Spectinomycin chemistry. III.9-EPI-4(R)-dihydrospectinomycin and 9-epi-spectinomycin.
Explore the source record for details and available documents.
Bacteria↗
SEARCH · PubMed Health
Results for “Spectinomycin”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
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↗
[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↗
[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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Drugs five years later. Spectinomycin.
A single intramuscular injection of 0.2 g of spectinomycin hydrochloride is highly effective for the treatment of uncomplicated anogenital infections with Neisseria gonorrhoeae. Spectinomycin hydrochloride is indicated for uncomplicated anogenital gonococcal infections in men and women who cannot receive penicillin or probenecid, and is the drug of choice for the retreatment of patients with uncomplicated anogenital gonococcal infection who have not responded to other antibiotics. A single dose of spectinomycin does not appear to be reliably effective in the treatment of gonococcal pharyngitis. Preliminary reports indicate that multiple-dose schedules of spectinomycin will prove to be effective in gonococcal pelvic inflammatory disease and disseminated gonococcal infection. In the dosage used for gonococcal infections, spectinomycin has little effect on infection with Treponema pallidum. Evaluation of this antibiotic against other microorganisms suggests little utility for this agent in conditions other than gonococcal infections.
Animals↗
Spectinomycin - experimental investigations on possible side-effects.
Experimental investigations were performed to elaborate the immunogenic and anaphylactoid properties of spectinomycin. In guinea-pigs, no allergy against spectinomycin could be elicited. Furthermore, the absence of immunologic cross-reactions between spectinomycin and penicillin could be confirmed. The anaphylactoid activity of spectinomycin was found to be of very low order. No mast cell degranulating action could be observed. The data collected in this study permit the statement that - as far as acute unwanted actions of antibiotics are concerned - spectinomycin is an extremely safe drug.
Anaphylaxis↗
Activity of spectinomycin against anaerobes.
The in vitro inhibitory activity of spectinomycin was tested against various anaerobic bacteria. Different results were obtained with different media and with different initial pH's of the media. The highest minimum inhibitory concentrations for Bacteroides fragilis ([Formula: see text] 128 mug/ml) were obtained with the use of Wilkins-Chalgren agar (pH 7.2) and Brucella blood agar (pH 7.0). Brucella blood agar at higher pH's (7.4 and 8.0) and Mueller-Hinton and Diagnostic Sensitivity Test agars produced lower minimum inhibitory concentrations (32 and 64 mug/ml). This same relationship between spectinomycin activity and pH of the medium was, in general, observed with these media and other anaerobes, including isolates of B. melaninogenicus, Fusobacterium, gram-positive cocci, Clostridium perfringens, and C. ramosum. The variable results observed in this study and in two others make it difficult to predict the clinical usefulness of spectinomycin in the treatment of anaerobic infections. It is probably most appropriate to be guided by results obtained with Wilkins-Chalgren agar and the method proposed as a reference to the National Committee for Clinical Laboratory Standards. These results indicate that spectinomycin is not a potent inhibitor of B. fragilis or other clinically significant anaerobes.
Anaerobiosis↗
Effect of spectinomycin on T. pallidum in incubating experimental syphilis.
Animal experiments were performed to determine if a single-dose treatment for acute gonorrhoea with 2 g. spectinomycin could cure a simultaneously acquired syphilis at a very early stage of incubation. 300 treponemes (Nichols stain T. pallidum) were inoculated intratesticularly and 3 days later spectinomycin was administered in a dose which produced spectinomycin serum levels similar to those in patients who had received a single oral dose of 2 g. This dosage of spectinomycin did not prevent the development of syphilitic orchitis or reactivity to the FTA-ABS test, but it prolonged the subclinical incubation period.
Animals↗
Spectinomycin-resistant Neisseria gonorrhoeae.
Neisseria gonorrhoeae resistant to high levels of spectinomycin (more than 2,048 microng/ml), were isolated from specimens obtained from a patient with urethritis. The bacterial resistance to spectinomycin is probably due to ribosomal changes that are a result of a chromosomal mutation. If spectinomycin fails to cure gonorrhea, spectinomycin resistance should be considered.
Adult↗
Interaction of the cytoplasmic membrane and ribosomes in Escherichia coli; altered ribosomal proteins in sucrose-dependent spectinomycin-resistant mutants.
Alterations in the ribosomes of sucrose-dependent spectinomycin-resistant (Sucd-Spcr) mutants of Escherichia coli were studied. Subunit exchange experiments showed that 30S subunits were responsible for the resistance of ribosomes to spectinomycin in all Sucd-Spcr mutants tested. Proteins of 30S ribosomes were analyzed by carboxymethyl cellulose column chromatography based on their elution positions. Mutants YM22 and YM93 had an altered 30S ribosomal protein component, S5, and mutant YM50 had an altered protein, S4. Although a shift of elution position was not detected for all the 30S ribosomal proteins from mutant YM101, the amount of protein S3 was appreciably lowered in the isolated 30S subunits. A partial reconstitution experiment with protein S3 prepared from both the wild-type strain and YM101 revealed that the mutant had altered protein S3 which is responsible for the spectinomycin resistance. These alterations in 30S subunits are discussed in relation to the interaction between ribosomes and the cytoplasmic membrane.
Cell Membrane↗