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PubMed1974

Selective inhibition of initiating ribosomes by spectinomycin.

Spectinomycin at low concentrations inhibits initiating ribosomes but not ribosomes already engaged in chain elongation. The initiating ribosomes are blocked in some step after formation of the initiation complex, probably the first translocation. Cells inhibited by spectinomycin accumulate polysomes, and these have proved to be unstable polyinitiation complexes: they can be pulse-labeled with methionine but not with valine, and they disappear after addition of rifampicin. Hence, the blocked ribosomes evidently are released and then reinitiate. In heterozygotes this cyclic reinitiation by the sensitive ribosomes, each blocking an initiation site for an average of 10-15 min, can explain (just as with streptomycin) the dominance of sensitivity over resistance.

Bacterial Proteins↗
PubMed2005

Detection of a novel aph(2") allele (aph[2"]-Ie) conferring high-level gentamicin resistance and a spectinomycin resistance gene ant(9)-Ia (aad 9) in clinical isolates of enterococci.

Aminoglycoside-modifying enzymes (AMEs) are major factors that confer aminoglycoside resistance to enterococci. In an epidemiologic study on distribution of 12 AME genes in 534 recent clinical strains isolated from a Japanese hospital, two uncommon AME genes, ant(9)-Ia and a novel aph(2") allele, aph(2")-Ie, were detected. ant(9)-Ia had been reported only in Staphylococcus aureus and encodes spectinomycin adenylyltransferase ANT(9)-I, which confers resistance to spectinomycin. The ant(9)-Ia gene was detected in three strains, a single strain each of Enterococcus faecalis, E. faecium, and E. avium. Nucleotide sequences of ant(9)-Ia from these three enterococcal species were identical to that reported for S. aureus and considered to be located on Tn 554. The new aph(2") allele, designated aph(2")-Ie, was identified in three E. faecium strains. The aph(2")-Ie allele was genetically close to aph(2")-Id reported in E. casseliflavus (93.7% amino acid sequence identity; 96.3% similarity), while distant from aph(2")-Ia, aph(2")-Ib, or aph(2")-Ic (26.3-29.5% amino acid sequence identity). Sequence divergence between APH(2")-Id and APH(2")-Ie was mostly located in amino-terminal half. In contrast, sequences corresponding to the three motifs required for aminoglycoside phosphotransferase were conserved except for a single amino acid. Three E. faecium strains having aph(2")-Ie showed high-level resistance to gentamicin and streptomycin, but not to kanamycin, dibekacin, and tobramycin, unlike enzyme specificity described for aph(2")-Id in E. casseliflavus. Such a difference in resistance phenotype was suggested to be related to amino acid sequence divergence between APH(2")-Id and APH(2")-Ie.

Alleles↗
PubMed1995

A new mutation in 16S rRNA of Escherichia coli conferring spectinomycin resistance.

We report a novel mutation, C1066U in 16S rRNA which was selected for resistance to spectinomycin, an antibiotic which inhibits ribosomal translocation. The minimal inhibitory concentration (MIC) of spectinomycin determined for this mutant (15 micrograms/ml) is greater than with the wild-type plasmid (5 micrograms/ml) but lower than with the well known C1192U mutation (> 80 micrograms/ml). The C1066U mutation also increases the cells sensitivity to fusidic acid, another antibiotic which inhibits translation at the translocation stage, whereas C1192U is unchanged relative to the wild type. We discuss why the acquisition of resistance to one of these drugs is often associated with hypersensitivity to the other.

Base Sequence↗
PubMed2002

In vivo selection of spectinomycin-binding RNAs.

The folding of even short RNA molecules in a random library can produce a huge number of possible macromolecular structures. Using this principle, we have designed selections to seek non-coding RNA transcripts capable of interfering with specific macromolecules such as transcription factors in living bacterial cells. Here we show that such selections can uncover an unexpected class of RNAs. In the present case, we report short RNA transcripts whose expression confers bacterial resistance to the antibiotic spectinomycin. We provide evidence that such RNAs cause drug resistance by direct antibiotic binding, demonstrating a class of spectinomycin-specific functional molecular decoys built from RNA.

Anti-Bacterial Agents↗
PubMedDate not supplied

A trial of spectinomycin hydrochloride compared with aqueous penicillin G plus kanamycin for treatment of severe pelvic inflammatory disease.

In a randomized, double-blind, comparative study, eight patients with severe pelvic inflammatory disease received intravenous spectinomycin hydrochloride (8 g per day), and nine received aqueous penicillin G (2.0 x 10(7) units per day, iv) plus kanamycin (1 g per day, im). Three patients assigned to spectinomycin had to have the therapy discontinued, two because of therapeutic failures and one because of an adverse reaction. None of the patients assigned to penicillin plus kanamycin needed cessation of treatment. Even though the differences were not statistically significant, the study was thus terminated.

Adult↗
PubMedDate not supplied

Association of auxotypes of Neisseria gonorrhoeae and susceptibility to penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam.

Isolates of Neisseria gonorrhoeae from 304 patients attending a venereal disease clinic were examined by a plate dilution method for their susceptibility to six antibiotics: penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam. The isolates were also characterized by gonococcal auxotyping. The most frequent auxotypes were Nonrequiring, 58%; Pro-, 14%; Pro- Arg (Orn*) Ura-, 14%; Arg- Hyx- Ura-, 6%; and a miscellaneous group consisting of 8% of the isolates. If the entire group of isolates were examined, moxalactam was the most active of the antibiotics; 94% of the isolates were inhibited by less than or equal to 0.25 microgram/ml. The Pro- Arg (Orn*) Ura- isolates were relatively resistant to penicillin G and cefoxitin. The Arg- Hyx- Ura- group of isolates was the most susceptible of the auxotypes to all of the antibiotics except spectinomycin. The uncommon auxotype Arg (Orn*) Ura- has a requirement for arginine that is satisfied by citrulline but not by ornithine. The results of the present study indicate that the nutritional requirements of gonococci may be associated with their response to certain antibiotics.

Amino Acids↗
PubMedDate not supplied

Thiamphenicol in the treatment of gonococcal infections: a comparative trial with penicillin and spectinomycin.

The efficacy of thiamphenicol for treatment of uncomplicated gonococcal infection was compared with that of penicillin and spectinomycin in 370 women confined in the clinic to preclude reinfection before evaluation of treatment. Thiamphenicol (2.5 g perorally) was highly effective against beta-lactamase-producing Neisseria gonorrhoeae, but the failure rate in infections with non-beta-lactamase-producing N. gonorrhoeae was high. This rate was not, however, significantly higher than that for beta-lactamase-producing strains. The failure rate with thiamphenicol was significantly higher than that with spectinomycin (2 g im) in the treatment of infections due to beta-lactamase-producing N. gonorrhoeae but was essentially similar to that observed with aqueous procaine penicillin G (4.8 X 10(6) units im) plus probenecid (1 g perorally) among non-beta-lactamase-producing N. gonorrhoeae. Therefore thiamphenicol may be used as an alternative therapy for gonorrhea, especially for infections due to beta-lactamase-producing strains.

Adolescent↗
PubMedDate not supplied

Comparison of thiamphenicol and spectinomycin in the treatment of uncomplicated gonorrhea in men.

Thiamphenicol (2.5 g perorally) was compared with spectinomycin (2.0 g im) in the treatment of uncomplicated gonococcal urethritis in men. Patients were selected on the basis of cultures positive for Neisseria gonorrhoeae and were randomly assigned to one of the treatment regimens. Test-of-cure cultures were done three to five days after treatment. Beta-lactamase activity of every isolate was tested. In the group treated with thiamphenicol, 152 patients were followed; 63 (41.4%) failed to be cured, while the spectinomycin regimen gave a cure rate of greater than 95%. Penicillinase-producing strains gave a greater rate of failure than non-penicillinase-producing strains. The strains of N. gonorrhoeae isolated in Seoul had high minimal inhibitory concentrations of various antibiotics. About 48% of strains had a MIC of greater than or equal to 2 micrograms of thiamphenicol/ml. Hematologic examinations, repeated on days 0, 3-5, 10, and 30 of treatment, revealed no appreciable toxicity following the thiamphenicol regimen.

Adolescent↗
PubMedDate not supplied

An unusual case of penicillinase-producing Neisseria gonorrhoeae resistant to spectinomycin in California.

We report a case of gonorrhea due to a penicillinase-producing strain of Neisseria gonorrhoeae resistant to spectinomycin in a 26-year-old man who had not been out of the United States for a year-and-a-half. His sexual contact also had no recent travel out of the United States. The genital and oropharyngeal infections were successfully treated with cefoxitin (1 g im) plus probenecid (1 g orally) and trimethoprim-sulfamethoxazole (80 mg of trimethoprim and 400 mg of sulfamethoxazole). The patient took nine of the latter tablets daily for five days. The organism was a serovar IB-3, proline-requiring auxotype. The patient's isolate contained both 2.6-megadalton and 4.4-megadalton plasmids. Measurement of minimal inhibitory concentrations (MICs) of antibiotics for the isolate confirmed the penicillin resistance and showed an MIC of spectinomycin of greater than 256 micrograms/ml. The epidemiologic investigation suggested that the source of the infection was a male contact with unusual clinical features, including bloody urethral discharge and a possible incubation period of 28 days.

Adult↗
PubMedDate not supplied

Single-dose treatment of uncomplicated acute gonococcal urethritis in Ethiopian men: comparison of rosoxacin, spectinomycin, penicillin, and ampicillin.

A total of 140 Ethiopian men with gonococcal urethritis were randomly assigned to treatment with aqueous procaine penicillin G (4.8 X 10(6) units intramuscularly [im] plus 1.0 g of oral probenicid); oral ampicillin (3.5 g plus 1.0 g of oral probenicid); spectinomycin (2.0 g im); or oral rosoxacin (Acrosoxacin; 300 mg). Failure rates were 24%, 19%, zero, and 3%, respectively. Forty-four (31.4%) patients were infected with penicillinase-producing Neisseria gonorrhoeae (PPNG) and were evenly distributed in the treatment groups. All 39 PPNG strains analyzed for plasmid content possessed a 2.6-Mdalton plasmid; 28 (71.8%) had a 3.2-Mdalton beta-lactamase-encoding plasmid, ten (25.6%) had a 4.4-Mdalton plasmid (three with and seven without a 24.5-Mdalton plasmid), and one had only a 24.5-Mdalton plasmid. Two patients were infected with N. gonorrhoeae-possessing plasmids apparently capable of encoding but not producing beta-lactamase. Both spectinomycin and rosoxacin are excellent single-dose treatment regimens for gonococcal urethritis in men. All people receiving these drugs in Ethiopia should be tested serologically for syphilis, however, as eight (11.8%) of 68 men in this study also had active latent syphilis.

4-Quinolones↗
PubMed1983

Systemic anaphylaxis caused by parenteral spectinomycin.

Spectinomycin is commonly used for the treatment of uncomplicated gonorrhea, and is considered to be a safe drug. We have described a case of anaphylaxis characterized by peripheral vascular collapse after intramuscular administration of spectinomycin.

Adult↗
PubMed1972

Bactericidal action of streptomycin and comparison with spectinomycin in heterozygotes of Escherichia coli.

Str(s)/str(r) heterozygotes of Escherichia coli K-12 are shown to be sensitive to the lethal as well as the inhibitory action of streptomycin. The rate of killing was lower in heterozygotes than in sensitive homozygotes, and among heterozygotes it was lower in those with a higher proportion of resistant ribosomes. These strains also differed, in a parallel manner, in the kinetics of inhibition of growth and protein synthesis by streptomycin. Similar results were obtained with spectinomycin and corresponding merodiploid strains. Since spectinomycin is purely bacteriostatic and stabilizes polysomes, it must block resistant ribosomes behind inhibited sensitive ribosomes; hence, these results are consistent with an initial similar polysomal blockade by streptomycin. However, since streptomycin causes gradual polysome breakdown, its dominant lethal action must involve some mechanism other than a permanent polysomal blockade.

Antibiotics, Antineoplastic↗
PubMed1978

Improved radioenzymatic assay for spectinomycin.

The sensitivity and reproducibility of the radioenzymatic adenylylating assay for spectinomycin were improved by modifications of the assay procedure and by partial purification of the enzyme. The presence of Bacillus subtilis ribosomes or S-150 fraction in the enzymatic reaction mixture interfered with the ability to measure spectinomycin by this method.

Adenosine Monophosphate↗
PubMed1972

In vitro antibacterial activity of spectinomycin.

The in vitro inhibitory and bactericidal activities of spectinomycin hydrochloride were tested against a variety of bacteria. The antibiotic was inhibitory at 31.2 mug/ml to most strains of Escherichia coli, Klebsiella, Enterobacter, and Staphylococcus epidermidis. Concentrations of antibiotic exhibiting bactericidal activity exceeded the inhibitory concentration by at least fourfold. Regression graphs were plotted for results obtained with 30-, 100-, 200-, and 300-mug spectinomycin discs; tentative interpretative standards are proposed.

Bacteria↗
PubMed1973

In vitro susceptibility of Neisseria gonorrhoeae to spectinomycin examined by a broth dilution method.

The in vitro susceptibility of 113 strains of Neisseria gonorrhoeae to spectinomycin was determined by the broth dilution method and was compared with their susceptibility to penicillin and ampicillin. All strains demonstrated a susceptibility to spectinomycin in a range between 2.5 and 20 mug/ml; 96% of these strains were susceptible in a range from 5 to 10 mug/ml. The same strains were susceptible to ampicillin at concentrations between 0.06 and 0.5 mug/ml and to penicillin between 0.02 and 1.25 units/ml. For the majority of strains, the minimal inhibitory and bactercidal concentrations were identical; however, with more than 10% of the strains, the minimal inhibitory concentration was lower than the minimal bactericidal concentration.

Ampicillin↗
PubMed1986

In vitro activities of U-63366, a spectinomycin analog; roxithromycin (RU 28965), a new macrolide antibiotic; and five quinolone derivatives against Haemophilus ducreyi.

The in vitro activities of the new spectinomycin analog U-63366, the new macrolide roxithromycin (RU 28965), and five new quinolone derivatives (pefloxacin, rosoxacin, norfloxacin, ofloxacin, and ciprofloxacin) were studied against 23 multiresistant strains of Haemophilus ducreyi (beta-lactamase producers) isolated in Paris and were compared with the activities of tetracycline, minocycline, chloramphenicol, streptomycin, kanamycin, gentamicin, spectinomycin, erythromycin, and nalidixic acid. All strains were uniformly susceptible to the seven new antibiotics tested. Ciprofloxacin had the greatest inhibitory effect in vitro (the MIC for 90% of the strains tested [MIC90] was 0.016 microgram/ml), and U-63366 was the most active aminoglycoside-aminocyclitol antibiotic (MIC90, 0.25 microgram/ml).

Anti-Bacterial Agents↗
PubMed1988

Effects of aminoglycosides and spectinomycin on the synthesis and release of lipopolysaccharide by Escherichia coli.

The effects of aminoglycosides and spectinomycin on lipopolysaccharide (LPS) synthesis and release by Escherichia coli were studied. LPS synthesis was previously reported to be regulated by the stringent control mechanism. In agreement with this, the control of LPS synthesis in amino acid-deprived relA+ cells was relaxed by spectinomycin, a proven stringent control antagonist, but not by kanamycin, an agent which is ineffective as a stringent control antagonist. The other stringent control antagonists tested (gentamicin, tobramycin, and, to a lesser extent, amikacin) unexpectedly failed to relax the control of LPS synthesis, and this was subsequently shown to be due to their inhibitory action on LPS synthesis. The release of LPS by nongrowing (amino acid-deprived and antibiotic-treated) bacteria was stimulated only under conditions in which the control of LPS synthesis was relaxed.

Amikacin↗
PubMed2005

In vitro effects of spectinomycin and ceftriaxone alone or in combination with other antibiotics against Chlamydia trachomatis.

The in vitro effects of spectinomycin and ceftriaxone, alone or in combination with erythromycin, ofloxacin, and doxycycline, against Chlamydia trachomatis were investigated by the checkerboard method and compared by Ridit (reference identical unit) analysis. A combination of spectinomycin with erythromycin or doxycycline was found to be more effective than that of ceftriaxone.

Anti-Bacterial Agents↗