Spectinomycin Chemical Properties

Melting point:

185 °C (decomp)

Boiling point:

583.1±50.0 °C(Predicted)

alpha 

D25 -20° (water)

Density 

1.43±0.1 g/cm3(Predicted)

pka

pKa1 6.95, pKa2 8.70(at 25℃)

EPA Substance Registry System

Spectinomycin (1695-77-8)

Spectinomycin Usage And Synthesis

Description

An unusual aminoglycoside antibiotic, spectinomycin is produced by fermentation of Streptomyces spectabil is and differs substantially in its clinical properties from the others. The diaminoinositol unit (spectinamine) contains two mono-N-methyl groups, and the hydroxyl between them has a stereochemistry opposite to that in streptomycin. The glycosidically attached sugar also is unusual in that it contains three consecutive carbonyl groups, either overt or masked, and is fused by two adjacent linkages to spectinamine to produce an unusual, fused, three-ring structure.

Originator

Trobicin,Upjohn,US,1971

Uses

Analogous to streptomycin, spectinomycin binds with ribosomal 30 S subunits of microorganisms and inhibits protein synthesis; however, incorrect reading of the genetic code does not take place. Despite the broad spectrum of activity, spectinomycin is used only for gonococci infections. Other Gram-negative bacteria begin to display resistance during treatment. It is effective with respect to most strains of gonococci, as well as a number of other Gram-negative microorganisms.
It is used for treating severe gonorrheal urethritis and proctitis in men, and severe gonorrheal proctitis in women, which is caused by strains of gonococci that are sensitive to the drug. Synonyms of this drug are actinospectocin, spectam, togamicin, and others.

Uses

Spectinomycin finds principal application in the treatment of gonorrhea. It should be noted that the antibiotic resistance among N. gonorrhoeae has caused a number of therapeutic problems. It has been found that only by escalating the antibiotic doses and using probenecid to retard the excretion of penicillin and ampicillin (the drugs of choice) has the continued effective use of penicillin, ampicillin, and tetracycline been possible. Even with modifications in the therapy, from 3 to 8% of cases fail to respond to the usual regimens for uncomplicated gonorrhea. Thus, the treatment of uncomplicated gonorrhea that fails to respond to the usual regimen is spectinomycin therapy.

Uses

Spectinomycin is an aminocyclitol antibiotic. It is used as a medicine in humans to treat Neisseria gonorrhoeae and is also used in veterinary medicine, especially in poultry, pigs and cattle. Cases of dermatitis have been reported in veterinary practice.

Definition

ChEBI: An organic heterotricyclic antibiotic that is active against gram-negative bacteria and used (as its dihydrochloride pentahydrate) to treat gonorrhea. It is produced by the bacterium Streptomyces spectabilis.

Manufacturing Process

A lyophilized culture of Streptomyces spectabilis, NRRL 2792, was used to seed the following sterile agar medium on tubed slants:Tryptone 5 K2HPO4 0.5 NaCl 0.5 FeSO4 0.1 Agar 20
Deionized water to make 1 liter
The slants were incubated for 7 days at 30°C, after which time sporulation was complete. The spores from the agar slants were used, in an aqueous suspension, to inoculate 100 ml of preseed medium in a 500 ml Erlenmeyer flask. The sterile preseed medium consisted of:
Grams Dried whole yeast 10 Glucose 10 Pancreatic digest of 5 casein (N-Z-Amine B)
Tap water to make 1 liter adjusted to pH 7.2 before sterilizing
The seed flash was incubated for 24 hours at 32°C on a reciprocating shaker after which it was used as an inoculum for a 20 liter seed fermenter in the amount of approximately 5%. the 20 liter seed fermenter contained a sterile medium consisting of:
Grams Glucose 15 Cornstarch 25 Distiller's solubles 15 Brewer's yeast 10 Corn steep liquor 20
Tap water to make 1 liter adjusted to pH 7.2 before sterilizing
The 20 liter seed fermenter was incubated for 24 hours at 32°C and aerated at the rate of 6 standard liters or about 0.2 standard cubic feet of air per minute and agitated with a sweep stirrer. The 20 liter seed fermenter was used to inoculate 250 liters of the same medium in a 100 gallon fermentation tank. 1,200 ml of lard oil were added during the fermentation to control foaming. The tank was agitated with a propeller and aerated at the rate of 75 standard liters of air per minute. After 96 hours of fermentation the beer assayed 500 mcg/ml (18.3 mcg/mg on a dry basis) of actinospectacin. Actinospectacin is assayed by its activity against Klebsiella pneumoniae by standard agar diffusion procedure and based on crystalline actinospectacin sulfate according to US Patent 3,234,092.

Therapeutic Function

Antibacterial

Antimicrobial activity

Its activity is modest and markedly affected by medium composition and pH. It exerts only moderate activity against Gram-positive organisms. It is widely active against enterobacteria, but Providencia spp. are resistant. Anaerobic bacteria are also resistant.
Of particular interest is its activity against N. gonorrhoeae, including β-lactamase-producing strains. Among other sexually acquired organisms, Ureaplasma urealyticum is susceptible, but Chlamydia trachomatis and T. pallidum are resistant.
For most organisms, the minimum bactericidal concentration (MBC) is at least four times the MIC and it is regarded as essentially bacteristatic. In contrast, it is bactericidal for gonococci at concentrations close to the MIC, which is of the order of 2–16 mg/L for both penicillin-susceptible and resistant strains.

Acquired resistance

N. gonorrhoeae strains resistant to spectinomycin have emerged in South East Asia, the USA and the UK; the resistance of UK isolates was not attributable to aminoglycoside-modifying enzymes. In most countries where its use remains low the prevalence of resistance in gonorrhea is also low.
Acquired resistance in enterobacteria, enterococci and staphylococci can be caused by nucleotidyltransferases that modify the drug at position 9. The enzyme from Gram-negative organisms ANT(3″) (9) also modifies streptomycin at position 3″, thus conferring cross-resistance to the two drugs. There is no enzymatic cross-resistance with 2-deoxystreptamine- containing aminoglycosides.

Contact allergens

Spectinomycin is an aminocyclitol antibiotic. It is used in human medicine against Neisseria gonorrhoeae and in veterinary medicine, especially for poultry, pigs, and cattle. Cases of dermatitis have been reported in veterinary practice.

Pharmacokinetics

C_{max 25 mg/kg intramuscular: 60–80 mg/L after 1 h
Plasma half-life: 2–3 h
Volume of distribution: 10–13.4 L
Plasma protein binding: <10%
It is poorly absorbed on oral administration. It is almost completely excreted unchanged in the urine over 48 h, concentrations on conventional dosage reaching 1 g/L. Excretion is prolonged in renal impairment, and is unaffected by probenecid.}

Clinical Use

Gonorrhea in penicillin-allergic patients or due to penicillin-resistant strains (single-dose treatment)

Side effects

Transient headache, dizziness, pain at the site of injection and occasional fever have been described. No evidence of ototoxicity or renal toxicity has been found in volunteers receiving doses of 2 g every 6 h for 3 weeks, amounts much in excess of those used therapeutically.

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