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At least 19 recordsLinked to original sources
PubMed1987

Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae.

Because of the high prevalence of penicillinase-producing Neisseria gonorrhoeae in the Republic of Korea, spectinomycin has been used there in the primary treatment of gonococcal infections in U.S. military personnel since 1981, but there have been increasingly frequent reports of treatment failures with spectinomycin. We conducted a clinical study to determine the efficacy of spectinomycin treatment in 124 U.S. servicemen in the Republic of Korea who had urethral gonococcal infections. Ninety-seven patients were treated with spectinomycin alone and evaluated in a follow-up visit. In eight patients (8.2 percent), this treatment was unsuccessful. Antibiotic-sensitivity testing on isolates from seven of the patients with treatment failure demonstrated that six isolates were highly resistant to spectinomycin (minimal inhibitory concentration, greater than or equal to 100 micrograms per milliliter). None of the spectinomycin-resistant strains had become resistant to penicillin, either through the production of penicillinase or through a chromosomal mutation. Although the mechanism of spectinomycin resistance appears to be a chromosomal mutation, these isolates were generally sensitive to other antibiotics. The prevalence of resistance to spectinomycin resulted in the substitution of ceftriaxone for the primary treatment of gonorrhea acquired by U.S. military personnel in the Republic of Korea. We believe that the rapid emergence of spectinomycin resistance in this population mandates a cautious approach to widescale use of the drug and indicates a need to broaden current surveillance programs.

Adolescent↗
PubMed1989

[Spectinomycin resistant gonococcal infections in West Germany. Detection in 7 patients and occurrence of post-gonorrheal epididymitis caused by the spectinomycin-resistant PPNG strain].

Seven patients (four men, three women) with gonococcal urethritis resistant to spectinomycin treatment were seen in May and June 1989 in the Department of Dermatology in Berlin (West), and strains of Neisseria gonorrhoeae (NG) resistant to spectinomycin were detected, cultured in vitro from these individuals. In five of the seven patients penicillin-resistant strains were found, including a penicillinase-producing strain in one case; the other two patients had penicillin-sensitive strains. In all cases the NG-populations detected were sensitive to cephalosporin and cipro(oxo)floxacin. In a 17-year-old young man with the PPNG strain severe gonococcal epididymitis developed after repeated infection that had been inadequately treated with spectinomycin. All seven patients mentioned sexual contact with individuals who lived in Southeast Asia or had their origins there; in at least four cases the contact persons came from Thailand. This is the first report on spectinomycin-resistant Neisseria gonorrhoeae infections (PPNG and non-PPNG) in the Federal Republic of Germany. The necessity for monitoring the results of penicillin and/or spectinomycin treatment of gonorrhoea are underlined for the dermatovenereologist, and some guidelines for therapy are given.

Adolescent↗
PubMed1988

Therapeutic efficacy of medicating drinking water with spectinomycin and lincomycin-spectinomycin in experimental Escherichia coli infection in poultry.

Although no microbiological activity was found in blood plasma during treatment of broilers through the drinking water with spectinomycin or lincomycin-spectinomycin, these drugs proved highly effective in treating experimentally induced colibacillosis. This efficacy may be produced by a metabolite or a degradation product of spectinomycin that reaches the infection site in the respiratory tract and interferes with adherence of bacteria.

Animals↗
PubMed1985

Spectinomycin modification. II. Spectinomycin C-3'-modification via diazoketone intermediates.

The C-3'-carbonyl group of N-protected spectinomycin is efficiently converted into a diazo group via base treatment of the corresponding tosylhydrazone. The diazo group imparts a new synthetically useful reactivity pattern on the sugar ring of the molecule. The synthesis of C-3'-deoxo-, monohalo- and dihalospectinomycins via the intermediacy of these diazo compounds is described. The reduced bioactivity of these analogs as compared to the parent and the C-3'-dihydro and aminospectinomycins established the need for hydrogen bonding groups in this region of the molecule for good activity, further refining the structure activity relationships in the spectinomycin series.

Chemical Phenomena↗
PubMed1985

Spectinomycin modification. III. Spectinomycin analogs with C-3'-branched chain sugars.

A variety of C-3'-branched chain analogs of spectinomycin has been synthesized via the intermediacy of spectinomycin derived diazoketones. In vitro antibacterial assay of these compounds has underscored the importance of hydrogen bonding functional groups in this region of the molecule. The most potent of these analogs had activity greater than or equal to the parent.

Carbohydrates↗
PubMed1988

Spectinomycin modification. IV. The synthesis of 3'-aminomethyldihydrospectinomycins via spectinomycin 3'-cyanohydrins.

The C-3'-carbonyl group of N-protected spectinomycin is converted into the corresponding aminomethylalcohols via the intermediacy of cyanohydrins. Methodology for the selective synthesis of either epimer with retention of protection in the aminocyclitol ring provides valuable synthetic intermediates for the preparation of analogs of this important antibiotic. The new methodology provides an efficient synthesis of the highly active 3'-aminomethyldihydrospectinomycins.

Chemical Phenomena↗
PubMed1988

Spectinomycin modification. V. The synthesis and biological activity of spectinomycin analogs with ring-expanded sugars.

Tiffeneau-Demjanov rearrangement of 3'-(R)-N,N'-dibenzyloxycarbonyl-3'-aminomethyl-dihydrospectinom ycin results in ring expansion affording the homologous analog with a seven-membered sugar ring. In stark contrast, attempted rearrangement of the 3'-S-isomer leads only to epoxide formation. Deprotection of the ring-expanded homolog gives homospectinomycin. The synthesis and biological activity of this interesting new member of the spectinomycin series and the derived dihydrohomospectinomycin is detailed in this paper.

Chemical Phenomena↗
PubMed1985

Derivatization of secondary amines with 2-naphthalene-sulfonyl chloride for high-performance liquid chromatographic analysis of spectinomycin.

A normal-phase high-performance liquid chromatographic (HPLC) method has been developed for the assay of spectinomycin hydrochloride and spectinomycin sulfate for detection at 254 nm. The method involves pre-column derivatization of secondary amines of spectinomycin with 2-naphthalenesulfonyl chloride (NSCl) using a catalyst. Lincomycin, 1-methylpyrrole, 2-acetyl-1-methylpyrrole, and 2-acetyl-pyrrole act as catalysts for sulfonylation of spectinomycin. Without a catalyst, the derivatization reaction forms a considerable amount of actinospectinoic acid, a degradation compound of spectinomycin, and peak area:weight ratio of the derivative is approximately 15% lower than those with the catalyst. Following derivatization the sample is extracted and chromatographed on a normal-phase silica column with detection at 254 nm. The method is applicable for the analysis of both the hydrochloride and sulfate salt forms of spectinomycin. All the known degradation compounds of spectinomycin such as actinamine, actinospectinoic acid and the biosynthesis intermediates, dihydrospectinomycin diastereoisomers, are completely separated with this method. Mass spectrometric data confirms that spectinomycin is derivatized with NSCl at the secondary amines located at positions 6 and 8 of the ring structure. The standard curves for the HPLC assay of spectinomycin hydrochloride and sulfate are linear with correlation coefficients of 0.9997 and 0.9999, respectively over the range of 0.05 mg/ml to 0.3 mg/ml. The relative standard deviations (R.S.D.) of the HPLC assay methods for spectinomycin hydrochloride and sulfate are 0.67% and 0.86%, respectively. Spectinomycin hydrochloride and sulfate bulk drugs were assayed by the HPLC method and compared to gas-liquid chromatography and microbiological assay results. The HPLC method was used to assay spectinomycin in a veterinary formulation, Linco-Spectin soluble powder. The sensitivity of the HPLC assay was determined to be approximately 4 ng sample load on the column, which suggests applicability in serum and residue level studies.

Amines↗
PubMed1979

Spectinomycin-resistant mutants of Bacillus subtilis with altered sporulation properties.

Spectinomycin-resistant mutants of Bacillus subtilis show three different types of alterations in sporulation ability. Class 1 mutants can both grow and sporulate in the presence of spectinomycin. Class 2 mutants can grow in the presence of spectinomycin, but are unable to sporulate in either the presence or absence of spectinomycin. Class 3 mutants have a conditional phenotype, and are able to sporulate in the absence of spectinomycin, but not in its presence. The ability of these strains to produce alkaline phosphatase, a biochemical marker for early sporulation events, is correlated with the ability to sporulate in the presence or absence of antibiotic. All of the spectinomycin-resistance mutations could be genetically linked to the cysA marker, and a mutational alteration of a protein of the 30S ribosomal subunit has been identified in one of the Class 3 strains (Spc 1-11). Fine-structure mapping of the spectinomycin resistance mutation of strain Spc 1-11 confirmed its location in the cluster of genes for ribosomal components on the B. subtilis genetic map. Genetic analysis indicated that the properties of the Class 1 and Class 2 mutants result from more than one mutation. The spectinomycin-resistance and altered sporulation properties of the two Class 3 mutants probably result from a single genetic lesion.

Bacillus subtilis↗
PubMed1976

[Ototoxicity of spectinomycin (author's transl)].

Spectinomycin is an aminocyclitol antibiotic, but different in chemical structure from other aminocyclitol antibiotics such as streptomycin, kanamycin and gentamicin. Spectinomycin clinically has been proven to be highly effective in the intramuscular single-dose treatment of gonorrhea. According to NOVAK et al. (1974), all evidence from pharmacological and clinical efficacy studies to date indicates that spectinomycin is free from ototoxic effects at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) or repeated i.m. or i.v. doses, 8g/day. The present experimental study has been made to evaluate the ontoxocic effects of spectinomycin in Hartley strain guinea pigs given i.m. a single-high dose (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) respectively. Differential frequency pinna reflex test in frequency range from 20 KHz to 500 Hz revealed that no animals showed disappearance of pinna reflex in the frequencies tested. Histologic examination in serial celloidin sections of the cochlea and vestibulum disclosed that a few animals given a single-high dose of spectinomycin (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose or spectinomycin (80 mg/kg daily for 4 weeks) respectively showed limited mild damage of outer hair cells in the spiral organ and of hair cells in the vestibular organ. There were histologically a few focal necrosis in the liver and scattered interstitial cell infiltration around the proximal convoluted tubules which are lined with regenerated epithelial cells in some animals given the single-high dose (800 mg/kg or 1,600 mg/kg) or repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) of spectinomycin. Positive correlation between the extent of the hair cell damage and the injury of the liver and kidney was not confirmed. The present study suggests that administration of spectinomycin at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) most probably is free from ototoxic effect.

Animals↗
PubMed1988

In vitro antibacterial activity of trospectomycin (U-63366F), a novel spectinomycin analog.

Trospectomycin (U-63366F) is a novel spectinomycin analog with broad-spectrum antibacterial activity. The in vitro activity of this analog was compared with that of spectinomycin and other reference antibiotics against 411 clinical isolates of aerobic and anaerobic bacteria. MICs were determined by agar or broth dilution methods. The stability of trospectomycin in the presence of an enzyme extract derived from spectinomycin-resistant Escherichia coli was determined. Trospectomycin was more active than spectinomycin (4- to 32-fold) against strains of numerous bacterial species, including staphylococci, streptococci, Haemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Proteus species, Bacteroides species, Clostridium difficile, Clostridium species, and Chlamydia trachomatis. Trospectomycin demonstrated a moderate level of activity (comparable to that of spectinomycin) for most species of the family Enterobacteriaceae tested and was generally cross resistant with spectinomycin. Trospectomycin was susceptible to inactivation by crude enzyme preparations from spectinomycin-inactivating strains of E. coli. Trospectomycin inhibited a variety of clinically important organisms, including agents of sexually transmitted diseases and pelvic inflammatory disease. Clinical studies with this novel aminocyclitol antibiotic are in progress.

Anti-Bacterial Agents↗
PubMed1987

Spectinomycin resistance and associated DNA amplification in Streptomyces achromogenes subsp. rubradiris.

Streptomyces achromogenes subsp. rubradiris plated at low density on 1,000 micrograms of spectinomycin per ml initially produces slow-growing, bald colonies from which arise, in a spatially and temporally random fashion, foci of rapidly growing aerial mycelium-forming cells whose DNA contains an approximately 200- to 300-fold amplification of an 8-kilobase (kb) sequence. This sequence was cloned in Escherichia coli on pBR322 and physically characterized. It was separately cloned also in Streptomyces lividans as a BglII fragment and shown to impart high-level resistance to spectinomycin in an orientation-independent manner when present in either the high-copy-number vector pIJ702 or the unit-copy-number vector pIJ943. A spectinomycin resistance determinant was shown to reside on a 1.7-kb SphI-BglII subfragment. Analysis of Southern blots of restriction enzyme digests of wild-type S. achromogenes DNA probed with the labeled 8-kb DNA sequence resulted in the identification and subsequent cloning in S. lividans of a 10.4-kb BamHI fragment which probably includes the complete 8.8-kb amplifiable unit of DNA. This unit is present in wild-type S. achromogenes and in the initially slow-growing, bald colonies arising on 1,000 micrograms of spectinomycin per ml as a single copy. It carries two 0.8-kb direct repeats at its termini as well as the spectinomycin resistance determinant close to one of these termini. About 5% of protoplast regenerants from wild-type S. achromogenes and 77% of protoplast regenerants from the rapidly growing strains lost both the ability to grow on spectinomycin at 10 micrograms/ml and the sequences that hybridize with the 8-kb probe DNA. The 1.7-kb Bg/II-SphI resistance fragment, when introduced via the vector pIJ702 into an S. achromogenes strain sensitive to 10 microgram of spectinomycin per ml, permitted its vigorous growth on 1,000 micrograms of the antibiotic per ml.

Chromosome Mapping↗
PubMed1985

Testing sensitivity of Neisseria gonorrhoeae to spectinomycin.

A concentration of 16 mg/l spectinomycin incorporated in agar gave the best discrimination between Neisseria gonorrhoeae sensitive and resistant to spectinomycin. This method was compared with spectinomycin sensitivity testing with 25 micrograms or 100 micrograms discs. Both methods agreed fully for 197 spectinomycin sensitive and three spectinomycin resistant gonococci. The agar incorporation "breakpoint" concentration technique failed to detect a small spectinomycin resistant population in a fourth isolate, which was detected by disc testing. It may be possible to predict the emergence of spectinomycin resistance among strains of N gonorrhoeae.

Microbial Sensitivity Tests↗
PubMed1976

[In vitro antibacterial effects of spectinomycin and penicillin G on Neisseria gonorrhoeae singly and in combination (author's transl)].

The antibacterial effects of spectinomycin and penicillin G on clinical isolates of Neisseria gonorrhoeae were studied. The concentrations of penicillin G at which the isolates showed drug sensitivity ranged widely from 0.011 to 6.25 mug/ml. Some of the isolates were resistant to penicillin G. Sensitivity to spectinomycin was observed at the drug concentrations ranging from 3.13 to 12.5 mug/ml. About 60% of the isolates were sensitive to 6.25 mug/ml of spectinomycin, and those isolates which were resistant to penicillin G showed good sensitivity to spectinomycin. No correlation in sensitivity was noted between the two drugs. Tests for their bactericidal activities on bouillon media revealed that the addition of spectinomycin at the concentration of 12.5 mug/ml or over produced a marked bactericidal effect in a short time while penicillin G exhibited a bactericidal or bacteriostatic effect depending upon the concentration used. A synergistic effect of a penicillin and an aminoglycoside antibiotic was observed in these isolates of N. gonorrhoea as was in the isolates of Pseudomonas aeruginosa. Where penicillin G and spectinomycin were used in combination, a simultaneous addition of both the drugs produced the most marked synergistic effect. Morphology of N. gonorrhoeae cells exposed to either of these drugs was examined under a scanning electron microscope. Exposure to spectinomycin at the level of 6.25 mug/ml resulted in almost no morphological change. At 6.25 mug/ml of the drug, however, a roughened cell surface, a bleb-like structure or a state suggesting the loosening of such a bleb-like structure was noted. The addition of penicillin G at 0.19 mug/ml led to an impairment of cell division at one hour of exposure and to cell swelling and lysis with further exposure. At 1.19 mug/ml of the drug, these processes of cell swelling and lysis took place early.

Drug Combinations↗
PubMed1977

A spectinomycin dependent mutant of Escherichia coli.

A mutant of Escherichia coli B has been isolated which shows a novel phenotype of spectinomycin dependence. The mutant, termed RD, needs spectinomycin to grow at temperatures of 37 degrees or below; it is unable to grow at 42 degrees in either the presence or absence of spectinomycin. Secondary mutants which grow well in the absence of spectinomycin can be isolated spontaneously at a frequency of about 10(-6). Two-dimensional gel electrophoresis of ribosomal proteins from 25 of these revertants showed that two revertants had an alteration in S4; one other showed an alteration in L5, and one showed an apparent absence of L1. Mutant RD itself had an altered less basic S5, which was maintained in all the revertants that were checked. Genetic analysis indicated that RD was a double mutant: one mutation, which alone conferred a spectinomycin resistant phenotype on the strain, was located in the strA region of the E. coli chromosome and was represented by the mutation in S5. The other mutation, which conferred the dependence on spectinomycin, mapped close to the rif locus.

Escherichia coli↗
PubMed1977

Spectinomycin versus tetracycline for the treatment of gonorrhea.

Spectinomycin and tetracycline are alternative drugs to penicillin in the treatment of gonorrhea. To compare the efficacy of these agents and their propensity to select resistant gonococci, we treated 4043 patients randomly with either 2 or 4 g of spectinomycin once or 9 g of oral tetracycline for four days. Minimum cure rate for anogenital gonorrhea was 94 per cent with either drug. Oropharyngeal infection responded poorly to spectinomycin in men, with failure of therapy in six of 11. Postgonococcal urethritis in men was less common after tetracycline than after spectinomycin (P less than 0.005). Spectinomycin failure was not related to drug resistance. Tetracycline failure correlated with resistance (P less than 0.0002); one fifth of the isolates resistant to 1.0 mug per milliter of tetracycline were not eradicated. For several reasons, including the appearance of beta-lactamase-producing gonococci, it is no longer clear that penicillin G is the "drug of choice" for gonorrhea. Spectinomycin and tetracycline are equally acceptable alternatives, each with distinct advantages and disadvantages.

Administration, Oral↗