Spectinomycin is an aminocyclitol antibiotic.
Uses
Gonorrhea and Associated Infections
Spectinomycin is used in the treatment of uncomplicated cervical, urethral, or rectal gonorrhea caused by susceptible Neisseria gonorrhoeae and also is used in the treatment of disseminated gonococcal infections. Although not considered a drug of choice for the treatment of gonococcal infections, spectinomycin is considered a useful alternative for the treatment of gonococcal infections in patients who are hypersensitive to or cannot tolerate cephalosporins and fluoroquinolones. The drug also is an effective alternative for the treatment of gonorrhea in pregnant women and children when fluoroquinolones are contraindicated and cephalosporins cannot be used. Compared with other regimens available for the treatment of gonorrhea, spectinomycin has the disadvantages of being relatively expensive and requiring parenteral administration.
Uncomplicated Cervical, Urethral, and Rectal Gonorrhea
The US Centers for Disease Control and Prevention (CDC) recommends that uncomplicated cervical, urethral, or rectal gonorrhea in adults and adolescents be treated with a single IM dose of ceftriaxone. a single oral dose of cefixime, or a single oral dose of certain fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) given in conjunction with an anti-infective regimen effective for presumptive treatment of chlamydia (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline). However, fluoroquinolones should not be used for the treatment of gonorrhea acquired in Asia or the pacific islands (including Hawaii) and may be inadvisable for infections acquired in other areas where N. gonorrhoeae with quinolone resistance have been reported (including California).
Alternative regimens recommended by the CDC for the treatment of uncomplicated cervical, urethral, or rectal gonorrhea in adults and adolescents include a single IM dose of spectinomycin, a single IM dose of certain cephalosporins (cefotaxime, cefoxitin, ceftizoxime), or a single oral dose of certain fluoroquinolones (gatifloxacin, lomefloxacin, norfloxacin) given in conjunction with an anti-infective regimen effective for presumptive treatment of chlamydia. In published clinical studies in adults with urogenital and anorectal gonococcal infections, the cure rate reported for spectinomycin has been 98.2%.
Although IM ceftriaxone is considered the treatment of choice for uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, proctitis, or pharyngitis in children weighing less than 45 kg, the CDC and American Academy of Pediatrics (AAP) state that a single IM dose of spectinomycin can be used for the treatment of uncomplicated cervical, urethral, or rectal gonorrhea in children who cannot tolerate cephalosporins.
Uncomplicated Pharyngeal Gonorrhea
Although spectinomycin is effective in the treatment of urethral, cervical, and anorectal gonococcal infections, the drug may be ineffective in the treatment of pharyngeal gonococcal infections. The CDC states that spectinomycin is unreliable (only 52% effective) for the treatment of pharyngeal gonorrhea; therefore, if the drug is used for the treatment of gonorrhea in adults, adolescents, or children known or suspected to have pharyngeal infection, pharyngeal cultures should be evaluated 3-5 days after treatment to verify eradication of the infection.
Disseminated Gonococcal Infections
Spectinomycin is used as an alternative agent for the treatment of disseminated gonococcal infections. The CDC recommends that treatment of disseminated gonococcal infections in adults and adolescents be initiated with a multiple-dose regimen of IM or IV ceftriaxone. Alternatively, the CDC recommends a multiple-dose regimen of certain IV cephalosporins (cefotaxime, ceftizoxime), certain IV fluoroquinolones (ciprofloxacin, levofloxacin), or IM spectinomycin for the initial treatment of disseminated gonococcal infections in adults and adolescents.
The initial parenteral regimen should be continued for 24-48 hours after improvement begins; therapy can then be switched to oral cefixime, oral ciprofloxacin, oral ofloxacin, or oral levofloxacin and continued to complete at least 1 week of therapy. Unless the presence of coexisting chlamydial infection has been excluded by appropriate testing, individuals being treated for disseminated gonococcal infections also should receive an anti-infective regimen effective for presumptive treatment of chlamydia. The CDC recommends that the patient be hospitalized for initial treatment of disseminated gonorrhea, especially when compliance may be a problem, when the diagnosis is uncertain, or when the patient has purulent synovial effusions or other complications.
Patients should be examined for clinical evidence of endocarditis and meningitis; the recommended regimen for these infections is IV ceftriaxone. For additional information on current recommendations for the treatment of gonorrhea and associated infections.
Dosage and Administration
Reconstitution and Administration
Spectinomycin hydrochloride is administered by deep IM injection into the upper outer quadrant of the gluteal muscle using a 20-gauge needle. Vials labeled as containing 2 g of spectinomycin are reconstituted by adding 3.2 mL of bacteriostatic water for injection containing 0.945% benzyl alcohol. The resulting suspensions contain 400 mg of spectinomycin per mL. After adding the diluent and prior to withdrawing the dose, the vial containing the suspension should be shaken vigorously.
Dosage
Dosage of spectinomycin hydrochloride is expressed in terms of spectinomycin.
Uncomplicated Cervical, Urethral, and Rectal Gonorrhea
When spectinomycin is used for the treatment of uncomplicated cervical, urethral, or rectal gonorrhea, adults and adolescents should receive a single 2-g IM dose. The manufacturer states that a single 4-g IM dose may be preferred for the treatment of uncomplicated gonorrhea in geographic areas where resistance is known to be prevalent; the dose can be divided and given into 2 different gluteal injection sites. Although safety and efficacy of spectinomycin in children has not been definitely established, the US Centers for Disease Control and Prevention (CDC) and American Academy of Pediatrics (AAP) state that uncomplicated cervical, urethral, and rectal gonorrhea in children weighing less than 45 kg can be treated with spectinomycin given as a single IM dose of 40 mg/kg (maximum 2 g). Children weighing 45 kg or more may receive the recommended adult dosage.
Disseminated Gonococcal Infections
When used for the treatment of disseminated gonococcal infections, the CDC recommends that adults and adolescents receive 2 g of spectinomycin IM every 12 hours; parenteral therapy should be continued for 24-48 hours after improvement begins and can then be switched to an oral regimen (cefixime, ciprofloxacin, ofloxacin, levofloxacin) to complete at least week of therapy.
Cautions
Adverse Effects
Spectinomycin usually is well tolerated and appears to have a low order of toxicity; the most frequent adverse effect is pain at the injection site. Adverse effects reported following single doses of the drug include soreness at the injection site, urticaria, transient rash, pruritus, dizziness, headache, nausea, vomiting, chills, fever, nervousness, and insomnia. Anaphylaxis or anaphylactoid reactions have been reported rarely with spectinomycin.
Serious hypersensitivity reactions should be treated with appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated. Decreases in hemoglobin, and creatinine clearance and increases in BUN, ALT (SGPT), and serum alkaline phosphatase have been reported rarely in healthy individuals following multiple-dose subchronic tolerance studies.
Rarely, a reduction in urine output has occurred in healthy individuals in both single- and multiple-dose studies. However, the manufacturer states that extensive renal function studies in patients receiving spectinomycin have demonstrated no consistent changes indicative of renal toxicity.
Precautions and Contraindications
Since spectinomycin is ineffective in the treatment of syphilis and may mask or delay symptoms of incubating syphilis, all patients being treated for gonorrhea with spectinomycin should receive a serologic test for syphilis at the time of diagnosis and 3 months later. Spectinomycin should be administered with caution in patients with a history of allergies and is contraindicated in patients who are hypersensitive to the drug.
Pediatric Precautions
Although safety and efficacy of spectinomycin have not been established in pediatric patients, the CDC and American Academy of Pediatrics (AAP) recommend that spectinomycin be used for the treatment of gonococcal infections in children hypersensitive to cephalosporins. Spectinomycin powder for injection is reconstituted with bacteriostatic water for injection containing benzyl alcohol.
Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., 100-400 mg/kg daily) of benzyl alcohol in these neonates. Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the AAP states that presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates.
Mutagenicity and Carcinogenicity
Spectinomycin was not mutagenic or genotoxic in Ames tests, micronucleus tests in mice, unscheduled DNA synthesis tests in rat primary hepatocytes, or a chromosomal aberration test in Chinese hamster ovary cells.
Pregnancy, Fertitlity and Lactation
Spectinomycin was not teratogenic or embryocidal when given orally or subcutaneously to rats at dosages of 300 mg/kg daily (equivalent to the maximum recommended human dosage based on mg/m2). There also was no evidence of teratogenicity when the drug was given intraperitoneally to mice or rats at dosages of 400 or 1600 mg/kg daily, respectively, and embryonic and fetal development were unaffected when spectinomycin was administered IM or subcutaneously to pregnant rabbits at dosages up to 300 mg/kg daily (equivalent to the maximum recommended human dosage based on mg/m2).
Although safe use of spectinomycin during pregnancy has not been definitely established, the CDC and other clinicians state that the drug can be used for the treatment of gonorrhea in pregnant women who are hypersensitive to cephalosporins. There was no adverse effect on fertility or general reproductive performance when spectinomycin was administered subcutaneously to rats at dosages up to 300 mg/kg (equivalent to the maximum recommended human dosage based on mg/m2).
Results of a 3-generation reproduction study in rats that received spectinomycin hydrochloride orally at dosages up to 400 mg/kg (equivalent to the maximum recommended human dosage based on mg/m2) did not reveal evidence of any drug-induced toxicity during growth, gestation, or lactation periods in any of the generations, although pregnancy rates in the group receiving 400 mg/kg daily were consistently lower than those in the control group.
Histopathology examinations of the testes and ovaries of the third generation animals were normal. It is not known whether spectinomycin is distributed into milk. Because many drugs are distributed into milk, spectinomycin should be used with caution in nursing women.
Acute Toxcicity
The manufacturer states that information on overdosage of spectinomycin is not available. Hemodialysis has been reported to aid in the removal of intravenously administered spectinomycin.
Mechanism of Action
Spectinomycin is usually bacteriostatic in action and appears to inhibit protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits. Spectrum In general, spectinomycin has a variable degree of activity in vitro against a wide variety of gram-positive and gram-negative bacteria. Spectinomycin is inactive against Treponema pallidum or Chlamydia trachomatis. In vitro, spectinomycin concentrations of 1-20 mcg/mL inhibit most of penicillinase-producing and nonpenicillinase-producing strains of Neisseria gonorrhoeae.
In Vitro Susceptibility Testing
When the disk-diffusion procedure is used to test in vitro susceptibility of N. gonorrhoeae, the National Committee for Clinical Laboratory Standards (NCCLS) states that a disk containing 100 mcg of spectinomycin should be used.
When the disk-diffusion procedure is performed according to NCCLS standardized procedures using GC agar base (with 1% defined growth supplement), N. gonorrhoeae with growth inhibition zones of 18 mm or greater are susceptible to spectinomycin, those with zones of 15-17 mm have intermediate susceptibility, and those with zones of 14 mm or less are resistant to the drug.
When NCCLS standardized procedure for broth dilution is performed using GC agar base (with 1% defined growth supplement), N. gonorrhoeae with MICs of 32 mcg/mL or less are susceptible to spectinomycin, those with MICs of 64 mcg/mL have intermediate susceptibility, and those with MICs of 128 mcg/mL or greater are resistant to the drug.
Resistance
Resistance to spectinomycin has been induced in vitro, and spectinomycin-resistant strains of penicillinase-producing Neisseria gonorrhoeae (PPNG) and nonpenicillinase-producing N. gonorrhoeae have been reported. Resistance to spectinomycin is relatively uncommon, and the drug has been active against most strains of N. gonorrhoeae resistant to fluoroquinolones. The exact mechanism(s) of spectinomycin resistance has not been clearly established, but several studies suggest it may result from a ribosomal alteration.
Pharmacokinetics
Absorption
Spectinomycin hydrochloride is not absorbed from the GI tract; however, the drug is rapidly absorbed following IM administration. Following IM administration of a single 2-g dose of spectinomycin in adults with normal renal function, peak serum spectinomycin concentrations averaging about 100 mcg/mL are reached at 1 hour and serum concentrations of the drug average 15 mcg/mL at 8 hours. When a single 4-g IM dose is administered, peak plasma concentrations average 160 mcg/mL at 2 hours and serum concentrations average 31 mcg/mL at 8 hours.
Distribution
It is not known if spectinomycin crosses the placenta or is distributed into milk in humans. The drug is not substantially bound to plasma proteins.
Elimination
The plasma half-life of spectinomycin is reported to be 1.2-2.8 hours in adults. Within 48 hours, 70-100% of a single IM dose of spectinomycin is excreted in the urine by glomerular filtration as spectinomycin or a microbiologically active metabolite. The manufacturer states that hemodialysis has been reported to aid in the removal of intravenously administered spectinomycin.
Chemistry and Stability
Chemistry
Spectinomycin is an aminocyclitol antibiotic obtained from cultures of Streptomyces spectabilis. The drug is commercially available as the dihydrochloride pentahydrate that occurs as a white to pale buff, crystalline powder and is freely soluble in water and practically insoluble in alcohol. Spectinomycin has pKas of 7 and 8.7. Following reconstitution with bacteriostatic water for injection containing 0.945% benzyl alcohol, spectinomycin hydrochloride injection has a pH of 4-7.
Stability
Commercially available spectinomycin hydrochloride powder for injection should be stored at 20-25°C. Following reconstitution with bacteriostatic water for injection containing 0.945% benzyl alcohol, spectinomycin hydrochloride injection should be stored at 20-25°C and used within 24 hours.
Preparations
Spectinomycin Hydrochloride Parenteral For injection, for 2 g (of spectinomycin) Trobicin®, (with IM use only bacteriostatic water for Cefditoren pivoxil is a semi-synthetic third-generation cephalosporin. injection diluent containing benzyl alcohol 0.945%) Pfizer