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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↗

PubMed1991

A pilot study of parenteral lincomycin therapy in soft tissue infections.

From our study it is clear that lincomycin, given 300 mg intra muscularly daily in a single dose, is effective in a wide range of soft tissue infections especially those involving the head and neck region. An overall success rate of 88.8 per cent was observed in the 150 patients selected for the study. It is significant that in none of the subjects was any untoward reaction observed or reported. Hitherto all the previous systematic surveys on lincomycin appear to have been carried out on bone infections where, undoubtedly, lincomycin is highly effective. This pilot study furnishes an encouraging report on the successful treatment of soft tissue infections with parenteral lincomycin.

Adolescent↗

PubMed1989

Comparative antimicrobial activities of ribostamycin, gentamicin, ampicillin and lincomycin in vitro and in vivo.

The antimicrobial activity of ribostamycin, a unique aminoglycoside antibiotic possessing a neutral sugar component, was compared with those of gentamicin, ampicillin and lincomycin in vitro and in vivo. Ribostamycin showed comparable or slightly weaker in vitro activity than the reference antibiotics against Gram-positive bacteria. Against Gram-negative bacteria, ribostamycin was less active than gentamicin, but comparable to or more active than ampicillin. Lincomycin was less active or inactive to Gram-negative bacteria. Ribostamycin was active against some gentamicin-resistant bacteria, especially K. pneumoniae possessing the aminoglycoside-modifying enzymes AAC(3)-l and AAD(2"). The in vivo activity of ribostamycin was weaker than that of gentamicin, but comparable to that of ampicillin and lincomycin against Gram-positive bacteria, and superior to that of ampicillin against Gram-negative bacteria. The in vivo activity of ribostamycin was characterized by (i) and ED50 value not so affected by the challenge inoculum as that of ampicillin; (ii) a lower ED50 value by bolus administration than that by divided administration of the same dosage; and (iii) a lower ED50 value than that expected from the MIC value as compared with that of ampicillin and lincomycin. These characteristics are explained by the rapid and potent bactericidal activity of ribostamycin at high inoculum and high drug concentration, assisted by high serum concentration in mice.

Ampicillin↗

PubMed1988

[Effect of lincomycin and staphylococcal vaccine on the course of experimental staphylococcal sepsis].

Therapeutic efficacy of lincomycin used alone and in combination with inactivated staphylococcal vaccine and the effect of these agents on synthesis of antibodies and their content in blood serum were investigated. Lincomycin was shown to inhibit septic processes in the host. After its administration the number of the pathogens in the blood and organs markedly decreased. At the same time, lincomycin lowered antibody synthesis in the lymphoid organs and the content of alpha-antitoxins in blood serum. The use of lincomycin in combination with inactivated staphylococcal vaccine promoted an increase in the number of the antibody forming cells in the spleen and lymph nodes and the content of the antibodies to the staphylococcal alpha-toxin in blood serum of the animals with staphylococcal sepsis.

Animals↗

PubMed1988

[Intramolecular hydrogen bonds and conformation of the lincomycin molecule in organic solvents].

IR spectra (1600-1800 and 3000-3650 cm-1) of lincomycin base solutions in inert (CCl4 and C2Cl4), proton acceptor (dioxane, dimethylsulfoxide and triethyl amine) and proton donor (CHCl3, CD3OD and D2O) solvents were studied. Analysis of the concentration and temperature changes in the spectra revealed that association in lincomycin in the inert solvents was due to intramolecular hydrogen linkage involving amide and hydroxyl groups. Disintegration of the associates after the solution dilution and temperature rise was accompanied by formation of intramolecular bonds stabilizing the stable conformation structure of the lincomycin molecule. The following hydrogen linkage in the conformation was realized: NH...N (band v NH...N at 3340 cm-1), OH...O involving the hydroxyl at C-7 and O atoms in the D-galactose ring (band v OH...O at 3548 cm-1), a chain of the hydrogen bonds OH...OH...OH in the lincomycin carbohydrate moiety (band v OH...O at 3593 cm-1 and v OH of the end hydroxyl group at 3625 cm-1). Bonds NH and C-O of the amide group were located in transconformation. Group C-O did not participate in the intramolecular hydrogen linkage.

Hydrogen Bonding↗

PubMed1978

[Results of 10 years of use of lincomycin (1966-1976) in the clinics of the N. N. Priorov Central Research Institute of Traumatology and Orthopedics].

During 10 years 1063 patients were treated with lincomycin used parentally or orally at the N. N. Priorov Central Research Institute of Traumatology and Orthopedy. The doses and the rate of its use depended on the state of the patient, its age and weight. Lincomycin was used for the treatment of patients with osteomyelitis or purulent wound infection, as well as for prophylaxis of suppuration. The drug was used for a long period of time under conditions of the same hospital, and it was shown that it remained up to the present days highly effective in therapy of infections and especially bone infections caused by staphylococci sensitive to it. The 10-year study of staphylococcal sensitivity to lincomycin revealed an insignificant increase in the development of resistance to it. The paper presents data on the importance of adequate surgical interventions in addition to the antibiotic therapy in cases with bone infections. A possibility of lincomycin combined use with other antibiotics and gentamicin or kanamycin in particular was shown. Complications, such as diarrhea and urticaria were registered in 11 patients.

Adult↗

PubMed1978

Therapeutic effects of various concentrations of lincomycin in drinking water on experimentally transmitted swine dysentery.

Three experimental studies were conducted in 232 growing pigs (8 to 12 weeks old) to evaluate the therapeutic effects of various concentrations of lincomycin in drinking water, against swine dysentery experimentally transmitted, by oral inoculation or by contact-commingling exposure. Four or 5 concentrations of lincomycin were used in each experiment (132, 66, 33, 16.5 or 0.0 mg/L of drinking water). Medication was initiated 7 to days after exposure and was continued for 6 to 10 days. Both methods of exposure were capable of transmitting the disease successfully. A more marked dose response was noticed in pigs inoculated orally than in pigs that were exposed by contact. All concentrations of lincomycin were effective for the treatment of swine dysentery by oral or by contact exposure. At the smaller concentration of 16.5 mg/L of drinking water, lincomycin was less effective for treating the disease than it was at greater concentrations. The suggested optimal concentration was 33 mg of lincomycin/L of drinking water for the treatment of swine dysentery.

Administration, Oral↗

PubMed1977

[Lincomycin concentration in human serum and pulmonary tissue].

Lincomycin levels in the blood serum and lung tissue were determined in 17 patients after surgical operations because of the lung diseases, the drug being administered in a dose of 500 mg. In 45 to 330 minutes after administration of the antibiotic its concentration in the blood serum and lung tissue was 4.6 +/- 10 lambda/ml(average 7.7 lambda/ml) and 1.4-8 lambda/gm (average 4.4 lambda/gm) respectively. The lincomycin level in the lung tissue amounted to 61 per cent of that in the blood setum. The concentration of lincomycin the lung tissue was several times higher than the minimum level necessary for inhibition of the strains included in the antibiotic antibacterial spectrum. Therefore, lincomycin is an important drug in the treatment of infections of the respiratory tract.

Adult↗

PubMed1979

Intraocular penetration of topically applied lincomycin hydrochloride in rabbits.

Ocular penetration of lincomycin hydrochloride in albino rabbits was determined by bioassay. On topical application, the frequency of multiple instillation of drops played an important role in producing therapeutic levels in the anterior chambers. Therapeutic levels were attained in the cornea, aqueous humor, and iris-ciliary body, with peak values occurring at 30 to 45 minutes. Varying the pH of the dosing solution did not change ocular absorption and distribution substantially. Removal of corneal epithelium, however, greatly enhanced absorption. Relative to clindamycin, lincomycin hydrochloride had longer onset of peak values and lower overall concentration in ocular tissues. Intravitreous injection of lincomycin hydrochloride produced therapeutic and steady levels of antibiotic in anterior chambers. Injection produced a concentration in aqueous humor twice that achievable topically. The major route of elimination from the posterior chamber was through retina-choroid.

Administration, Topical↗

PubMed1974

Genetics of resistance to macrolide antibiotics and lincomycin in natural isolates of Streptococcus pyogenes.

Of 5 clinically isolated strains of Streptococcus pyogenes, 3 showed high-level resistance to erythromycin and lincomycin that was inducible by subinhibitory concentrations of these drugs (IR strains) while 2 strains exhibited constitutive erythromycin and lincomycin resistance (CR strains) which was expressed without prior exposure to low drug concentrations. The CR strain 15346 showed spontaneous loss of resistance whereas resistance in the other strains was quite stable even under curing conditions. The IR strain 13234 was found to be polylysogenic for at least 4 different phages designated P13234ma, mi, mu, and mo. Phage mo, antigenically distinct from the other three, was shown to mediate the transfer of the resistance determinant ERL1 of strain 13234. ERL1 if borne by appropriate strains was also transducible by the virulent phage A25. ERL1 behaved as a discrete genetic unit in transduction experiments, was not linked to either of two chromosomal regions governing resistance to antibiotics that affect the ribosome, could be transferred to recombination deficient hosts, represented a relatively large UV inactivation target, and showed no stimulation of transduction by low UV doses. These findings suggest that resistance to erythromycin and lincomycin in certain natural isolates of S. pyogenes is specified by, or under the control of, a plasmid.

Bacteriophages↗

PubMed1979

Analysis of lincomycin resistance mutations in Escherichia coli.

High level lincomycin resistant strains of Escherichia coli were isolated and screened for altered ribosomal proteins and functions. Amongst 58 strains investigated by electrophoresis one had an altered ribosomal protein S7, another one a mutated L14 and two showed altered L15 proteins. A correlation between these alterations and lincomycin resistant growth could not be demonstrated by genetic analysis for any of the mutants. In vitro, however, extracts from the two L15 mutants were less sensitive to inhibition by the drug. A gene locus (linR) responsible for the lincomycin resistance phenotype was mapped at min 30 of the Escherichia coli chromosome near tyrR; it seems to be identical to the previously described linB locus (Apirion, 1967); however, in contrast to these reports it does not seem to alter any ribosomal function.

Bacterial Proteins↗

PubMed1975

Pharmacokinetics of lincomycin and clindamycin phosphate in a canine model.

Linomycin and clindamycin phosphate were studed in a canine model in which acute biliary obstruction was produced during iv infusion of antibiotic. Hepatic and renal extraction, bilary and renal excretion, and concentrations in liver and kidney were measured. Total and nonesterified clindamycin were assayed. The antibiotics were taken up by the liver at similar rates; however; the rates of excretion and concentration in bile were significantly higher for lincomycin than for clindamycin. Biliary obstruction did not affect the concentration of either antibiotic in canalicular bile. Lincomycin was extracted by the kidneys and excreted into urine at a much higher rate than was clindamycin. Concentrations of nonesterified clindamycin in the hepatic vein were higher than those in the portal vein, an observation suggesting metabolic activation within the liver. This relation was reversed by bilary obstructon. The results in this canine model indicate a greater role for the kedney in the disposition of lincomycin than in that of clindamycin, major differences between the rates of biliary excretion of the two agents, and a probable change in the metabolism of clindamycin procued by acute bilary obstruction.

Animals↗

PubMed1976

Susceptibility of "enterobacteria" to penicillins, cephalosporins, lincomycins, erythromycin, and rifampin.

Agar dilution tests for susceptibility of gram-negative rods and enterococci were done with a number of penicillins, cephalosporins, lincomycin analogues, erythromycin, and rifampin. Many in the first three categories were investigational drugs. All were generally less active than aminoglycoside and tetracycline antibiotics against gram-negative rods and more active against enterococci. Cephalosporins as a group were more active than penicillins against Klebsiella pneumoniae and Escherichia coli and less active enterococci. Both groups were equally active against Enterobacter, Proteus, and Providencia but inactive against most strains of Serratia and all strains of Pseudomonas; however, ticarcillin, carbenicillin, and BL-1654 were active against most strains of Pseudomonas. Penicillins and cephalosporins were more active against Proteus mirabilis than against indole-positive Proteus. Lincomycins had little or no activity against gram-negative rods but were moderately active against enterococci. Erythromycin was more active than the lincomycins, but rifampin was much more active than either of these types of drug. Of the penicillins, ticarcillin, carbenicillin, and BL-P1654 were the most active against gram-negative rods, whereas BL-P1654, amoxicillin, and ampicillin were the most active against enterococci. The penicillinase-resistant penicillins, cyclacillin, and penicillin V were essentially inactive against gram-negative rods. Of the cephalosporins tested, cephanone and cefamandole were the most active against most gram-negative rods, whereas cephaloridine and cephacetrile were the most active against enterococci. The least active of the cephalosporins against most species were cephradine, cephalexin, and cephapirin, but cefoxitin was the least active against enterococci.

Acinetobacter↗

PubMed1992

Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli 23S ribosomal RNA.

Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli ribosomes has been compared by chemical footprinting. The protection afforded by both drugs is limited to the peptidyl transferase loop of 23S rRNA. Under conditions of stoichiometric binding at 1 mM drug concentration in vitro, both drugs strongly protect 23S rRNA bases A2058 and A2451 from dimethyl sulphate and G2505 from kethoxal modification; G2061 is also weakly protected from kethoxal. The modification patterns differ in that A2059 is additionally protected by clindamycin but not by lincomycin. The affinity of the two drugs for the ribosome, estimated by footprinting, is approximately the same, giving Kdiss values of 5 microM for lincomycin and 8 microM for clindamycin. The results show that in vitro the drugs are equally potent in blocking their ribosomal target site. Their inhibitory effects on peptide bond formation could, however, be subtly different.

Base Sequence↗

PubMed1976

Antibiotic susceptibilities of streptococci from the mouth and blood of patients treated with penicillin or lincomycin and clindamycin.

Patients undergoing dental extractions were non-randomly allocated to three groups, one of which received no antibiotic, one benzylpenicillin followed by oral penicillin for 5 days, and the third intramuscular lincomycin followed by oral clindamycin. Dental extraction was performed at the beginning of the course of chemotherapy. Streptococci were isolated from the extracted teeth, from blood cultures collected before and immediately after dental extraction, and from sutures removed from the gums 5-7 days after the operation. The species of these organisms was determined, and their susceptibilities to penicillin, clindamycin, cephaloridine, erythromycin and tetracycline were assessed. The majority of streptococci isolated from teeth belonged to the species Streptococcus sanguis, S. mitior, S. mutans and S. milleri. Occasional isolates of each of these organisms collected before the antibiotic could take effect were resistant to penicillin. Three of these species, but not S. mutans, were the commonest streptococci to be isolated from the blood after dental extraction. Penicillin completely suppressed dental bacteriaemia under the conditions of our investigation, and lincomycin reduced the incidence by about 60 per cent. The commonest streptococci from sutures were also S. sanguis, S. mitior, S. mutans and S. milleri. S. faecalis was also isolated, but only in patients who had received antibiotics. Among the non-faecalis organisms, penicillin resistance was significantly more frequent among isolates from patients given penicillin than from patients not given this antibiotic, and clindamycin resistance was significantly more frequent among isolates from patients given lincomycin and clindamycin than from patients not given these antibiotics.

Anti-Bacterial Agents↗

PubMed1977

The mechanism of lincomycin-induced diarrhoea.

Metabolic studies were performed before and seven days after treating rats orally with lincomycin. Following the treatment the mean faecal weight increased from 302.2 g/72 hr +/- 3.8 (S.D.) to 65.5 +/- 8.2. The faecal fat excretion was unchanged, and the weight increase was mainly due to increased water content. To find whether the watery diarrhoea was due to bile acid malabsorption, the absorption rate of [14C]-taurocholic acid was measured in untreated rats and rats treated with lincomycin using an in vivo perfusion technique. There was no significant difference in bile acid absorption rate measured at three different concentrations of bile acid in the perfusate. Alternative mechanisms of lincomycin-associated diarrhoea are discussed.

Animals↗

PubMed1992

Molecular cloning and characterization of two lincomycin-resistance genes, lmrA and lmrB, from Streptomyces lincolnensis 78-11.

Two different lincomycin-resistance determinants (lmrA and lmrB) from Streptomyces lincolnensis 78-11 were cloned in Streptomyces lividans 66 TK23. The gene lmrA was localized on a 2.16 kb fragment, the determined nucleotide sequence of which encoded a single open reading frame 1446 bp long. Analysis of the deduced amino acid sequence suggested the presence of 12 membrane-spanning domains and showed significant similarities to the methylenomycin-resistance protein (Mmr) from Streptomyces coelicolor, the QacA protein from Staphylococcus aureus, and several tetracycline-resistance proteins from both Gram-positive and Gram-negative bacteria, as well as to some sugar-transport proteins from Escherichia coli. The lmrB gene was actively expressed from a 2.7 kb fragment. An open reading frame of 837 bp could be localized which encoded a protein that was significantly similar to 23S rRNA adenine(2058)-N-methyltransferases conferring macrolide-lincosamide-streptogramin resistance. LmrB also had putative rRNA methyltransferase activity since lincomycin resistance of ribosomes was induced in lmrB-containing strains. Surprisingly, both enzymes, LmrA and LmrB, had a substrate specificity restricted to lincomycin and did not cause resistance to other lincosamides such as celesticetin and clindamycin, or to macrolides.

Amino Acid Sequence↗

PubMed1975

Lincomycin in selective medium for the isolation of Neisseria gonorrhoeae.

For the isolation of gonococci, the selective culture medium containing colistin, vancomycin, nystatin and trimethoprim which is usually employed has been changed by substituting lincomycin for vancomycin. The best result was obtained if a concentration of 1/2 mug lincomycin/ml medium was used. This is a concentration of lincomycin considerably lower than that which by other investigators is considered most suitable for the purpose. However, the culture medium used by the latter did not contain trimethoprim. The use of 1/2 mug lincomycin/ml instead of vancomycin 3 mug/ml in the medium caused a slightly more pronounced growth of unwanted organisms. In spite of this, the results obtained by the medium containing lincomycin showed that the number of samples positive for gonococci was 7 per cent higher, and that the number of patients with gonococcal infections to be discovered was 4 per cent higher than the numbers obtained by the medium containing vancomycin. The results were considered highly favourable and, accordingly, by now our laboratory uses 1/2 mug lincomycin/ml medium in the routine isolation of gonococci.

Culture Media↗