Спектиномицин

Описание

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.

Использование

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.

Определение

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.

Антимикробная активность

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.

Приобретенная устойчивость

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.

Контактные аллергены

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.

Фармакокине?тика

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.}

Клиническое использование

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

Побочные эффекты

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.