Streptomycin Sulfate (streptomycin sulfate)

Dosage of streptomycin sulfate is expressed in terms of streptomycin.

Like other aminoglycosides, dosage of streptomycin should individualized taking into consideration the patient's pretreatment body weight, renal status, severity of the infection, and susceptibility of the causative organism.

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, peak and trough serum concentrations of streptomycin should be monitored and dosage adjusted to maintain desired serum concentrations. (See Dosage and Administration: Dosage, in the Aminoglycosides General Statement 8:12.02.) A causal relationship between maintenance of certain peak or trough serum concentrations or other pharmacodynamic endpoints and clinical response or toxicity has not been established to date for streptomycin dosing regimens. However, suggested desirable peak and trough serum concentrations of streptomycin are 5-35 mcg/mL and less than 5-10 mcg/mL, respectively. Peak serum streptomycin concentrations greater than 40-50 mcg/mL may be associated with toxicity; some clinicians state that persistent concentrations greater than 20 mcg/mL should be avoided. For the treatment of enterococcal endocarditis, the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend that streptomycin dosage be adjusted to achieve 1-hour peak serum concentrations of 20-35 mcg/mL and trough concentrations less than 10 mcg/mL.

Although streptomycin dosage regimens that involve once-daily (single-daily) dosing are recommended for the treatment of tuberculosis and brucellosis, once-daily streptomycin regimens are not usually recommended for other indications and should not be used for the treatment of enterococcal or streptococcal endocarditis.

In patients with impaired renal function, doses and/or frequency of administration of streptomycin must be modified in response to serum concentrations of the drug and the degree of renal impairment. Because of the increased risk of ototoxicity and nephrotoxicity, streptomycin should be used with caution in patients with impaired renal function and serum concentrations of the drug monitored closely. The manufacturer recommends that peak serum concentrations of streptomycin should not exceed 20-25 mcg/mL in patients with renal impairment.

Some clinicians recommend that adults with renal impairment receive an initial streptomycin loading dose of 15 mg/kg (approximately 1 g) of streptomycin. For subsequent therapy, these clinicians recommend that patients with creatinine clearances of 50-80 mL/minute receive 7.5 mg/kg once every 24 hours, those with creatinine clearances of 10-50 mL/minute receive 7.5 mg/kg once every 24-72 hours, and those with creatinine clearances less than 10 mL/minute receive 7.5 mg/kg once every 72-96 hours. 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.

For the treatment of active tuberculosis in adults with renal impairment, the ATS, CDC, and IDSA recommend that usual doses be given at less frequent intervals since use of lower doses may reduce efficacy of the drug. These experts recommend that adults with renal impairment receive streptomycin in a dosage of 12-15 mg/kg daily given 2 or 3 times weekly. If the patient is receiving hemodialysis, the dose should be given after the procedure is finished. In addition, serum concentrations of the drug be should monitored to avoid toxicity.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

Selected Nephrotoxic Agents/Bacitracin

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Bacitracin may cause renal failure due to glomerular and tubular necrosis. Concurrent administration of other nephrotoxic agents may result in additive renal toxicity.(1-3)

CLINICAL EFFECTS: Concurrent use of bacitracin with other potentially nephrotoxic agents may result in renal toxicity.(1-3)

PREDISPOSING FACTORS: Dehydration and high-dose bacitracin may predispose to adverse renal effects.(1)

PATIENT MANAGEMENT: Health Canada states that bacitracin is contraindicated in patients with renal impairment, including those taking other nephrotoxic drugs.(1) The Canadian and US manufacturers of bacitracin state that concomitant use of bacitracin with other potentially nephrotoxic agents should be avoided.(2,3)

DISCUSSION: Renal impairment is a major toxicity of bacitracin. Cases of nephrotoxicity have been reported when bacitracin was used off-label.(1-3)

Selected Nephrotoxic Agents/Polymyxin B

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Polymyxin B can cause nephrotoxicity with a slight degree of tubular damage. Concurrent administration of other nephrotoxic agents may result in an increased risk of nephrotoxicity.(1)

CLINICAL EFFECTS: Concurrent use of polymyxin B with other nephrotoxic agents may result in additive nephrotoxic effects. Polymyxin B nephrotoxicity is characterized by albuminuria, cellular casts, azotemia, diminished urine output, elevated BUN and rising blood levels usually after about 4 days of therapy.(1,2)

PREDISPOSING FACTORS: Factors predisposing to nephrotoxicity include higher cumulative doses and longer duration of therapy of polymyxin B and exposure to multiple nephrotoxins.(2)

PATIENT MANAGEMENT: Concurrent or sequential use of potentially nephrotoxic agents with polymyxin B should be avoided. If concurrent use is necessary, it should be undertaken with great caution. Check renal function at baseline and monitor renal function and polymyxin B blood levels frequently during therapy.(1)

DISCUSSION: Polymyxin B is associated with high rates of nephrotoxicity. Concurrent use with other nephrotoxins may increase the risk of nephrotoxicity.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Aminoglycosides/Anesthetics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neuromuscular blocking activity of aminoglycosides results from a decreased sensitivity at the postjunctional membrane and interfere with transmitter release.(1) These actions produce a synergistic effect with anesthetic agents that produce neuromuscular blockade.(2,3) Some anesthetics cause renal failure due to release of fluoride ion. Aminoglycosides cause nephrotoxicity when high doses are given.(4,5)

CLINICAL EFFECTS: Increased neuromuscular blockade activity, profound sedation, respiratory depression, coma, and/or death. Circulatory collapse may also occur secondary to the neuromuscular blockade.(6-10) Decreased urinary output and increased BUN and serum creatinine may indicate renal impairment.

PREDISPOSING FACTORS: Patients in respiratory distress, history of renal impairment and high doses of aminoglycosides and anesthetics.

PATIENT MANAGEMENT: Monitor neuromuscular blockade with train-of-four stimulus. Monitor vital signs, and respiratory rate. Intravenous neostigmine (0.2 to 2.5 mg), calcium (1 G), and possibly sodium bicarbonate (dose not reported) may be beneficial in reversal of neuromuscular blockade and respiratory depression.(6-10) Supportive care and ventilation should be utilized until the neuromuscular blockade is resolved. Volume replacement may be necessary for circulatory collapse.(6-10) Monitor BUN, serum creatinine, and urinary output and adjust aminoglycoside and anesthetic doses according to renal function.

DISCUSSION: Aminoglycosides including kanamycin(6,11), streptomycin(6,13), amikacin(13), gentamicin(7,13-15), neomycin, and tobramycin(13) have been documented to have neuromuscular blocking activity. There is no documentation with netilmicin and paromomycin, though it is assumed that they produce the same effects as the other members of this class. Neomycin has been shown to interact with cyclopropane(8,9), halothane(6), methoxyflurane(6), and nitrous oxide(6). Enflurane, ethylene, and isoflurane share similar properties to the previous inhalation anesthetics and would likely interact with neomycin. Kanamycin(6,11) and streptomycin (6,12) are known to interact with ether. Gentamicin has been reported to potentiate atracurium.(16) Therefore it is hypothesized that all aminoglycosides interact with the inhaled anesthetics. One study evaluating gentamicin and halothane in animals did not exhibit a decrease in muscle strength.(17) Aminoglycosides have been proven to be nephrotoxic at high doses. Anesthetics containing fluoride also produce renal dysfunction. Nephrotoxicity occurred more often when gentamicin or tobramycin were given with enflurane than when enflurane was given alone or in patients who received nitrous oxide and opioid anesthesia.(4)

Aminoglycosides/Cyclosporine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Cyclosporine and aminoglycosides can both cause nephrotoxicity. Concurrent administration may result in an additive or synergistic risk of nephrotoxicity.(1-3)

CLINICAL EFFECTS: Concurrent use of cyclosporine with aminoglycosides may result in a higher risk of renal dysfunction, including structural kidney damage.(1-3)

PREDISPOSING FACTORS: Factors predisposing to nephrotoxicity include pre-existing renal impairment, older age, higher doses or longer treatment duration of either drug, and dehydration.(1-3)

PATIENT MANAGEMENT: Avoid the concurrent use of cyclosporine and aminoglycosides whenever possible.(2,3) If concurrent use cannot be avoided, it should be undertaken with great caution. Minimize the cyclosporine dose and monitor renal function carefully. Frequent dose adjustment may be indicated. If renal function deteriorates, the aminoglycoside may need to be decreased or discontinued.(1-4)

DISCUSSION: Coadministration of cyclosporine with other drugs that may impair renal function, like aminoglycosides, may cause additive or synergistic impairment of renal function. A meta-analysis of 30 studies that evaluated the correlation and risk factors between cyclosporine and kidney injury in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients included 7 studies that examined the role of the combination with other drugs in the development of nephrotoxicity. Coadministration of aminoglycosides and amphotericin B were independent risk factors for acute or chronic kidney diseases related to cyclosporine in allo-HSCT patients.(5)

Misc Antibiotics/Neuromuscular Blocking Agents

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aminoglycosides, bacitracin, clindamycin, lincomycin, and polymyxins may enhance the pharmacologic effects of neuromuscular blocking agents.

CLINICAL EFFECTS: May see an increase in the pharmacologic effects of neuromuscular blocking agents, including prolonged respiratory depression and apnea.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly.

DISCUSSION: Concomitant administration of aminoglycosides, bacitracin, clindamycin, lincomycin, and polymixins with neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and fatal apnea. The interaction usually occurs when the antibiotic is given prior to or concurrently with the neuromuscular blocking drug, but it may also occur when given after administration. Any antibiotic dosage or route of administration may produce respiratory depression.

Selected Antimycobacterials/Live Bcg

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Bacillus Calmette-Guerin (BCG) is a live, attenuated strain of Mycobacterium bovis (M.bovis) used to induce a granulomatous response in the treatment of localized bladder cancer and as a vaccine to prevent tuberculosis.(1-2) Co-treatment with antibacterial agents active against M.bovis may lead to an attenuation of the immune response associated with BCG administration.(1-2)

CLINICAL EFFECTS: The effectiveness of chemotherapy may be impaired, or the vaccine may be ineffective. Agents linked to this monograph may have activity against M.bovis: amikacin, capreomycin, ciprofloxacin, clofazimine, cycloserine, ethambutol, ethionamide, gatifloxacin, isoniazid, kanamycin, levofloxacin, moxifloxacin, ofloxacin, rifabutin, rifampin, rifapentine, and streptomycin.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Intravesical instillation of BCG should be postponed during treatment with antibacterials which may decrease effectiveness.(2) Administration of BCG vaccine to patients receiving antibiotic therapy should only be done under close medical supervision.(1) If a patient develops a systemic BCG infection due to intravesicular or vaccine administration, treatment with multiple antimycobacterial agents may be required.

DISCUSSION: Because antibiotic therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of BCG vaccine states that administration of BCG vaccine to patients receiving antibiotic therapy should only be done under close medical supervision.(1) Pyrazinamide is not included in this interaction as BCG is not sensitive to pyrazinamide.(2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Aminoglycosides/Loop Diuretics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The coadministration of aminoglycosides and loop diuretics may result in additive or synergistic ototoxicity and/or nephrotoxicity.

CLINICAL EFFECTS: The combination of an aminoglycoside and a loop diuretic may increase risk for serious nephrotoxicity or ototoxicity.(1,2) Vestibular or auditory ototoxicity may be permanent.(1,3)

PREDISPOSING FACTORS: Preexisting renal impairment, extended duration of aminoglycoside therapy, greater than one aminoglycoside dose per day, rapid injection or high doses of loop diuretics, concomitant use of additional nephrotoxic agents such as iodinated contrast media or vancomycin, or sepsis appear to increase the risk for nephrotoxicity and ototoxicity.(1-6). Patients carrying certain variants in the MT-RNR1 gene (m.1555A>G, m.1095T>C, and m.1494C>T) are at increased risk of developing ototoxicity. An additional risk factor includes patients with a maternal relative known to have a clinically relevant MT-RNR1 variant. The risk of ototoxicity can occur at standard recommended doses of aminoglycosides.(7)

PATIENT MANAGEMENT: Administer aminoglycoside dosage every 24 to > 48 hours based upon renal function and continue therapy for less than 4 to 7 days, whenever possible.(4,5) The recommended maximal infusion rate for high dose furosemide therapy is 4 mg/minute.(2) When concurrent therapy is necessary monitor renal, hearing, and vestibular function. Signs of vestibular dysfunction include loss of balance and/or the visual sensation that stationary objects are moving (oscillopsia). In hospitalized or bedbound patients these symptoms may not be noticed or may be ascribed to other etiologies.(3)

DISCUSSION: Several studies and case reports have documented altered aminoglycoside levels, nephrotoxicity, and ototoxicity with concurrent therapy.(8-14) Otic aminoglycosides are included in this interaction because high aminoglycoside concentrations in the ear have been associated with an increased risk for hearing loss.

Aminoglycosides/Select Cephalosporins

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown.

CLINICAL EFFECTS: Nephrotoxicity may occur.

PREDISPOSING FACTORS: Preexisting renal impairment, older age, and large doses of either drug.

PATIENT MANAGEMENT: Try to avoid this combination in patients at risk of developing nephrotoxicity. Elderly patients, patients receiving large doses of either drug, and renal patients should be considered at risk. Monitor renal function if this combination is used.

DISCUSSION: This interaction is likely to occur in some patients, but clinical documentation is limited. This interaction is usually not a problem in patients with normal renal function.

Selected Nephrotoxic Agents/Cisplatin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The nephrotoxic effects of aminoglycosides or non-steroidal anti-inflammatory drugs (NSAIDs) may be additive to those of cisplatin.

CLINICAL EFFECTS: The concurrent administration of amikacin, gentamicin, tobramycin, or NSAIDs with cisplatin may result in additive nephrotoxic effects.(1,2,5,6)

PREDISPOSING FACTORS: Pre-existing renal insufficiency, advanced age, dehydration may increase the risk of nephrotoxicity.(1,5,6)

PATIENT MANAGEMENT: The US labeling for aminoglycosides and cisplatin states that the concurrent use of aminoglycosides and cisplatin should be avoided.(1,3,4,6) Inform patients that concurrent cisplatin and aminoglycosides or NSAIDs can cause nephrotoxicity and that renal function and electrolyte monitoring during treatment is necessary.(2)

DISCUSSION: The US manufacturers of amikacin, gentamicin and tobramycin state that since the nephrotoxic effects of these medications may be additive, avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic agents including cisplatin.(1,3,6)

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• Mt-RNr1 increased risk of aminoglycoside-induced hearing loss

• Clostridioides difficile infection
• Dehydration
• Disorder of the vestibulocochlear nerve
• Hypocalcemia
• Infant botulism
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Myasthenia gravis
• Pregnancy
• Tinnitus
• Vertigo

• Parkinsonism

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More Frequent

• Auditory neurotoxicity
• CNS toxicity
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Nephrotoxicity
• Ototoxicity
• Peripheral neuropathy

Less Frequent

• Allergic dermatitis
• Angioedema
• Erythema
• Optic neuritis
• Pruritus of skin
• Skin rash

Rare or Very Rare

• Neuromuscular blockade

There are no less severe adverse reactions for this drug.

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