomycin therapy. Tinnitus, roaring noises, or a sense of fullness in the ears indicates need for audiometric examination or termination of streptomycin therapy or both.

Care should be taken by individuals handling streptomycin for injection to avoid skin sensitivity reactions. As with all intramuscular preparations, Streptomycin Sulfate Injection should be injected well within the body of a relatively large muscle and care should be taken to minimize the possibility of damage to peripheral nerves. (See DOSAGE AND ADMINISTRATION.)

Extreme caution must be exercised in selecting a dosage regimen in the presence of pre-existing renal insufficiency. In severely uremic patients a single dose may produce high blood levels for several days and the cumulative effect may produce ototoxic sequelae. When streptomycin must be given for prolonged periods of time alkalinization of the urine may minimize or prevent renal irritation.

A syndrome of apparent central nervous system depression, characterized by stupor and flaccidity, occasionally coma and deep respiratory depression, has been reported in very young infants in whom streptomycin dosage had exceeded the recommended limits. Thus, infants should not receive streptomycin in excess of the recommended dosage.

In the treatment of venereal infections such as granuloma inguinale, and chancroid, if concomitant syphilis is suspected, suitable laboratory procedures such as a dark field examination should be performed before the start of treatment, and monthly serologic tests should be done for at least four months.

As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be instituted.

Information for Patients

Patients should be counseled that antibacterial drugs including streptomycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When streptomycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by streptomycin or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose ofthe antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

The ototoxic effects of the aminoglycosides, including streptomycin, are potentiated by the co-administration of ethacrynic acid, furosemide, mannitol and possibly other diuretics.

Pregnancy

Category D: See WARNINGS section.

Nursing Mothers

Because of the potential for serious adverse reactions in nursing infants from streptomycin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

(See DOSAGE AND ADMINISTRATION.)

Intramuscular Route Only

Adults: The preferred site is the upper outer quadrant of the buttock, (i.e., gluteus maximus), or the mid-lateral thigh.

Children: It is recommended that intramuscular injections be given preferably in the mid-lateral muscles of the thigh. In infants and small children the periphery of the upper outer quadrant of the gluteal region should be used only when necessary, such as in burn patients, in order to minimize the possibility of damage to the sciatic nerve.

The deltoid area should be used only if well developed such as in certain adults and older children, and then only with caution to avoid radial nerve injury. Intramuscular injections should not be made into the lower and mid-third of the upper arm. As with all intramuscular injections, aspiration is necessary to help avoid inadvertent injection into a blood vessel.

Injection sites should be alternated. As higher doses or more prolonged therapy with streptomycin may be indicated for more severe or fulminating infections (endocarditis, meningitis, etc.), the physician should always take adequate measures to be immediately aware of any toxic signs or symptoms occurring in the patient as a result of streptomycin therapy.

1.  TUBERCULOSIS: The standard regimen for the treatment of drug susceptible tuberculosis has been two months of INH, rifampin and pyrazinamide followed by four months of INH and rifampin (patients with concomitant infection with tuberculosis and HIV may require treatment for a longer period). When streptomycin is added to this regimen because of suspected or proven drug resistance (see INDICATIONS AND USAGE section), the recommended dosing for streptomycin is as follows:

Streptomycin is usually administered daily as a single intramuscular injection. A total dose of not more than 120 g over the course of therapy should be given unless there are no other therapeutic options. In patients older than 60 years of age the drug should be used at a reduced dosage due to the risk of increased toxicity. (See BOXED WARNING.)

Therapy with streptomycin may be terminated when toxic symptoms have appeared, when impending toxicity is feared, when organisms become resistant, or when full treatment effect has been obtained. The total period of drug treatment of tuberculosis is a minimum of 1 year; however, indications for terminating therapy with streptomycin may occur at any time as noted above.

2.  TULAREMIA: One to 2 g daily in divided doses for 7 to 14 days until the patient is afebrile for 5 to 7 days.

3.  PLAGUE: Two grams of streptomycin daily in two divided doses should be administered intramuscularly. A minimum of 10 days of therapy is recommended.

4.  BACTERIAL ENDOCARDITIS:

a. Streptococcal endocarditis; in penicillin-sensitive alpha and non-hemolytic streptococcal endocarditis (penicillin MIC<0.1 mcg/mL), streptomycin may be used for 2-week treatment concomitantly with penicillin. The streptomycin regimen is 1 g b.i.d. for the first week, and 500 mg b.i.d. for the second week. If the patient is over  60 years of age, the dosage should be 500 mg b.i.d. for the entire 2- week period.

b. Enterococcal endocarditis: Streptomycin in doses of 1 g b.i.d. for 2 weeks and 500 mg b.i.d. for an additional 4 weeks is given in combination with penicillin. Ototoxicity may require termination of the streptomycin prior to completion of the 6-week course of treatment.

5.  CONCOMITANT USE WITH OTHER AGENTS: For concomitant use with other agents to which the infecting organism is also sensitive: Streptomycin is considered a secondline agent for the treatment of gram-negative bacillary bactermia, meningitis, and pneumonia; brucellosis; granuloma inguinale; chancroid, and urinary tract infection.

For adults: 1 to 2 grams in divided doses every six to twelve hours for moderate to severe infections. Doses should generally not exceed 2 grams per day.

For children: 20 to 40 mg/kg/day (8 to 20 mg/lb/day) in divided doses every 6 to 12 hours. (Particular care should be taken to avoid excessive dosage in children).

The dry lyophillized cake is dissolved by adding Water for Injection USP in an amount to yield the desired concentration as indicated in the following table:

Sterile reconstituted solutions should be protected from light and may be stored at room temperature for one week without significant loss of potency

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit

STORAGE

Store dry powder under controlled room temperature 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

PROTECT FROM LIGHT