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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↗

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↗

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↗

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↗

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↗

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↗

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↗

PubMed1985

Plasmid-mediated resistance to lincomycin by inactivation in Staphylococcus haemolyticus.

Staphylococcus haemolyticus BM4610 was resistant to high levels of lincomycin and susceptible to macrolides, clindamycin, and streptogramins. This resistance phenotype, not previously reported for a human clinical isolate, was due to inactivation of the antibiotic. The gene conferring resistance to lincomycin in strain BM4610 was carried by a 2.5-kilobase plasmid, pIP855, which was cloned in Escherichia coli. Plasmid pIP855 caused inactivation of both lincomycin and clindamycin in S. haemolyticus and in E. coli but conferred detectable resistance to lincomycin only in S. haemolyticus and to clindamycin only in E. coli.

Clindamycin↗

PubMed1975

Susceptibility of various serogroups of streptococci to clindamycin and lincomycin.

The minimal inhibitory concentration of lincomycin and clindamycin for a large number of strains from multiple serogroups of streptococci was determined. The median minimal inhibitory concentration for streptococci from groups A, B, C, F, G, H, L, and M and nongroupable organisms ranged from 0.02 to 0.39 mug of lincomycin per ml and from </=0.01 to 0.09 mug of clindamycin per ml. Among the group D strains, Streptococcus faecium and Streptococcus faecalis were resistant to lincomycin and clindamycin, whereas Streptococcus bovis and four American strains of Streptococcus durans resembled nongroup D isolates in their susceptibility to these agents. Occasional strains of nongroup D streptococci were highly resistant to lincomycin and clindamycin.

Clindamycin↗

PubMed1968

Effect of inoculum size on in vitro susceptibility testing with lincomycin.

There is disagreement in the literature as to whether lincomycin is primarily a bacteriostatic or a bactericidal agent against gram-positive cocci and also regarding the levels of activity of this agent against susceptible microorganisms. These questions were examined in a study of the effect of inoculum size on the results of tube dilution susceptibility determinations with lincomycin against 49 clinical isolates of Staphylococcus aureus and 25 strains of streptococci and pneumococci. Lincomycin was both highly active and bactericidal when tested against 40 strains of S. aureus with inocula containing a maximum of 10(4) cells per ml [median minimal inhibitory concentration (MIC), 0.78 mug/ml; median minimal bactericidal concentration (MBC), 1.56 mug/ml]. With inocula of 10(5) cells per ml, lincomycin was primarily bacteriostatic (median MIC, 1.56 mug/ml; median MBC, 12.5 mug/ml). There were further decreases in inhibitory levels and significant losses of bactericidal activity when inocula containing more than 10(7) cells were tested (median MIC, 3.13 mug/ml; median MBC > 100 mug/ml). Similar measurements with streptococci and pneumococci revealed a lesser effect of inoculum size. The mean MBC value for alpha-hemolytic streptococci increased from 0.40 to 1.05 mug/ml with an increase in inocula from 10(4) to 10(6) cells per ml, but without a marked increase in MIC values. Similar results were obtained for beta-hemolytic streptococci and pneumococci.

Bacteriological Techniques↗

PubMedDate not supplied

Comparative neuromuscular effects of lincomycin and clindamycin.

The effects of lincomycin and clindamycin on neuromuscular transmission in vitro were studied. Standard microelectrode technics were used to measure miniature endplate potential (MEPP) amplitude and frequency, and endplate sensitivity to acetycholine on the frog sartorius muscle. Twitch tension and nerve terminal acetycholine release were also studied. In the drug concentration range where twitch tension changes occurred, both drugs caused marked decreases in MEPP amplitude and decreases in endplate sensitivity to iontophoretically applied acetylcholine. Lincomycin did not alter MEPP frequency but decreased acetylcholine release. Clindamycin increased MEPP frequency and increased acetylcholine release. The study shows that both lincomycin and clindamycin cause blockade of neuromuscular transmission through a postsynaptic action. However, at high concentrations, lincomycin has a nerve-terminal depressant effect, while clindamycin has a marked presynaptic stimulatory effect.

Acetylcholine↗

PubMed1978

Osteomyelitis after operative fracture treatment. A report of 62 cases treated with radical surgery and lincomycin (Lincocin).

During the years 1967--1975 a total of 62 patients were treated for postoperative osteomyelitis. The lower extremities had been fractured in 89 per cent of the cases and 54 per cent were closed injuries. The fractures, mostly caused by traffic accidents and falls, had been immobilized by plates in 30 and by intramedullary nails or pins in 25 patients. Staphylococcus aureus was cultured in 80 per cent, 68 per cent of them were resistant to penicillin, but in 84 per cent the organisms were highly lincomycin sensitive and only three patients with four osteomyelitic lesions presented lincomycin resistance. The treatment consisted chiefly of sequestrectomies and saucerizations supported by 3--12 months of lincomycin treatment. In 30 operations a closed irrigation-suction technique was used, perfusing the wound with lincomycin solution. Stable implants should be left in place until the fracture is clinically solid whereas unstable osteosyntheses should be replaced by rigid internal or extraskeletal fixation. At follow-up, the results were judged as good in 74 per cent, fair 8 per cent and poor 18 per cent. The amputation rate was 13 per cent. Plates should not be used in the treatment of comminuted tibial fractures with considerable soft tissue damage.

Adult↗

PubMed1977

Incidence of antibiotic-related diarrhoea and pseudomembranous colitis: a prospective study of lincomycin, clindamycin and ampicillin.

An existing intensive drug monitoring system was used to study the occurrence of pseudomembranous colitis and diarrhoea in 100 patients treated with lincomycin and clindamycin. In order to give perspective to the results an equal number of matched patients treated with ampicillin were also studied. The incidences of diarrhoea in both groups were similar (11% in the lincomycin-clindamycin group and 8% in the ampicillin group). One patient developed pseudomembranous colitis associated with two prolonged courses of lincomycin therapy. The results suggest that the risks associated with the use of lincomycin are acceptable if the drug is given for the approved specific indications.

Adult↗

PubMed1988

Effects of lincomycin on synthesis of TEM beta-lactamase by Escherichia coli.

Sub-inhibitory concentrations of lincomycin slightly inhibit growth of Escherichia coli carrying plasmid RP4 and cause a 2-fold increase in TEM-2 beta-lactamase. To analyze this effect, cultures were pulse-labeled with [3H]leucine, chased with non-radioactive leucine and immunoprecipitated with anti-beta-lactamase antiserum. The synthesis rate of beta-lactamase was two times higher in inhibited cultures than in control cultures. No significant decrease of labeled enzyme occurred during the 30 minutes chase, indicating no degradation of beta-lactamase. The rate of maturation of pre-beta-lactamase was determined by measuring the decrease in the amount of pre-beta-lactamase after a 1-minute labeling interval. There was no significant difference between the control and lincomycin-treated cultures, indicating that posttranslational translocation is not involved in the stimulation. Both plasmid encoded and chromosomally encoded TEM-1 beta-lactamase increased in the presence of lincomycin. The effects of other protein synthesis inhibitors on the synthesis of TEM-1 beta-lactamase were examined. The stimulation of beta-lactamase synthesis by lincomycin appears to be specific for macrolide and related antibiotics and is not a general phenomenon resulting from partial inhibition of protein synthesis.

Anti-Bacterial Agents↗