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PubMed1974

Therapeutic effect of lincomycin and spectinomycin water medication on swine dysentery.

The therapeutic effects of various water medications on swine dysentery were determined in 223 pigs under controlled conditions. Carrier pigs were mixed with test animals until the disease was established. Lincomycin (22 mg/liter), spectinomycin (44 mg/liter) alone and lincomycin and spectinomycin in combination (66 mg/liter) and sodium arsanilate (161 mg/liter) in drinking water for seven days were the drugs evaluated. Negative and positive controls were also included. The experiment was terminated 41 to 43 days after initial medication. Mortality, mean value for stool consistency, incidence of dysenteric days and gross lesions of swine dysentery were the parameters measured for each treatment group.The lincomycin-spectinomycin water medication was effective for the treatment of swine dysentery. Pigs treated with lincomycin-spectinomycin had a higher survival rate, a lower incidence of dysenteric days and fewer gross lesions of swine dysentery than pigs treated with sodium arsanilate, lincomycin or spectinomycin alone or the infected controls (P < 0.05).

Animals↗
PubMed1979

[Serum concentration and kinetics after i.v.-infusion of 3 g lincomycin (author's transl)].

The pharmacokinetics of lincomycin (Albiotic) were studied in ten healthy male and female volunteers after administration of 1 X 3 g and 2 X 3 g lincomycin i.v., respectively, infused over 60 min. After discontinuing the infusion a mean serum value of lincomycin of 97.5 microgram/ml was measurable. 5 h later the mean serum values were 13.5 microgram/ml and 24 h later 1.6 microgram/ml. After 24 h 72.5% of the drug had been eliminated in the urine of 4 volunteers. The mean serum half-life was 286.3 min with the one-compartment model. The volume of distribution was 78.7 l with the one-compartment model and 25.9 l with the two-compartment model. The area under the curve has the value of 14 805.39 microgram . min . ml-1 and 44 418.9 microgram . min. ml-1 with the one- and two-compartment model, respectively. The mean values for the total renal clearance with the two models were 204.8 and 75.5 ml/min. The importance of high-dose therapy with lincomycin is discussed with respect to the tissue penetration of the substance and possible bactericidal effects, whereas lincomycin in general only acts bacteriostatic.

Adult↗
PubMed1978

[Action of lincomycin, chymotrypsin and their combinations on the course of experimental staphylococcal infection].

The culture of Staphylococcus aureus was administered intraperitoneally in a dose of LD30 to albino mice. The animals of the 1st, 2nd and 3rd groups were treated with lincomycin, chymotripsin and combination of lincomycin with chymotripsin respectively. The animals of the 4th group were used as control and were not subjected to the treatment with the drugs. A part of the animals from every group was killed on the 3rd, 7th, 14th, 21st and subsequent days and their organs were investigated microscopically and bacteriologically. It was found that staphylococci was isolated from the control mice during a 50-day period after inoculation. Complete liberation of the organs from the causative agent within 25 days from the beginning of the experiment was registered in the animals treated with lincomycin. Isolation of the staphylococci was over by the 27th day in the animals treated with chymotrypsin. Liberation of the organs from the causative agent by the 17th day was observed in the albino mice treated with the combination of lincomycin with chymotrypsin. The combined use of lincomycin with chymotrypsin proved to be most effective: no death was registered among the albino mice, the levels of the pathogenicity and antibiotic resistance in the pathogenic staphylococci decreased.

Animals↗
PubMed1981

[Use of selective media with lincomycin for the directed screening of antibiotic producers].

Relation between lincomycin resistance of Micromonospora cultures freshly isolated from soil samples and their capacity for production of antibiotics related to lincomycin by the structure or mode of action was shown. 32 cultures of Micromonospora were isolated from soil platings containing 50--100 microgram/ml of lincomycin. Crude antibiotic substances were recovered with the method of organic solvent extraction from 10 cultures possessing pronounced antibiotic activity. Selective inactivity (MIC more 1000 microgram/ml) of the crude substances with respect to the lincomycin resistant variant of Staph. aureus 209 p was observed, 2 of them having no inhibitory effect on the erythromycin resistant variant of the staphylococcus. The crude antibiotics inhibited the growth of the initial strain of the staphylococcus and its other antibiotic resistant variants in concentrations of 0.5--10 microgram/ml. It was demonstrated with the use of gas chromatography and mass spectrometry that one substance was lincomycin and 4 substances were known macrolides. Efficiency of the simple method of directed screening of antibiotics belonging to definite groups is indicated. Resistance of actinomycetes freshly isolated from natural substrates to various antibiotics is used as the criterion for antibiotic screening. The method provides detection of various antibiotics which are analogs in the structure or mode of action of the selecting antibiotic used for the screening.

Anti-Bacterial Agents↗
PubMed1978

Use of gentamicin to prevent intestinal side effects of lincomycin therapy.

Mild to severe and persisting diarrhea and even colitis have been reported as a side effect of therapy with lincomycin and clindamycin. An alteration in the normal bowel flora with an overgrowth of coliforms and other antibiotic-resistant bacteria has been postulated as a mechanism for the development of diarrhea. Investigations were undertaken in men to observe whether the simultaneous administration of gentamicin was capable of preventing lincomycin-associated intestinal disturbances. Of the 30 subjects treated only with lincomycin 11 (36.6%) developed diarrhea. Of the 18 subjects treated with lincomycin and simultaneously with oral gentamicine, none developed diarrhea. Results of bacteriological examinations indicate that in subjects treated with lincomycin, some potentially pathogenic bacteria, like coliforms and clostridia, are still present in intestinal flora; the simultaneous absence of bifidobacteria and bacteriodes could result in the abolishment of the host resistance to the noxious activity of these endogenous bacteria, as some reported data of the literature suggest. Coliforms and the majority of clostridia strains are not present in subjects treated simultaneously with gentamicin.

Adult↗
PubMed1980

[Effect of lincomycin, chymotrypsin and their combinations on the splenic plasmacytic reaction and the antibody titer in experimental staphylococcal infection].

The effect of lincomycin, chymotrypsin and their combinations on the plasmocytic reaction of the spleen and agglutinin titer in mice with experimental staphylococcal infection was studied. The infected mice were divided into 4 groups: the 1st group included untreated infected animals, the 2nd, 3rd and 4th groups consisted of the mice treated with lincomycin, chymotrypsin and their combinations respectively. Lincomycin and chymotrypsin were used in doses of 150 and 2 mg/kg respectively. By the 3rd, 7th, 14th and 21st day of the infection and treatment the animals were decapitated, th blood was collected for determination of the staphylococcal agglutinin titers in the serum, the spleens were removed for investigation of the plasmocytic reaction. It was shown that the treatment of the experimental staphylococcal infection with lincomycin resulted in decreased proliferation of the plasmatic cells and antibody formation. The use of chymotrypsin resulted in increased proliferation of the plasmatic cells and specific antibody titer. The use of chymotrypsin in conjunction with lincomycin lowered the suppressing effect of the latter on the above indices.

Animals↗
PubMed1976

Unfavorable effect of atropine-diphenoxylate (Lomotil) therapy in lincomycin-caused diarrhea.

In this double-blind, randomized study, 200 normal subjects received a three-day course of one of five treatment regimens: lincomycin hydrochloride monohydrate injection (sterile solution, 300 mg/ml) with two tablets of either placebo, a mixture of atropine sulfate and diphenoxylate hydrochloride (Lomotil), an aspirin-phenacetin-caffeine (APC) combination or the latter with codeine, or an injection of saline with two placebo tablets. Gastrointestinal irritation was most prominent in subjects receiving lincomycin with atropine-diphenoxylate and lincomycin with APC plus codeine (P less than .05). Decreased intestinal motility from atropine-diphenoxylate or codeine may increase the contact time between the lincomycin (or its metabolites) or some developing toxic substances and the mucosal epithelium. The use of atropine-diphenoxylate or codeine in treating lincomycin-induced diarrhea may be questionable.

Administration, Oral↗
PubMed1977

[Optimal regime of intravenous administration of lincomycin in osteomyelitis].

The pharmacokinetics of lincomycin in the blood of 8 patients with osteomyelitis was studied on the drug single and uninterrupted intravenous administration in therapeutic doses. It was found that when the antibiotic was administered continuously according to the routine scheme, its therapeutic blood levels were attained only 1.5 hours after the drug infusion. The optimal regimen of lincomycin uninterrupted infusion providing its constant rate in combination with the single intravenous administration was estimated with the help of the constants of the two-compartment model of lincomycin pharmacokinetics. According to the calculations the rate of the antibiotic administration necessary for providing therapeutic levels should be 2.2 mg/kg in complex with the loading dose equal to 5.4 mg/kg. Practical trials showed that intravenous administration of lincomycin with the above regimen remained within therapeutic range already 10 to 20 minutes after the beginning of the drug infusion. Therefore, from the pharmacokinetic point of view the recommended regimen for lincomycin infusion should be considered preferable to that used presently.

Adolescent↗
PubMed1976

[Pharmacokinetics and enzymatic transformations of 35S-lincomycin in the tissues of certain organs].

Pharmacokinetics of 35S-lincomycin was studied with the microbiological and radiometric methods of the antibiotic determination. Significant deviations in the results obtained with the two methods in determination of lincomycin levels in the liver and kidneys were observed. The values obtained with the radiometric method were 10 times higher than those obtained with the microbiological method. Paper radiochromatography of the extracts from the liver and kidneys of the animals treated with 35S-lincomycin revealed the presence of not only 35S-lincomycin, but also a number of the label containing substances, the products of the antibiotic enzymatic transformation. Radiochromatography of the extracts from the brain of the animals treated with 35S-lincomycin revealed several peaks of radioactivity against the back ground of low levels of the label.

Animals↗
PubMed1994

Mutations conferring lincomycin, spectinomycin, and streptomycin resistance in Solanum nigrum are located in three different chloroplast genes.

A number of Solanum nigrum mutants resistant to the antibiotics spectinomycin, streptomycin and lincomycin have been isolated from regenerating leaf strips after mutagenesis with nitroso-methylurea. Selection of streptomycin- and spectinomycin-resistant mutants has been described earlier. Lincomycin-resistant mutants show resistance to higher levels of the antibiotic than used in the initial selection, and in the most resistant mutant (L17A1) maternal inheritance of the trait was demonstrated. The lincomycin-resistant mutant L17A1 and a streptomycin plus spectinomycin resistant double mutant (StSp1) were chosen for detailed molecular characterisation. Regions of the plastid DNA, within the genes encoding 16S and 23S rRNA and rps12 (3') were sequenced. For spectinomycin and lincomycin resistance, base changes identical to those in similar Nicotiana mutants were identified. Streptomycin resistance is associated with an A-->C change at codon 87 of rps12 (converting a lysine into a glutamine), three codons upstream from a mutation earlier reported for Nicotiana. This site has not previously been implicated in streptomycin resistance mutations of higher plants, but has been found in Escherichia coli. The value of these mutants for studies on plastid genetics is discussed.

Base Sequence↗
PubMedDate not supplied

[Antibacterial activity of clindamycin and lincomycin in broth, serum, and in combination with polymorphonuclear leukocytes against Staphylococcus aureus and Staphylococcus epidermidis].

We investigated the antibacterial activity of clindamycin and lincomycin at 1/4 X minimum inhibitory concentration (MIC), 1 X MIC and 4 X MIC against a serum-resistant Staphylococcus aureus and a serum-resistant Staphylococcus epidermidis strain in broth, in serum with and without the presence of leukocytes and in Hank's medium in combination with leukocytes alone. Against both test strains, lincomycin in broth and serum was similarly effective, whereas against S. aureus clindamycin in broth was somewhat more active. In the combined test mixture of serum with leukocytes, even a 1/4 X MIC of clindamycin or lincomycin markedly improved leukocyte killing of S. aureus, whereas both compounds could not further enhance the marked leukocyte killing of S. epidermidis, even at inhibitory concentrations. In Hank's medium with leukocytes alone, clindamycin and lincomycin had at the most only a bacteriostatic effect against both test strains.

Blood↗
PubMed1992

Slow-onset inhibition of ribosomal peptidyltransferase by lincomycin.

In a system derived from Escherichia coli, we carried out a detailed kinetic analysis of the inhibition of the puromycin reaction by lincomycin. N-Acetylphenylalanyl-tRNA (Ac-Phe-tRNA; the donor) reacts with excess puromycin (S) according to reaction [1], C+S Ks <--> CS k3 --> C'+P, where C is the Ac-Phe-tRNA-poly(U)-ribosome ternary complex (complex C). The entire course of reaction [1] appears as a straight line when the reaction is analyzed as pseudo-first-order and the data are plotted in a logarithmic form (logarithmic time plot). The slope of this straight line gives the apparent ksobs = k3[S]/(Ks + [S]). In the presence of lincomycin the logarithmic time plot is not a straight line, but becomes biphasic, giving an early slope (ke = k3[S]/(Ks(1 + [I]/Ki) + [S])) and a late slope (k1 = k3[S]/(Ks(1 + [I]/K'i + [S])). Kinetic analysis of the early slopes at various concentrations of S and I shows competitive inhibition with Ki = 10.0 microM. The late slopes also give competitive inhibition with a distinct inhibition constant K'i = 2.0 microM. Excluding alternative models, the two phases of inhibition are compatible with a model in which reaction [1] is coupled with reaction [2], C+I k4 <--> k5 CI k6 <--> k7 C*I, where the isomerization step CI <--> CI* is slower than the first step C+I <--> CI, Ki = k5/k4 and K'i = Ki [k7/(k6 + k7)]. Corroborative evidence for this model comes from the examination of reaction [2] alone in the absence of S. This reaction is analyzed as pseudo-first-order going toward equilibrium with kIeq = k7 + (k6 [I]/(Ki + [I])). The plot of kIeq versus [I] is not linear. This plot supports the two-step mechanism of reaction [2] in which k6 = 5.2 min-1 and k7 = 1.3 min-1. This is the first example of slow-onset inhibition of ribosomal peptidyltransferase which follows a simple model leading to the determination of the isomerization constants k6 and k7. We suggest that lincomycin inhibits protein synthesis by binding initially to the ribosome in competition with aminoacyl-tRNA. Subsequently, as a result of a conformational change, an isomerization occurs (CI <--> C*I), after which lincomycin continues to interfere with the binding of aminoacyl-tRNA to the isomerized complex.

Binding, Competitive↗
PubMed1994

Lincomycin and spectinomycin in the treatment of breeding rams with semen contaminated with ureaplasmas.

Ureaplasma species were isolated from semen samples collected sequentially from one Awassi and three Assaf breeding rams. Each ram was injected subcutaneously with an aqueous solution of lincomycin and spectinomycin for five consecutive days at a dose equivalent to 4.5 mg kg-1 lincomycin and 9.0 mg kg-1 spectinomycin daily. Serum and semen samples were collected at intervals during the treatment and assayed for lincomycin. No Ureaplasma species were isolated from semen samples collected during the course of the treatment and at intervals for 17 days after the last treatment. The concentration of lincomycin in semen ranged from 0.51 microgram ml-1 four hours after treatment to 0.08 microgram ml-1 24 hours after treatment, and these levels were three to nine times higher than the corresponding serum concentrations.

Animals↗
PubMed2003

Determination of lincomycin and tylosin residues in honey using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

An analytical method for the determination of residues of the antibiotic drugs lincomycin and tylosin in honey was developed. The procedure employed a solid-phase extraction for the isolation of lincomycin and tylosin from diluted honey samples. The antibiotic residues were subsequently analyzed by reversed-phase HPLC with atmospheric pressure chemical ionization mass spectrometric detection. Average analyte recoveries for lincomycin and tylosin ranged from 84 to 107% in replicate sets of honey samples fortified with drug concentrations of 0.01, 0.5, and 10 microg/g. The method detection limits were determined to be 0.007 and 0.01 microg/g for lincomycin and tylosin, respectively.

Atmospheric Pressure↗
PubMed1996

Determination of lincomycin residues in salmon tissues by gas chromatography with nitrogen-phosphorus detection.

A sensitive method for the determination of lincomycin residues in fish tissues is described. Lincomycin was extracted from fish tissues with phosphate buffer (pH 4.5). The extract was concentrated with a C18 solid-phase extraction cartridge and further cleaned up by solvent extraction. Lincomycin was derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide to form a trimethylsilyl derivative before being analyzed by gas chromatography with nitrogen-phosphorus detection. Coumaphos was used as the internal standard. Assays showed good linearity in the range 25-250 ppb (ng/g) (r = 0.9994). Recoveries of fortified lincomycin at 50, 100 and 200 ppb were > 80% with relative standard deviations < 6%. The limit of detection of the method was 1.7 ppb and the limit of quantitation was 3.8 ppb.

Acetamides↗
PubMed2004

Quantitative analysis of lincomycin in animal tissues and bovine milk by liquid chromatography electrospray ionization tandem mass spectrometry.

A sensitive method for determining lincomycin in bovine milk, animal muscles and organs using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) is presented. Milk and homogenized animal tissues were extracted with acetonitrile twice after addition of an appropriate amount of clindamycin, a lincosamide analogue as the internal standard. The combined extracts were finally made up to 10 ml with distilled water and partitioned with hexane to remove the animal fats prior to analysis. Analytes in the extracts were separated on a reversed phase C18 column (250 mm x 2.1 mm, 5 microm) using a mobile phase of a 3:7 (v/v) mixture of 0.1% formic acid in acetonitrile and an ammonium formate buffer (ammonium formate:formic acid:acetonitrile:water, 1:5:50:950, v/v/v/v) running at a flow rate of 0.2 ml min(-1). Presence of lincomycin was confirmed by the presence of two characteristic product ions at m/z 126.1 and 359.2 within a defined retention time window from the precursor ion at m/z 407.2, whilst quantification was based on the relative ratio of the sum of the peak areas at m/z 126.1 and 359.2 for lincomycin to that of the internal standard (peaks at m/z 126.1 and 377.2) with reference to the respective ratios of the calibration standards. The validated method that was found to have linear responses in the calibration range from 25 to 3000 microg kg(-1) and satisfactory intra-day and inter-day accuracy (94.4-107.8%) and precision (1.3-7.8%) at concentrations ranging from 100 to 1500 microg kg(-1) has been applied to real samples and matrix spiked samples. It is considered robust and suitable for analysis of lincomycin in milk and animal tissues.

Animals↗
PubMed1979

Clindamycin and lincomycin alter miniature endplate current decay.

Antibiotic-induced muscle paralysis has frequently been found in both experimental animals and man with three distinct classes of antibiotic: (1) streptomycin and related aminoglycoside compounds, (2) polymyxins and (3) tetracyclines. Recently lincomycin and its chemical congener, clindamycin, have been reported to produce muscle paralysis which has different characteristics from those seen with other classes of antibiotic. Although closely related in chemical structure, lincomycin and clindamycin also seem to produce muscle paralysis by different mechanisms. Clindamycin is considered to exert a direct depressant action on muscle contractility whereas the action of lincomycin is considered to be primarily a depression of neuromuscular transmission. We report here that each of these antibiotics had a significant but different influence on endplate channel behaviour. Clindamycin increased the rate of miniature endplate current (m.e.p.c.) decay and reduced its voltage sensitivity without altering its exponential nature. Lincomycin split m.e.p.c. decay into an initial rapid phase followed by a prolonged phase.

Animals↗
PubMed1984

Selective inhibition of enzyme synthesis by lincomycin in Staphylococcus aureus.

The effect of subinhibitory concentrations of lincomycin on the production of lipase, coagulase and alpha-haemolysin by one lincomycin-resistant strain of Staphylococcus aureus was investigated. The highest concentration of lincomycin, which had little effect on growth, completely inhibited enzyme and haemolysin formation. The antibiotic at the concentrations used did not inactivate enzymes. Lincomycin caused no intracellular accumulation of these products, indicating a possible effect on enzyme and haemolysin synthesis. Subinhibitory concentrations of erythromycin and chloramphenicol showed no effect on enzyme and haemolysin formation.

Drug Resistance, Microbial↗