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[Results of the treatment of acute gonorrhea with spectinomycin. Comparison with the combination of aqueous penicillin and probenecid].

Results following treatment of acute gonorrhea with aqueous penicillin combined with probenecid and spectinomycin hydrochloride (2.0 g) are compared and found to be statistically equivalent. Therefore, if a patient is allergic to penicillin, spectinomycin hydrochloride can be regarded as a valuable alternative. The results appear to be the same whether probenecid is administered simultaneously or 1/2-2 h before penicillin. It is advisable to control all patients one week after therapy. A second control after 2 weeks for men and after the next menstruation for women is highly desirable. If the patient fails to respond to treatment, not only an increase in the antibiotic dose, but also prolongation of therapy by administering the same dose on 3 consecutive days, is effective.

Drug Therapy, Combination↗

Prevention of swine dysentery with a combination of lincomycin and spectinomycin and resistance of swine dysentery to tylosin and sodium arsanilate.

The addition of a combination of lincomycin and spectinomycin to feed at the total concentrations of 44 and 77 mg/kg, beginning at the time of exposure and continuing for 8 weeks, prevented experimentally induced swine dysentery in swine. The disease did not develop after the medication was withdrawn. In contrast, swine dysentery, similar to that seen in the nonmedicated swine, did develop in simultaneously exposed swine treated with feed containing either 44 mg of tylosin or 99 mg sodium arsanilate/kg. The swine fed sodium arsanilate and which developed hemorrhagic diarrhea had a more severe form of this type of diarrhea than did the nonmedicated swine. After reexposure to inefective inoculum of swine dysentery 86 days after initial exposure, all remaining swine previously medicated with either tylosin or sodium arsanilate and all nonmedicated swine were immune; whereas 17 of the 24 swine fed the combination of lincomycin and spectinomycin were susceptible to swine dysentery and developed diarrhea.

Aniline Compounds↗

The treatment of gonococcal proctitis. An evaluation of 173 patients treated with 4 g of spectinomycin.

A group of 1,533 homosexual males were examined in 1976 for gonorrhea at the Skin Clinic of the Boston Dispensary. This examination included a rectal culture. There were 213 males with positive rectal cultures: an infection rate of 13.7%. Of these, 173 were treated with 4 g of spectinomycin hydrochloride, intramuscularly, and 127 (73.4%) returned in one week for a posttreatment examination and culture. All who returned had a negative culture. Four grams of intramuscular spectinomycin hydrochloride appears to be effective in the treatment of gonococcal proctitis.

Adolescent↗

Studies directed toward the total synthesis of antibiotics: (+)-spectinomycin.

The presence of a dioxaspiro or a fused bicyclic ring system resulting from a diastereoselective intramolecular acetalization of keto diol or keto alcohol units respectively, is a unique structural feature among a number of biologically important natural products. The particular bond arrangement around the ketal carbon atom is, in part, a reflection of the preference for anomeric stereoselection in nature, either at the site of acetalization or in its vicinity. This phenomenon manifests itself in the constitutional structures of several ionophores (polyether type), in the antibiotic spectinomycin as well as other natural products. Synthetic efforts in this area will be discussed, with particular emphasis on spectinomycin as a challenging target.

Carbohydrates↗

New microbiological method for determining spectinomycin in pelleted and meal feeds using trifluoroacetic acid as primary extractant.

A new microbiological method, identified as the spectinomycin trifluoroacetic (SPE-TFA) method, was compared with the current AOAC method for analyzing spectinomycin in meal and pelleted feeds fortified with LS-20 premix. Feeds containing 3 concentrations of drugs and a zero level were tested in a correlation study. The data showed no significant differences in the percent of theory assayed between meal and pelleted samples using the SPE-TFA method, but the percent of theory found using the AOAC method was significantly lower for the pelleted samples than for the meal samples. The within-sample variation of the AOAC assay was also not the same for all samples; the SPE-TFA assay variation was relatively constant for all samples. The SPE-TFA method produced an overall average recovery of 98% with a range of 89-109% compared with an 85% recovery ranging from 64 to 102% for the AOAC method. In addition to producing better recoveries, the SPE-TFA method features a more sensitive response line, and final test solutions have viscosities and clarity more comparable to the standard solutions than those produced by the current AOAC method.

Animal Feed↗

Penicillin-sensitive spectinomycin-resistant Neisseria gonorrhoeae.

The first identification in Australia of a penicillin-sensitive spectinomycin-resistant Neisseria gonorrhoeae organism is reported. The method of identification is detailed. Caution is recommended in the use of spectinomycin for the primary treatment of gonorrhoea.

Adult↗

[Spectinomycin sensitivity of Neisseria gonorrhoeae].

Using the agar dilution technique minimal inhibitory concentrations (MIC) with respect to spectinomycin were determined. 92 Neisseria gonorrhoeae isolates collected in a STD outpatient clinic and 160 Neisseria gonorrhoeae isolates collected from prostitutes were investigated. One isolate imported from Asia had a MIC of greater than 1024 micrograms/ml and was resistant. All other isolates, three penicillinase producing strains included, had MICs of 4-32 micrograms/ml and were sensitive to spectinomycin.

Drug Resistance, Microbial↗

Comparative study of ceftriaxone and spectinomycin for treatment of pharyngeal and anorectal gonorrhea.

Of the currently recommended regimens for treatment of uncomplicated gonorrhea, only aqueous penicillin G procaine is effective against infections at all sites. However, procaine penicillin is not effective against penicillinase-producing Neisseria gonorrhoeae and suffers from poor patient acceptability owing to the 10-mL volume of injection and allergic and toxic procaine reactions. Ceftriaxone is a new extended-spectrum cephalosporin with a long serum half-life and is many times more active than penicillin G against both beta-lactamase-positive or -negative strains of N gonorrhoeae. Ceftriaxone was compared as a single, 125-mg, 0.5-mL injection with a single 2-g injection of spectinomycin in difficult to treat pharyngeal gonorrhea in men and women and anorectal gonorrhea of men. Ceftriaxone cured 30/32 (94%) pharyngeal and 52/52 anorectal infections, compared with 6/14 (43%) and 9/9, respectively, for spectinomycin. Both regimens were well tolerated. Ceftriaxone may prove to be a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and/or penicillinase-producing N gonorrhoeae is prevalent.

Adult↗

Single-dose treatment of gonococcal urethritis in males: evaluation of procaine penicillin, ampicillin and spectinomycin.

Males with acute gonococcal urethritis were treated at random with 2.4 million units aqueous procaine penicillin G intramuscularly plus 1.0 g. probenecid orally, 3.5 g. ampicillin orally plus 1.0 g. probenecid orally, or 2.0 g. spectinomycin intramuscularly. The overall follow-up was 97%. All treatments were of equal efficacy, eradication of gonococcal disease being observed in 93 to 97% of treated patients. Treatment failures occurred in each drug group and pre-treatment isolates recovered from these cases showed decreased susceptibility to the agent used. Aqueous procaine penicillin G plus probenecid remains the preferred therapy for gonorrhea. For patients hypersensitive to penicillin, spectinomycin is currently a reasonable alternative drug. This agent, unlike procaine penicillin-probenecid, is probably ineffective against concurrent incubating syphilis, and future development of bacterial resistance is a definite possibility.

Administration, Oral↗

[Sensitivity of Neisseria gonorrhoeae to spectinomycin].

The susceptibility of 408 strains of N. gonorrhoeae to spectinomycin was determined by an agar plate dilution test. The 401 beta-lactamase-negative and 7 beta-lactamase-positive strains were isolated from patients of the Department of Dermatology, University of Munich, in the years 1977 to 1980. The minimum inhibitory concentrations (MIC) ranged from 2 to 32 micrograms/ml. Only one strain was less susceptible with a MIC of 64 micrograms/ml. A comparison between the isolates of 1977/1978 and 1979/1980 showed no decrease in the susceptibility to spectinomycin.

Microbial Sensitivity Tests↗

Mutations to spectinomycin resistance which alleviate the restriction of an amber suppressor by streptomycin resistance.

Unlike mutations to streptomycin resistance, which restrict the function of an SU II amber suppressor, mutations to spectinomycin resistance have no restrictive effect. Furthermore, mutations to spectinomycin resistance counteract the restrictive action of streptomycin-resistant mutations when combined in a single strain. The mutations to drug resistance, singly or in combination, do not themselves lead to any detectable suppressor activity. The effects on SU II are interpreted in terms of interactions between ribosomal elements.

Coliphages↗

Ribosomal RNA and protein mutants resistant to spectinomycin.

We have compared the influence of spectinomycin (Spc) on individual partial reactions during the elongation phase of translation in vitro by wild-type and mutant ribosomes. The data show that the antibiotic specifically inhibits the elongation factor G (EF-G) cycle supported by wild-type ribosomes. In addition, we have reproduced the in vivo Spc resistant phenotype of relevant ribosome mutants in our in vitro translation system. In particular, three mutants with alterations at position 1192 in 16S rRNA as well as an rpsE mutant with an alteration of protein S5 were analysed. All of these ribosomal mutants confer a degree of Spc resistance for the EF-G cycle in vitro that is correlated with the degree of growth rate resistance to the antibiotic in culture.

Escherichia coli↗

Organization and nucleotide sequence of ten ribosomal protein genes from the region equivalent to the spectinomycin operon in the archaebacterium Halobacterium marismortui.

The nucleotide sequence has been determined of a 4700 bp region from a ribosomal protein gene cluster of Halobacterium marismortui (Haloarcula marismortui), which is equivalent to part of the spectinomycin operon of Escherichia coli. The genes were localized on the recombinant lambda EMBL3 clone PP*7, which also contains several other ribosomal protein genes from the DNA region in H. marismortui equivalent to the linked S10/spc operon. The genes analysed encode ten ribosomal proteins, namely HmaL5, HmaS14, HmaS8, HmaL6, HL5, HL24, HmaL18, HmaS5, HmaL30 and HmaL15. The gene organization of the archaebacterial cluster is similar to that in eubacteria but has two additional genes, namely those encoding HL5 and HL24, which were identified as extra proteins that are apparently not present in E. coli. These correspond to the gene products of orfd and orfe in Methanococcus vannielii and also have eukaryotic counterparts.

Amino Acid Sequence↗

Spectinomycin operon of Micrococcus luteus: evolutionary implications of organization and novel codon usage.

The complete DNA sequence of the Micrococcus luteus spectinomycin (spc) operon and its adjacent regions has been determined. The sequence has revealed the presence of genes that are homologous to those of the Escherichia coli ribosomal and related proteins, L14, L24, L5, S8, L6, L18, S5, L30, L15, and secretion protein Y (sec Y), and the gene for adenylate kinase (adk). The gene arrangement in the spc operon is essentially the same as that of E. coli except for the absence in the M. luteus spc operon of the genes for S14 and X protein that exist in the E. coli spc operon. SecY and adk seem to be composed of another operon (adk operon) with at least an open reading frame. The deduced amino acid sequences for these ribosomal proteins are well conserved among the two species (40-65% identity). Reflecting the high genomic guanine and cytosine (GC) content of M. luteus (74%), the codon usage of the genes is extremely biased toward use of G and C, about 94% of the codon third positions being G or C. Seven codons, AUA, AAA, AGA, UUA, GUA, CUA, and CAA, all of which have A at the codon third positions, are completely absent in the M. luteus genes examined. Out of 11 genes in the M. luteus spc and adk operons, 5 (10) use GUG (UGA) and 6 (1) use AUG (UAA) as an initiation (termination) codon.

Amino Acid Sequence↗

Nucleotide sequence of four genes encoding ribosomal proteins from the 'S10 and spectinomycin' operon equivalent region in the archaebacterium Halobacterium marismortui.

Four genes encoding ribosomal proteins HmaS17, HmaL14, HmaL24 and HS3, have been identified in the lambda EMBL3 clone PP*7 from a genomic library of the archaebacterium Halobacterium marismortui. The clone contains genes from the 'S10 and spectinomycin' operon equivalent region. Three of the deduced proteins are homologous to the corresponding Escherichia coli and Methancoccus vannielii S17, L14 and L24 proteins, as well as to eukaryotic proteins from rat or yeast. HS3 was identified as an extra protein corresponding to the gene product for orfc in M. vannielii and the eukaryotic ribosomal protein RS4 from rat. The equivalence of HmaL24 (HL16) and E. coli L24, which share only 28% identical amino acid residues, could now be shown by localizing the HmaL24 gene at the same position in the cluster.

Amino Acid Sequence↗

Organization and structure of the Methanococcus transcriptional unit homologous to the Escherichia coli "spectinomycin operon". Implications for the evolutionary relationship of 70 S and 80 S ribosomes.

By means of an immunological approach and a subsequent chromosome-walking strategy a chromosomal region encoding ribosomal proteins in the archaebacterium Methanococcus vannielii was cloned. The determination of the nucleotide sequence of the 7.8 x 10(3) base DNA fragment revealed the existence of 14 putative ribosomal protein genes and two unidentified open reading frames. They are organized in a transcriptional unit that is very similar to the Escherichia coli "spectinomycin operon" in respect of both gene composition and gene order. The Methanococcus transcriptional unit contains, in addition to those genes whose products have a homologue in the E. coli operon, three genes whose products share sequence similarity with eukaryotic 80 S but not with eubacterial ribosomal proteins. The Methanococcus ribosomal proteins almost exclusively exhibit a higher sequence similarity to eukaryotic 80 S ribosomal proteins than to those of eubacteria and many of them have a size intermediate between those of their eukaryotic and eubacterial homologues. These results are discussed in terms of a hypothesis that implies that the recent eubacterial ribosome developed by a "minimization" process from a more complex organelle and that the archaebacterial ribosome has maintained features of this ancestor.

Archaea↗

The aminoglycoside-resistance operon of the plasmid pSa: nucleotide sequence of the streptomycin-spectinomycin resistance gene.

The nucleotide sequence of the probable C terminus of the kanamycin-resistance gene (KmR) and the probable complete sequence of the streptomycin-spectinomycin-resistance gene (SpR) of the IncW plasmid pSa have been determined. The two genes appear to be oriented in the same direction and separated by a spacer region of 53 bp, with transcription proceeding from the KmR gene into the SpR gene. An RNA transcript encompassing the C terminus of the KmR gene, the 53-base spacer, and the N terminus of the SpR gene has the potential to form a stem-loop structure with a free energy value of -68 kcal/mol. The SpR gene of pSa has extensive sequence homology with the aadA gene of the plasmid R538-1. Comparison of the proposed amino acid sequence of the KmR protein of pSa with those of two aminoglycoside phosphotransferases revealed a region of potential homology with those proteins.

Base Sequence↗

Construction of a Tn5 derivative determining resistance to gentamicin and spectinomycin using a fragment cloned from R1033.

A physical and genetic map of the IncP plasmid R1033 was constructed: restriction fragments were subcloned and antibiotic resistance genes were located. The map is consistent with previous reports that R1033 is a derivative of RP4 carrying a 16-kb transposon Tn1696 which contains the antibiotic-resistance determinants present on R1033 but not on RP4. A BamHI fragment from R1033, determining resistance to gentamicin, spectinomycin and streptomycin, was cloned into Tn5, replacing the central Bg/II fragment that determined kanamycin resistance, producing a recombinant transposon Tn5-GmSpSm. This was shown to transpose in Rhizobium leguminosarum at a frequency similar to that of the parental Tn5.

DNA Transposable Elements↗