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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↗
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↗
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↗
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↗
PubMed1983

Lincomycin dose response for treatment of necrotic enteritis in broilers.

A dose response study was conducted to determine the appropriate (optimal) lincomycin concentration in drinking water for the treatment of necrotic enteritis (NE) in broilers. The study was replicated twice over time using a total of 2,895 broilers. Birds were raised in a facility containing a built-up litter from a source that experienced NE. They were commingled from 1 day of age until NE was observed. Lincomycin was mixed in drinking water at a rate of 0, .528, 2.114, 8.454, or 33.818 mg/liter for a period of 7 days. The study was terminated 3 weeks after initiation of therapy. Necrotic enteritis was diagnosed by mortality and pathological findings. The data on mortality were analyzed statistically using analysis of variance procedures. The Walker-Carmer technique was applied to estimate the appropriate lincomycin concentration. Lincomycin was effective for the treatment of NE in broilers at concentrations of greater than or equal to 2.114 mg/liter of drinking water. The minimal effective dose that would achieve maximal treatment response (optimal dose) against NE in broilers was estimated to be 16.9 mg lincomycin/liter of drinking water.

Animals↗
PubMed1983

Therapeutic effect of optimal lincomycin concentration in drinking water on necrotic enteritis in broilers.

The efficacy of 16.9 mg lincomycin/liter of drinking water was evaluated for the treatment of necrotic enteritis (NE) in 743 broiler-type chickens. Birds were raised in a facility containing a built-up litter obtained from a source that experienced NE. They were commingled from 1 day of age until NE was observed. Two groups of 6 pens each were given 0 or 16.9 mg lincomycin/liter of drinking water. Water medication was offered fresh daily for 7 days and the study was terminated 3 weeks after initiation of therapy. The susceptibility of Clostridium perfringens to lincomycin was determined in vitro. The test organism was susceptible to lincomycin as reflected by minimal inhibitory concentration and minimal lethal concentration of .156 microgram/ml. Mortality attributed to NE was 0% in lincomycin treated birds and 14% in nonmedicated control birds (P less than .01). Lincomycin water medication was highly effective for the treatment of NE in broilers.

Animals↗
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↗