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PubMed1981

Therapeutic effects of parenteral administration of lincomycin on experimentally transmitted swine dysentery.

The therapeutic effects of 2 dose levels of lincomycin and a reference drug (tylosin) were compared in 80 growing pigs with experimentally transmitted swine dysentery (SD). The pigs were allotted equally to 4 groups. Treatment was initiated 5 days after pigs were exposed to SD. Lincomycin was administered IM at doses of 11.0 or 4.4 mg/kg of body weight once daily for 3 to 7 days. Tylosin was injected IM at a dose of 8.8 mg/kg once daily for 3 days (highest recommended dose). The control (nontreated) infected pigs were not given the drug. The effects was terminated 22 days after exposure to SD. The effects were measured in terms of mortality, survival, physical activity, performance, and necroscopy findings. The 2 drugs reduced the clinical signs of SD. Pigs treated with either dose of lincomycin had a better treatment response than did pigs treated with tylosin, as evidenced by less mortality, longer survival time, and greater feed intake (P = 0.05). In addition, pigs treated with the larger dose of lincomycin, 11.0 mg/kg, had better treatment responses in 12 of the 14 measured criteria than did pigs treated with tylosin. Also, these pigs treated with the larger lincomycin dose had better treatment responses tha did the pigs treated wih the smaller dose of lincomycin, 4.4 mg/kg, as evidenced by dysentery, fecal consistency, physically active and intermediately active pig days, body weight gain, and feed intake.

Animals↗
PubMed1976

Sensitivity of Escherichia coli after exposure to lincomycin in vitro and in vivo.

Exposure of 10 Escherichia coli isolates in vitro to a concentration of lincomycin found in the intestine of swine fed the maximun concentration recommended in feed did not significantly affect sensitivity to 8 antibiotics, 1 nitrofuran, and 1 sulfonamide when compared with sensitivity of E coli isolates not exposed to lincomycin. Changes in sensitivity, on the basis of Kirby-Bauer interpretation, did occasionally occur; however, these alterations were in zonal sizes, which were marginal for designation as sensitive, intermediate, or resistant. These same fluctuations were observed in E coli not exposed to lincomycin. Exposure of E coli to lincomycin in the intestinal tract of swine for 34 days did not alter sensitivity of E coli to tetracycline, dihydrostreptomycin, spectinomycin, lincomycin, or triple sulfa. The results indicated that addition of lincomycin to the feed did not appear to promote resistance transfer in E coli.

Ampicillin↗
PubMedDate not supplied

Determination of lincomycin residue in salmon tissues by ion-pair reversed-phase liquid chromatography with electrochemical detection.

A method is described for detecting and quantitating lincomycin residue in salmon muscle and skin tissues by ion-pair reversed-phase liquid chromatography (LC) with electrochemical detection at +0.9 V. Lincomycin was extracted from tissues by homogenizing with 0.01 M KH2PO4 buffer (pH 4.5) and centrifuging the mixture. Water-soluble proteins were precipitated by adding sodium tungstate and sulfuric acid and removed by centrifugation. The buffer extract was then passed through a C18 solid-phase extraction cartridge. Lincomycin was eluted with 50% acetonitrile in water, and the eluate containing lincomycin was extracted with ethyl acetate. After the solvent had evaporated, the residue was redissolved in mobile phase and analyzed by LC. The method had a limit of detection of 7 ng/g lincomycin for salmon muscle and 12 ng/g for salmon skin. The limit of quantitation was 17 ng/g for salmon muscle and 24 ng/g for salmon skin. Average recoveries of lincomycin spiked at 50, 100, and 200 ng/g were > or = 85% for salmon muscle and > or = 80% for salmon skin.

Acetonitriles↗
PubMed1981

Lincomycin serum and saliva concentrations after intramuscular injection of high doses.

Serum and saliva levels of lincomycin were determined in 15 normal adult male volunteers after a single intramuscular injection of 600, 1000, or 1500 mg lincomycin in a three-way crossover study. The area under the serum concentration-time curve did not increase in proportion to the increase in dose. The increase in concentration of lincomycin in saliva was greater than expected for the increase in dose. There were not significant differences in elimination half-life between doses. These results suggest that the apparent clearance of lincomycin increases with increasing dose possibly because of a decrease in serum protein binding of lincomycin at high serum concentrations.

Adult↗
PubMed1985

Evaluation of lincomycin as a cholesterol gallstone dissolution rate accelerator.

These studies were undertaken to test the hypothesis that interfacial resistance may be an important rate-limiting factor in cholesterol gallstone dissolution. The addition of lincomycin hydrochloride to the gallbladder bile of dogs in an in vitro bath system resulted in an acceleration in the rate of dissolution of a compressed cholesterol monohydrate pellet incubating in the bile. However, the constant infusion of lincomycin for 13 d directly into the gallbladders of conscious, unrestrained dogs, which resulted in biliary lincomycin concentrations comparable to that of the in vitro tests, did not alter the dissolution rate of a compressed cholesterol monohydrate pellet which had been surgically placed into the gallbladder. We therefore conclude that the interfacial resistance between the cholesterol monohydrate pellet and the bile may be reduced by the addition of lincomycin to the gallbladder bile which, in the in vitro environment, results in an acceleration in the rate of dissolution of compressed cholesterol pellets. However, the ineffectiveness of lincomycin in accelerating the dissolution of cholesterol pellets in vivo suggests that interfacial resistance is not the only rate-limiting factor in gallstone dissolution. Other factors, such as mixing, may also be critical.

Animals↗
PubMed2006

High-throughput quantification of lincomycin traces in fermentation broth of genetically modified Streptomyces spp. Comparison of ultra-performance liquid chromatography and high-performance liquid chromatography with UV detection.

A new separation and quantification method using ultra-performance liquid chromatography (UPLC) with UV detection was developed for detection of lincomycin traces in fermentation broth of different Streptomyces spp. A similar high-performance liquid chromatography (HPLC) protocol was simultaneously developed for comparison purposes. Both methods were validated and showed a linear range of detector response for quantification of lincomycin in concentration from 3.125 to 1000.0 microgml(-1) with correlation coefficient 0.999 and recoveries ranging from 81.5 to 89.85% with precision < or =5%. Compared with the HPLC, the UPLC method offered high sample throughput and about 10 times lower consumption of solvents. The developed assays were used for determination of lincomycin production in genetically manipulated production strain Streptomyces lincolnensis and for determination of lincomycin production after heterologous expression of lincomycin biosynthetic gene cluster in non-producing strain Streptomyces coelicolor.

Chromatography, High Pressure Liquid↗
PubMed2005

HPLC determination of lincomycin in premixes and feedstuffs with solid-phase extraction on HLB OASIS and LC-MS/MS confirmation.

A rapid clean-up procedure based on solid-phase extraction (SPE) and HPLC determination of lincomycin in premixes with UV detection is described. After extraction of lincomycin from premix with extraction solvent the extract is applied to OASIS HLB column treated with methanol and water. Lincomycin is eluted with methanol and effluent is analysed on analytical column (phenyl) using mobile phase consists 0.2% phosphoric acid in water and acetonitrile (875:125, v/v). Detection is performed at 208 nm. Quantitation is carried out using external standard. The mean recovery of lincomycin was 105.0+/-7.3%, in concentration range of 250-750 mg kg(-1), and 99.8+/-3.7%, in concentration range of 10,000-150,000 mg kg(-1). The limit of determination, based on a signal-to-noise ratio of 10:1, was 5.2 mg kg(-1). LC-MS/MS confirmation of lincomycin is also presented. Identification was performed by monitoring two pairs of multiple reaction monitoring ions from the parent ions (m/z 407.2-->126.1 and 407.2-->359.2) at the defined retention time window and by matching of the specific tolerance of relative abundance of major ions as stated in the European Union Commission Decision 2002/657/EC.

Animal Feed↗
PubMed1993

Different kinetic of enzymatic inactivation of lincomycin and clindamycin in Staphylococcus aureus.

Lincosamide inactivation nucleotidylation (Lin) enzyme determined by the pBI109PGL plasmid of Staphylococcus epidermidis exhibits high level resistance to lincomycin but sensitivity to clindamycin by standard susceptibility methods. Substrate profile determination showed clindamycin to be a better substrate for the enzyme than lincomycin. In cultures of the plasmid-harboring strain, the level of clindamycin decreased below the inhibitory concentration in the first 4 hours of incubation but the level of lincomycin persisted longer. The initial extended inhibitory effect of clindamycin is due to better membrane penetrating ability, resulting in a higher intracellular concentration than that of lincomycin. Moreover, energy-dependent reduction in clindamycin uptake, probably due to active efflux of clindamycin but not of lincomycin, was observed. A therapeutic effect of clindamycin is not expected in infections caused by Lin-producer strains because the bacteriostatic effect of the drug is rapidly eliminated after administration.

Biotransformation↗
PubMed1977

Plasma, bone, hip capsule, synovial and drain fluid concentrations of lincomycin during total hip replacement.

1 Lincomycin (600 mg) was given 6 h preoperatively by intramuscular injection, as an intravenous infusion over 30 min and for 72 h postoperatively in twelve patients having total hip replacement. 2 The plasma, bone, hip capsule, synovial and drain fluid concentrations of lincomycin were almost always above the M.I.C. of lincomycin against penicillinase producing Staphylococcus aureus. 3 There was a good correlation between the estimated concentrations of lincomycin in bone by the grinding and agitation methods of analysis. 4 Two patients developed pseudomembranous colitis after parenteral lincomycin.

Adult↗
PubMed1999

Slow sequential conformational changes in Escherichia coli ribosomes induced by lincomycin: kinetic evidence.

In a cell-free system derived from Escherichia coli, lincomycin produces biphasic logarithmic time plots for inhibition of peptide-bond formation when puromycin is used as an acceptor substrate and AcPhe-tRNA as a donor substrate. In a previous study, initial slope analysis of the logarithmic time plots revealed that the encounter complex CI between the initiator ribosomal complex (C) and lincomycin (I) undergoes a slow isomerization to C*I. During this change, the bound AcPhe-tRNA and lincomycin are rearranged to also accommodate puromycin, and this may account for the mixed noncompetitive inhibition (K(i)* = 70 microM) established at higher concentrations of the drug. The above-mentioned effect was further investigated by analyzing the late phase of the logarithmic time plots. It was found that C*I complex reacts with a second molecule of I, giving C*I(2) complex. However, the logarithmic time plots remain biphasic even at high concentrations of lincomycin, making possible the identification of another inhibition constant K(i)*', which is equal to 18 microM. The simplest explanation of this finding is to assume the existence of a second isomerization step C*I(2) <--> C*I(2'), slowly equilibrated. The determination of K(i)*' enables us to calculate the isomerization constant (K(isom) = 2.9) with the formula K(i)*' = K(i)*/(1 + K(isom)). Our results suggest that whenever a fast and reversible interaction of lincomycin with the elongating ribosomal complex C occurs, the latter undergoes a slow isomerization, which may be the result of conformational changes induced by the drug.

Anti-Bacterial Agents↗
PubMed1989

Lincomycin increases the half-life of beta-lactamase mRNA.

Escherichia coli K-12 strains isolates carrying plasmid pBR322 were grown in the presence of subinhibitory concentrations of lincomycin, which stimulated beta-lactamase synthesis about 2.5-fold, and the effects of the drug on the synthesis and degradation of bla mRNA were studied. The bla mRNA levels determined by 1-min pulse-labeling with [3H]uridine were significantly higher in a lincomycin-containing culture than in the control culture, indicating that stimulation of beta-lactamase synthesis is caused by an increase in the amount of bla mRNA. The enhancing effect of lincomycin was observed in strains harboring pBR322 delta P1 and pBR322 delta P3, which lacked the P1 or P3 promoter, respectively, as well as in the strain harboring pBR322. S1 nuclease analysis showed that the half-life of bla mRNA increased about 2.7-fold when lincomycin was present. These results indicate that the increase in beta-lactamase synthesis caused by lincomycin is due to an increase in the stability of bla mRNA rather than activation of its synthesis.

Coliphages↗
PubMed1976

Characterization of the neuromuscular block produced by clindamycin and lincomycin.

The site of neuromuscular blockade induced by clindamycin and lincomycin was studied on isolated nerve and nerve-muscle preparations. Clindamycin (3.6 X 10(-3) M) but not lincomycin (up to 1.5 X 10(-2) M) had a local anaesthetic effect on a frog desheathed nerve preparation. Clindamycin (8 X 10(-4) M) and lincomycin (4 X 10(-3) M) depressed the response of the rat diaphragm to nerve stimulation and to direct muscle stimulation in parallel. This indicated that the predominant neuromuscular blocking effect of these antibiotics was due to an effect on the muscle. Clindamycin was fivefold more potent than lincomycin in this effect, and the unionized form of both drugs was the active form. Lincomycin (4 X 10(-3) M) but not clindamycin (8 X 10(-4) M) also had some depressant effect on nerve-muscle transmission as indicated by the interaction of the effects of the antibiotics and d-tubocurarine. The significance of these findings is discussed in relation to the acute clinical toxicity of these antibiotics.

Animals↗
PubMed2003

The effects of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim on hyaluronidase activities and sperm characteristics of rams.

The effects of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim combinations on the hyaluronidase enzyme of serum and semen and on sperm characteristics in rams were determined. Thirthy-two Akkaraman rams were used. The rams were randomly divided into four groups. Group A and group B were determined as control groups of group C (lincomycin-spectinomycin) and D (sulfamethoxazole-trimethoprim), respectively. Combinations of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim were administered at doses of 15 mg.kg(-1) intramuscularly and 12 mg.kg(-1) body weights orally, respectively. Blood and semen samples were collected at 4, 12, 24, 48, 72, 192 and 384 hr. Semen hyaluronidase activities of rams in group C increased significantly (p<0.001, <0.05) compared with the control group at 24 and 48 hr, respectively. Semen hyaluronidase activities in group D rams also increased significantly (p<0.001) in comparison with the control group at all times except 72 and 384 hr. Serum hyaluronidase activities increased significantly (p<0.01, <0.001) at 24 and 48 hr after treatment of lincomycin-spectinomycin. Additionally, significant (p<0.05, <0.001) increases were detected in the serum hyaluronidase activities of group D at 48 and 72 hr, respectively. No significant correlation was found between serum and semen hyaluronidase activities. Furthermore, significant increases (p<0.05) were observed in the percentages of motile sperm in the rams of group C and D compared with the control groups. The values of sperm concentration and total number of sperm in group C and D rams decreased significantly (p<0.001) in comparison with control groups. No significant correlations were found between the semen hyaluronidase activities and sperm characteristics. In conclusion, these findings show that the combinations of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim do not have any harmful effects on hyaluronidase activities and sperm motility. However, the use of both antibiotic combinations in breeding rams during the ramming season is not advisable due to the decrease of sperm concentration.

Animals↗
PubMed2005

Macrolides and lincomycin susceptibility of Mycoplasma hyorhinis and variable mutation of domain II and V in 23S ribosomal RNA.

A total of 151 strains of Mycoplasma hyorhinis isolated from porcine lung lesions (weaned pigs, n=71, and finishers, n=80) were investigated for their in vitro susceptibility to 10 antimicrobial agents. Thirty-one strains (28 from weaned pigs and 3 from finishers) showed resistance to 16-membered macrolide antibiotics and lincomycin. The prevalence of the 16-membered macrolide-resistant M. hyorhinis strain in weaned pigs from Japanese herds has approximately quadrupled in the past 10 years. Several of the 31 strains were examined for mutations in the 23S ribosomal RNA (rRNA). All field strains tested showed a transition of A to G at position 2059 of 23S rRNA-rendered Escherichia coli. On the other hand, individual tylosin- and lincomycin-resistant mutants of M. hyorhinis were selected in vitro from the susceptible type strain BTS7 by 3 to 9 serial passages in subinhibitory concentrations of each antibiotic. The 23S rRNA sequences of both tylosin and lincomycin-resistant mutants were compared with that of the radical BTS7 strain. The BTS7 mutant strain selected by tylosin showed the same transition as the field-isolated strains of A2059G. However, the transition selected in lincomycin showed mutations in domains II and V of 23S rRNA, G2597U, C2611U in domain V, and the addition of an adenine at the pentameric adenine loop in domain II. The strain selected by lincomycin showed an additional point mutation of A2062G selected by tylosin.

Animals↗
PubMed1982

Toxin-induced cell membrane injury in guinea pigs given lincomycin.

Guinea pigs treated with lincomycin developed colitis, acute cholecystitis and abnormalities in red blood cell morphology. The present study was designed to study the production of clostridial toxins after lincomycin treatment. Lincomycin produced abnormalities in conventional but not in germ-free guinea pigs. Clostridium difficile was cultured from cecal contents of conventional guinea pigs treated with lincomycin. Cecal filtrate from sick guinea pigs was subjected to Sepharose 4B-CL and Sephadex G-200 column chromatography, yielding a partially purified toxin. Both cecal filtrate and partially purified toxin samples contained a heat labile substance which was cytotoxic to human lung fibroblast Wl-38 cells, and which was neutralized by Clostridium sordelli antitoxin. Toxin samples given orally or intraperitoneally killed normal guinea pigs. Finally, toxin samples induced red cell membrane changes in vitro as well as producing features of acute inflammation in healthy explants of guinea pig cecum and gallbladder in organ culture. Lincomycin treated guinea pigs produced Clostridium difficile toxin(s) which in turn caused diffuse cell membrane injury.

Animals↗
PubMed1977

Efficacy of lincomycin feed medication for the control of necrotic enteritis in broiler-type chickens.

Necrotic enteritis was reproduced in two trials, conducted in a penned research-type broiler facility, by growing broiler-type chickens on litter obtained from a commercial poultry house which had experienced a chronic necrotic enteritis mortality problem. In each trial, various concentrations of lincomycin in feed were evaluated for effectiveness in controlling necrotic enteritis. Lincomycin was evaluated at concentrations of 2 to 100 g./ton in Trial 1 and at concentrations of 2 and 4 g./ton in Trial 2. In each trial, non-lincomycin medicated control groups were also included. Each trial included six treatment groups each consisting of four 60-bird replicates. The coccidiostat used in all groups in Trial 1 and in four of the six treatment groups of Trial 2 was the same as had been used on the farm which the litter had been obtained. No other medications were used in any groups. Clinical coccidiosis due to Eimeria brunetti and E. maxima was prevalent in both trials. Birds receiving lincomycin at a concentration of 2 g./ton, or higher, showed a significant reduction in mortality from necrotic enteritis when compared to birds in coccidiostat-control pens not receiving lincomycin medication. Clostridium perfringens was isolated from the litter in all pens and from the livers of birds dying from necrotic enteritis.

Animals↗
PubMed1998

[The pharmacokinetics of lincomycin when used as a component of a drug combination with ultrahighly dispersed hydroxyapatite].

A drug composition LINCOGAP is assessed, consisting of lincomycin hydrochloride (33%), ultrahighly dispersed hydroxyapatite (HA) (33%), gelatin (7%), and water (27%). Distribution of tritium-labeled lincomycin in organs and tissues of experimental animals was studied by the radiometric method after implantation of the composition into a standard rat mandibular defect. Lincomycin concentration surpassing by orders of magnitude the minimal inhibitory concentration for the main lincomycin-sensitive microorganisms persisted at the site of implantation of the composition for at least 7 days, while the concentration in internal organs and tissues was the minimum. Microbiological findings indicate active diffusion of lincomycin from the site of injection into the adjacent bone. Thus, LINCOGAP exerts an antibacterial effect in the pathological focus while its general toxic effect is low and, therefore, side effects are minimized. Combination of the antibiotic with ultrahighly dispersed HA helps regulate the process of bone repair, stimulating the proliferative and functional activity of osteoblasts. Hence, combined drug LINCOGAP is a promising agent for the treatment of inflammatory destructive diseases of osseous tissue.

Animals↗
PubMed1992

Lincomycin-induced severe colitis in ponies: association with Clostridium cadaveris.

Four groups of two ponies, free of fecal Salmonella and Clostridium cadaveris, were treated as follows: Group A, control group; B, single nasogastrically administered dose of lincomycin (25 mg/kg) followed 48 h later by 3 L of C. cadaveris (10(9) organisms/mL); C, the same dose of lincomycin as group B; D, the same dose of C. cadaveris as group B on each of three occasions at 12 h intervals. Groups A and D remained healthy, but groups B and C developed severe colitis 48-56 h (B) or 72 h (C) after administration of lincomycin. Three ponies were euthanized and one in group B died. Clostridium cadaveris was isolated at about 10(6)/mL of colonic contents from these ponies, but one pony in group B also yielded Salmonella typhimurium from the colon. Subsequent challenge of group A ponies (3 L of C. cadaveris 10(9)/mL, three times at 12 h intervals) did not produce colitis. Nasogastric administration of lincomycin (25 mg/kg) to group A and D ponies, 20 days after administration of C. cadaveris, resulted in severe colitis in all ponies within 48-72 h. Salmonella agona was isolated from the colonic contents of one pony and C. cadaveris (10(6)/mL) from all four ponies. Clostridium cadaveris was not isolated from the colonic content of 45 healthy horses examined immediately after death. These studies confirm the potential for lincomycin to induce severe enterocolitis in ponies and implicate C. cadaveris further as a cause of "idiopathic colitis" in ponies.

Animals↗