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The Escherichia coli cmlA gene encodes the multidrug efflux pump Cmr/MdfA and is responsible for isopropyl-beta-D-thiogalactopyranoside exclusion and spectinomycin sensitivity.

Expression of cloned genes from isopropyl-beta-D-thiogalactopyranoside (IPTG)-regulated promoters is lowered when the Escherichia coli CmlA/Cmr/MdfA efflux pump is overexpressed, probably due to IPTG exclusion from the cytoplasm. The previously reported cmlA1 mutation confers a similar phenotype. cmlA1 contains an IS30 insertion upstream of cmr/mdfA, which creates a putative promoter. CmlA overproduction also causes spectinomycin hypersensitivity.

Alleles↗

The aadA gene of plasmid R100 confers resistance to spectinomycin and streptomycin in Myxococcus xanthus.

Plasmids with the aadA gene from plasmid R100, which confers resistance to the aminoglycosides spectinomycin and streptomycin in Escherchia coli, can be introduced into wild-type Myxococcus xanthus, strain DK1622, by electroporation. Recombinant M. xanthus strains with integrated plasmids carrying the aadA gene acquire resistance to high levels of these antibiotics. Selection for aadA in M. xanthus can be carried out independently of, or simultaneously with, selection for resistance to kanamycin. The kinds and frequencies of recombination events observed between integrative plasmids with aadA and the M. xanthus chromosome are similar to those observed after the transformation of yeast. Cleavage of integrative plasmid DNA at a site adjacent to a region of homology between the plasmid and the M. xanthus genome favors the targeted disruption of M. xanthus genes by allele replacement.

Anti-Bacterial Agents↗

Treatment of gonorrhoea in the female with fortified procaine penicillin plus probenecid and with spectinomycin.

513 cases of uncomplicated gonorrhoea in females with positive results to cultures were treated with two regimens of treatment between January 1, 1972, and February 28, 1973, at the Department for Females, Bangrak Hospital, Bangkok. The highest incidence was found in the age group 20 to 24 years (215 out of 513). The patients were divided into two groups. In the first, probenecid 1 g. was given orally 1 hour before an intramuscular injection of 4 million units fortified procaine penicillin, and in the second an intramuscular injection of 2 g. spectinomycin dihydrochloride was given. 335 cases were followed in the first group and there were no failures; 132 cases were followed in the second group and there was one failure (0.7 per cent.). The fact that gonococci were found in the rectum in 23.7 per cent. of cases (117 out of 493) indicates that rectal tests are of considerable importance and should be included in the routine investigations. There was no evidence that gonorrhoeal infection of the rectum was more resistant to treatment than infection at other sites.

Adolescent↗

Cefuroxime, thiamphenicol, spectinomycin, and penicillin G in uncomplicated infections due to penicillinase-producing strains of Neisseria gonorrhoeae.

The use of cefuroxime and thiamphenicol in uncomplicated gonococcal infection was studied in 562 women confined to a clinic to preclude reinfection before cultural confirmation of cure. Cefuroxime was as effective as spectinomycin in the treatment of infections due to penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) and was significantly more effective than 4.8 units of aqueous procaine penicillin G with probenecid among non-penicillinase-producing (non-PPNG) strains. Thiamphenicol was highly effective against PPNG, but the failure rate in infections with non-PPNG was high and appeared to be related to the minimum inhibitory concentrations of thiamphenicol. This rate was not, however, significantly higher than that for PPNG strains. Thiamphenicol might therefore be used as an alternative for infections due to PPNG strains. If, however, thiamphenicol is used widely, selection of more resistant strains and thus an increasing proportion of failures may be expected.

Adolescent↗

Effect of penicillin and spectinomycin given for urethritis and cervicitis with Neisseria gonorrhoeae: high prevalence of penicillin-resistant isolates.

Efficacy of single-dose spectinomycin (TRO: 2 g intramuscularly) was compared with that of aqueous procaine penicillin G (APPG:4.8 x 10(6) units) plus 1 g of probenecid for treatment of gonococcal urethritis and cervicitis. Cure rates of the 210 patients who received TRO and 190 patients who received APPG were 97.6% and 91.1%, respectively. MICs of antibiotics were determined using the agar dilution method. Those isolates with MICs of APPG of less than 1.0 microgram/ml had low failure rates (2.9%), while strains with increased resistance to APPG (MICs greater than or equal to 1.0 microgram/ml) had higher failure rates (24%). Treatment failures seen with TRO were not correlated to isolates with the higher MICs. Clinical results suggest TRO could be given for treatment of genital gonorrhoea in Puerto Rico due to the high prevalence of both chromosomally-mediated penicillin-resistant Neisseria gonorrhoeae (20%) and penicillinase-producing Neisseria gonorrhoeae (7.5%) strains and the high rate of failure seen with the use of APPG.

Adolescent↗

Therapeutic efficacy of water-soluble lincomycin-spectinomycin powder against porcine proliferation enteropathy in a European field study.

Controlled clinical trials to a standardised protocol were conducted into the effect of a water-soluble antibiotic on proliferative enteropathy and its causative agent (Lawsonia intracellularis) on commercial pig farms at six sites in four European countries. Clinical signs of the disease and L intracellularis-specific polymerase chain reaction (PCR)-positive pigs were detected in pens of six- to 12-week-old pigs (weighing 5 to 55 kg) immediately before each trial. Matched pens of randomised pigs were either left unmedicated (32 to 59 pigs per trial), or medicated orally with 10 mg/kg of a water-soluble combination of lincomycin and spectinomycin powder (21 and 42 mg, respectively, of antibiotic activity per litre) for either seven days (33 to 61 pigs per trial), or 14 days (33 to 61 pigs per trial), delivered via the drinking water. Investigators did not know which pens received which treatment In most of the affected pigs in each trial, diarrhoea due to L intracellularis resolved within three to seven days after the medication began, whereas most unmedicated pigs remained diarrhoeic for at least 10 days. On average the medicated pigs gained more weight than the unmedicated pigs over the 21-day trial period (P=0.01). In two trials, the absence of L intracellularis after the treatment ended was confirmed by the PCR.

Administration, Oral↗

In vitro susceptibility of anaerobic flora of the female genital tract to ampicillin compared to spectinomycin.

Pelvic inflammatory disease (PID) may be caused by anaerobic bacteria and or gonococcus and therefore the efficacy of two antibiotics, ampicillin (AMP) and spectinomycin (SPM) commonly used in this setting was examined against 370 isolates of anaerobic bacteria. At the highest therapeutically achievable serum levels, AMP (16 micrograms/ml) inhibited 83% of all anaerobes and 70% of Bacterioides fragilis, and SPM (128 micrograms/ml) inhibited 98% of all anaerobes and 95% of B. fragilis strains tested. It therefore appears that both AMP and SPM may have a place in the treatment of PID. In our study, greater percentage of anaerobes were susceptible to SPM than previously reported. We used the 'glove box' technique used for testing the susceptibility of anaerobes.

Ampicillin↗

Pharmacokinetics of spectinomycin in volunteers with renal insufficiency.

The pharmacokinetics of spectinomycin hydrochloride after 2 g intravenous doses were studied in ten volunteers with varying degrees of renal function. Mean peak serum concentration in 8 volunteers with renal insufficiency was 150.9 +/- (SD) 42.3 microgram/ml which was similar to 2 normal volunteers who had concentrations of 139 and 186 microgram/ml. Serum half-lives in the volunteers with renal insufficiency ranged from 4.7 to 29.3 h and increased as creatinine clearance decreased. Serum half-lives of the 2 normal volunteers were 1.5 and 1.7 h. Urine concentrations and percents of recovery were variable.

Adult↗

In vitro assessment of the efficacy of erythromycin in combination with oxytetracycline or spectinomycin against Pasteurella haemolytica.

The effects of combining erythromycin (Ery) with oxytetracycline (Oxy) or spectinomycin (Sp) on Pasteurella haemolytica were evaluated in vitro using the chessboard (checkerboard) technique. These combinations were selected because all are drugs widely used in bovine respiratory disease treatment, and they represent possible sequential or complementary mechanisms of action. Using the recommended breakpoints of greater than 4 micrograms/ml for Ery, 16 micrograms/ml for Oxy, and 32 micrograms/ml for Sp, of the 33 P. haemolytica isolates, 32 were resistant to Oxy, 27 to Sp, and 14 to Ery. Based on the fractional inhibitory concentration index, Ery and Oxy in combination were synergistic or additive against 32 of 33 isolates. The combination of Ery and Sp was synergistic or additive against 27 of 33 isolates. No instances of antagonism were seen. When the effects were considered within the context of therapeutically achievable serum/tissue concentrations, the effects of Ery and Oxy in combination were only marginal. Thus, against P. haemolytica isolates, Ery and Sp appeared to represent an effective antimicrobial combination, whereas Ery and Oxy were only of marginal efficacy as a combination.

Animals↗

Analysis of gene cassettes of streptomycin-spectinomycin resistance of Hungarian Salmonella enterica serotype Typhimurium strains.

By PCR using the ant(3")-Ia primer pair the aadA gene was detected in 34 streptomycin- and spectinomycin-resistant Salmonella enterica serotype Typhimurium strains. Out of them 12 belonged to DT104 and 22 to non-DT104 phage type. Using different primer combinations it was demonstrated that this gene was integron-associated in all cases: in the DT104 strains it was generally contained by a 1 kb integron while in the majority of the non-DT104 strains by a 2.05 kb (less often by a 1.9 or 1 kb) integron. In the case of integrons carrying multiple cassettes the cassette containing the aadA gene was located closer to the 3' end of the integron. The aadA genes of DT104 and non-DT104 strains were different: in the former group the aadA2 gene, while in the latter group (constituted by strains of five different phages types as well as unclassifiable and untypable strains) the aadA1 gene could be identified. The RH50/RH51 primer pair described by Collis and Hall (1992) proved to be suitable for rapid discrimination between the aadA1 and aadA2 genes on the basis that the RH51 primer bound exclusively to the aadA2 gene.

Anti-Bacterial Agents↗

[Residue analysis of spectinomycin in tissues of chicken and swine by HPLC].

A reversed-phase HPLC method with ultraviolet detection using p-nitrophenyl hydrazine as a pre-column derivatizing reagent was investigated for the determination of the antibiotic spectinomycin (SPCM) in muscle, liver, kidney and fat of chicken and swine. SPCM was extracted from samples with 10% trichloroacetic acid saturated with EDTA-2Na, and then cleaned up with coupled Sep-Pak Plus PS-2 cartridges. The detection limit of SPCM was 0.02 microgram (potency)/g. Recoveries of SPCM ranged from 77.4 to 97.4% for chicken tissues and from 74.5 to 91.8% for swine tissues. The present method was used for the analysis of chicken tissues after the 11th day of withdrawal (SPCM-medicated drinking water: 500 mg (potency)/L, for 7 days), and swine tissues after the 14th day of withdrawal (SPCM-medicated feed: 100 mg (potency)/kg, for 7 days). Results showed that SPCM concentrations were lower than the MRLs in all tissues.

Animals↗

Spectinomycin modification. III Chloro-deoxy analogs.

9-Epichloro-9-deoxy-4(R)-dihydrospectinomycin (3), 9-chloro-9-deoxy-4(R)-dihydrospectinomycin (7), 9-deoxy-8, 9-epimino-4(R)-dihydrospectinomycin (6), and 9-epichloro-9-deoxy-spectinomycin (10) have been prepared and their structures established by proton magnetic resonance. These analogs are devoid of antibiotic activity.

Bacteria↗

Modification of spectinomycin. 2. Derivatives of 4-dihydro-4-deoxy-4(R)-aminospectinomycin.

Acyl derivatives 5a approximately j and alkyl derivatives 7a approximately r of 4-dihydro-4-deoxy-4(R)-aminospectinomycin (1a) were prepared and tested for antibacterial activity. Only acyl compounds derived from long chain aliphatic acids showed activity in vitro, but were inactive when tested in vivo. All alkyl derivatives were active in vitro. In vivo however only the short chain derivatives 7a approximately c were active. Compound 7b showed higher activity than spectinomycin.

Bacteria↗

Enzymatic adenylylation of spectinomycin by Acinetobacter calcoaceticus subsp. anitratus.

Spectinomycin (SPC) was inactivated in the presence of adenosine-5'-triphosphate and magnesium ion by an enzyme preparation made from Acinetobacter calcoaceticus subsp. anitratus GN12313 resistant to both SPC and streptomycin. The structure of the inactivated SPC was found to be the adenylylated product of the hydroxy group on C-9 of the actinamine moiety.

Acinetobacter↗