Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Spectinomycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Spectinomycin inhibits the self-splicing of the group 1 intron RNA.

Effects of the aminoglycoside spectinomycin on the self-splicing of primary transcripts of the phage T4 thymidylate synthase gene (td) have been investigated. The kinetic analysis demonstrated that spectinomycin acts as a mixed noncompetitive inhibitor for the td intron RNA with a K(i) of 7.2 mM. Increasing the spectinomycin concentration raised the K(m) values with the corresponding decrease of V(max) and k(cat) values. The specificity of the splicing inhibition by spectinomycin is due to changes in both K(m) and k(cat). The splicing inhibition by spectinomycin is dependent on pH changes and Mg(2+) concentration, indicating electrostatic interactions with the intron RNA. It has been proposed that the key structural features in spectinomycin responsible for the inhibition of splicing may be the hydroxyl groups on the antibiotic.

Guanosine Triphosphate↗
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↗
PubMed2000

K(+) and Mg(2+) ions promote the self-splicing of the td intron RNA inhibited by spectinomycin.

The effects of Mg(2+) and K(+) ions on the self-splicing inhibition of the td (thymidylate synthase gene) intron RNA by spectinomycin were investigated. The maximum splicing activity occurred at 20 mM KCl. The K(m) and V(max) values for GTP in the presence of 5 mM Mg(2+) are 2.25 microM and 0.55 min(-1), whereas those for GTP both in the presence of 5 mM Mg(2+) and 5 mM K(+) are 1.23 microM and 0. 46 min(-1), respectively. Spectinomycin at 10 mM concentration inhibited the splicing by about 10%, but at 20 mM concentration, the splicing rate was inhibited by about 63%. The splicing inhibition by the low concentration of spectinomycin was overcome markedly as the concentration of Mg(2+) ion was raised. At 30 mM spectinomycin, however, the splicing inhibition was not significantly affected by increasing the concentration of Mg(2+). A similar activation of the splicing rate was observed as the concentration of K(+) ion was increased. The concentration of K(+) ion required for the normal recovery of the splicing was much higher than that of Mg(2+) ion. Unlike Mg(2+) ion, 30 mM K(+) ion effectively alleviated the splicing inhibition by spectinomycin at its high concentration. The results indicate that K(+) and Mg(2+) ions may show mechanistically different interactions with spectinomycin in the self-splicing reaction of the td intron RNA.

Animals↗
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↗
PubMedDate not supplied

Evaluation of spectinomycin and gentamicin in the treatment of hospitalized patients with resistant urinary tract infections.

Spectinomycin hydrochloride 140 mg/kg/day and gentamicin 3 mg/kg/day were evaluated in the treatment of 50 hospitalized patients with urinary tract infections. Seven patients (28%) in the spectinomycin group had positive urine cultures after 72 hours of therapy due to initial resistance of the organism (5 isolates) or development of resistance to spectinomycin (2 isolates). Response to gentamicin therapy was uniformly satisfactory. Complications of spectinomycin therapy included pain and induration at the injection site (11 patients) and elevated serum creatinine values (2 patients). Ototoxicity was noted in three patients given gentamicin. Peak serum concentrations of spectinomycin (range 55-157 microgram/ml) and gentamicin (range 2.8--8.5 microgram/ml) showed marked interpatient variation. Spectinomycin appears to be of limited value in the treatment of urinary tract infections caused by gram-negative bacilli.

Adult↗
PubMedDate not supplied

Treatment of chancroid with a single dose of spectinomycin.

Fifty patients with lesions characteristic of chancroid were enrolled in an open-label prospective study to examine the efficacy of a single 2-gm dose of spectinomycin for treatment of chancroid. Only those patients (41 men; aged 18 to 49 years) with positive culture results for Haemophilus ducreyi were included in the analysis. Patients each received a single 2-gm dose of spectinomycin intramuscularly. The recovery process began on the third day of follow-up, as evidenced by the occurrence of epithelialization and a decrease in inflammation. By the seventh day after treatment, only one patient had ulcers; 40 patients experienced eradication of all ulcers (P less than 0.0001). The condition of nodes affected by infection also indicated efficacy of treatment (P less than 0.01); only one patient still had a swollen node by the fourteenth day after treatment. Of the 41 patients, 37 (90%) had negative culture results for H. ducreyi on the third day after treatment. Only 4 patients (10%) required a second dose of spectinomycin on the seventh day to affect a cure. Treatment with spectinomycin resulted in a 98% cure rate 14 days after treatment. The minimum inhibitory concentration (MIC) of spectinomycin was 1 microgram/mL to 3 micrograms/mL in the 15 strains studied. The drug was well tolerated and no adverse reactions were reported. It is concluded that a single 2-gm dose of spectinomycin is a safe and effective alternative drug for treatment of chancroid.

Adolescent↗
PubMed1976

Coordinated alterations in ribosomes and cytoplasmic membrane in sucrose-dependent, spectinomycin-resistant mutants of Escherichia coli.

Alterations in cytoplasmic membrane and ribosomes from sucrose-dependent spectinomycin-resistant (Sucd-Spcr) mutants of Escherichia coli, mutants that are resistant to spectinomycin in the presence of 20% sucrose but sensitive in the absence of sucrose, were studied. The protein composition of cytoplasmic membrane was analyzed by gel electrophoresis on polyacrylamide gel containing 8 M urea and 0.5% sodium dodecyl sulfate, which assured the reproducible separation of 28 protein bands. A major protein band, I-19, was missing in all cytoplasmic membrane preparations from 10 Sucd-Spcr mutants. Besides protein I-19, proteins I-13 and I-24 were missing in some mutants. On the other hand, the protein composition of cytoplasmic membrane from a sucrose-independent spectinomycin-resistant mutant was indistinguishable from that from the wild-type strain. The polypeptide synthetic activity of ribosomes from Sucd-Spcr mutants was resistant to spectinomycin. Studies on a revertant obtained from one of these mutants without any selection for sensitivity to spectinomycin revealed that a single mutation was responsible for both the ribosomal alteration, i.e., spectinomycin resistance, and the lack of protein I-19 in the cytoplasmic membrane. Studies on a transductant obtained with a Sucd-SPcr mutant as the donor also confirmed the single-mutation concept. It was concluded that in Sucd-SPcr mutants an alteration in the ribosomes caused the deletion of protein I-19 from cytoplasmic membrane.

Bacterial Proteins↗
PubMed1988

Single dose oral norfloxacin or intramuscular spectinomycin to treat gonorrhoea (PPNG and non-PPNG infections): analysis of efficacy and patient preference.

Norfloxacin, a new oral quinolone, was compared with intramuscular spectinomycin for treating culture proved gonorrhoea (caused by penicillinase producing strains of Neisseria gonorrhoeae (PPNG) and non-PPNG strains. A total of 547 infected men and women were randomly allocated to treatment with either single dose norfloxacin (800 mg by mouth) or spectinomycin (2 g intramuscularly). Patient preference for tablets or injections was noted at this visit. Patients returned four to eight days later for assessment of efficacy, safety, and preference. Of the 482 patients who attended follow up, all those treated with norfloxacin (94 infected with PPNG strains, 145 with non-PPNG strains) and all 82 infected with PPNG strains and treated with spectinomycin were cured. Of 161 infected with non-PPNG strains and treated with spectinomycin, 159 (99%) were cured. Side effects (headache, nausea, and sleepiness) occurred in three patients receiving norfloxacin and in 17 (16 pain at injection site, 1 giddiness) receiving spectinomycin. Most patients preferred tablets to injection both on day 1 (313 v 200) and at follow up (373 v 104). This study showed that norfloxacin was a highly effective alternative to spectinomycin, produced fewer side effects, and was the preferred mode of administration.

Administration, Oral↗
PubMed2002

Isolation of spectinomycin resistance mutations in the 16S rRNA of Salmonella enterica serovar Typhimurium and expression in Escherichia coli and Salmonella.

Two single-base mutations in 16S rRNA conferring high-level resistance to spectinomycin were isolated on a plasmid-borne copy of the rrnD operon from Salmonella enterica serovar Typhimurium. Neither of the mutations (C1066U and C1192U) had appreciable effects on cell growth, but each had differential effects on resistance to spectinomycin and fusidic acid. Both mutations also conferred resistance to spectinomycin in Escherichia coli strains containing deletions of all seven chromosomal rrn operons and expressing plasmid-encoded Salmonella rRNA exclusively. In contrast, when expressed in E. coli strains containing intact chromosomal rrn operons, the strains were sensitive to spectinomycin. However, chromosomal mutations arose that allowed expression of the rRNA-dependent spectinomycin resistance phenotype. It is proposed that in heterogeneous rRNA populations, the native E. coli rRNA out-competes the heterologous Salmonella rRNA for binding to ribosomal proteins, translation factors, or ribosome assembly, thus limiting entry of the antibiotic-resistant 30S subunits into the functioning ribosome pool.

Anti-Bacterial Agents↗
PubMedDate not supplied

Penicillin and spectinomycin in treatment of gonococcal urethritis.

In view of the recent discovery of penicillinase-producing strains of Neisseria gonorrhoeae in Zambia, the efficacies of single intramuscular doses of aqueous procaine penicillin G (4.8 x 10(6) units plus 1 g of oral probenecid) and 2 g of spectinomycin were evaluated in an open clinical trial of the treatment of acute gonococcal urethritis in men. The former regimen was given to 123 men; failure of treatment was observed in 9.1% of the 88 men followed for two weeks. Spectinomycin was given to 124 men; treatment failure occurred in 3.8% of the 104 men followed for two weeks. During the trial, 190 unselected isolates of N. gonorrhoeae were screened by rapid iodometric test, and two penicillinase-producing strains were detected. MICs of penicillin and spectinomycin were determined by the agar dilution method for 110 and 98 isolates, respectively. MICs of penicillin of greater than or equal to 0.125 micrograms/ml were observed with 78.2% of the strains, while 83.7% had MICs of spectinomycin of less than or equal to 15.0 micrograms/ml. It was suggested that penicillin be given routinely for treatment of gonorrhea in Zambia and that spectinomycin be reserved for treatment of gonococcal infections not cured by penicillin.

Acute Disease↗
PubMedDate not supplied

The neuromuscular blocking action of spectinomycin on the mouse hemidiaphragm preparation.

1. The mechanism of action of the muscle paralysing property of the antibiotic spectinomycin has been investigated on the isolated mouse phrenic nerve-hemidiaphragm preparation. 2. Spectinomycin produced a neuromuscular blockade that was poorly reversed by neostigmine (3 mumol/l) but well reversed by both calcium (5 mmol/l) and 3,4-diaminopyridine (0.1 mmol/l). 3. Intracellular techniques were used to record endplate potentials and miniature endplate potentials from hemidiaphragms paralysed by spectinomycin. Miniature endplate potentials were reduced both in frequency and in amplitude. The quantal content of the endplate potential during spectinomycin paralysis calculated by the method of variance was 14, a value similar to that found in preparations paralysed by the prejunctionally active magnesium. 4. Thus spectinomycin possesses weak neuromuscular blocking activity by a predominant action on acetylcholine release.

Action Potentials↗
PubMed1976

Sucrose-dependent spectinomycin-resistant mutants of Escherichia coli.

Spectinomycin-resistant (Spcr) mutants of Escherichia coli were isolated from nutrient agar plates containing 20% sucrose and 100 mug of spectinomycin per ml. About one-third of the Spcr mutants thus obtained were sucrose dependent (Sucd) and were classified into two types: I, those unable to grow on sucrose-free medium in the presence of spectinomycin; and II, those unable to grow on sucrose-free medium irrespective of the presence of spectinomycin. Most of these mutants were hypersensitive to antibiotics, dyes, and detergents and were abnormal in cell morphology, suggesting changes in cell envelopes. Reversion experiments indicated that the sucrose-dependent spectinomycin resistance and hypersensitivity to various chemicals were not independently induced properties. The Sucd-Spcr mutations of type I mutants were transducible by phage P1 and were mapped at the strA-aroE region.

Acriflavine↗
PubMed1977

Interaction of cytoplasmic membrane and ribosomes in Escherichia coli: spectinomycin-induced disappearance of membrane protein I-19.

Incubation of Escherichia coli with spectinomycin caused the disappearance of a major protein from the cytoplasmic membrane. This protein, called "I-19", was not a ribosomal protein. Its disappearance was not a result of the direct action of spectinomycin on the cytoplasmic membrane, but a result of its action on ribosomes. The disappearance was specifically induced by spectinomycin, and other antibiotics such as neomycin, erythromycin, and chloramphenicol had no effect. Although growth was not required for spectinomycin-induced disappearance of protein I-19 from the cytoplasmic membrane, the disappearance was not observed under conditions where protein synthesis was inhibited completely either by the addition of chloramphenicol or by cooling in ice. It is suggested that at least some ribosomes interact with the cytoplasmic membrane and that a modification of the mode of interaction through the action of spectinomycin on ribosomes caused the deletion of membrane protein I-19.

Bacterial Proteins↗
PubMed1984

Spectinomycin as initial treatment for gonorrhoea.

The prevalence of penicillinase producing Neisseria gonorrhoeae at this hospital increased exponentially from less than 0.5% in 1978 to 6.5% of all isolates in 1982. In January 1983 first line treatment for uncomplicated heterosexual anogenital gonorrhoea was therefore changed from ampicillin and probenecid to spectinomycin. This subsequently cured 95% of cases seen at the Praed Street Clinic. Although there was an initial fall in the monthly isolation rate of penicillinase producing N gonorrhoeae after the introduction of spectinomycin, this was not maintained. The exponential increase in the prevalence of the strain did slow in 1983, rising to only 8.7%. This, however, may have reflected a general decline in the rate of increase of penicillinase producing N gonorrhoeae throughout Britain. The failure to influence the prevalence of penicillinase producing N gonorrhoeae to any great degree may have been due in part to spectinomycin resistance in both penicillinase producing and non-penicillinase-producing N gonorrhoeae. All of the isolates appeared identical, apart from the presence of the 4.4 megadalton plasmid in penicillinase producing N gonorrhoeae, but they could not be linked epidemiologically. Changing treatment in only one of the many venereal diseases clinics in London, where patients have open access to all such clinics, is unlikely to affect the prevalence of penicillinase producing N gonorrhoeae. This has probably been more important than spectinomycin resistance in limiting the effectiveness of spectinomycin in reducing the prevalence of the strain.

Adolescent↗
PubMed1987

Plasmid profile of Neisseria gonorrhoeae in Nigeria and efficacy of spectinomycin in treating gonorrhoea.

The prevalence of penicillinase producing Neisseria gonorrhoeae (PPNG) strains has been steadily rising in Nigeria since 1979, and now about 80% of the strains of gonococci isolated in Ibadan are found to produce penicillinase. Spectinomycin has consequently become widely used in treating these infections. To ascertain the emergence of spectinomycin resistance, this study was undertaken to assess the in vivo susceptibilities of gonococcal strains to spectinomycin and other common antibiotics. Five hundred and twenty seven isolates were tested, of which 452 (85.5%) were PPNG strains. None of the strains were found to be resistant to 100 micrograms spectinomycin discs in vitro, whereas all 370 patients treated with the antibiotic were bacteriologically cured. Plasmid analysis shows that both "Asian" and "African" PPNG types are circulating in Nigeria. For the moment spectinomycin remains highly effective in treating gonococcal infections in west Africa.

Drug Resistance, Microbial↗