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Kinetics of binding of macrolides, lincosamides, and synergimycins to ribosomes.

The synergistic effect of type A (virginiamycin M (VM)) and type B (virginiamycin S (VS)) synergimycins and their antagonistic effect against erythromycin (a 14-membered macrolide) for binding to the large ribosomal subunit (50 S) have been related. This investigation has now been extended to 16-membered macrolides (leucomycin A3 and spiramycin) and to lincosamides (lincomycin). A dissociation of VS-ribosome complexes was induced as well by 16-membered macrolides as by lincosamides. The observed dissociation rate constant of VS-ribosome complexes was identified with the kappa-vs in the case of 16-membered macrolides, but linearly related to lincomycin concentration, suggesting a direct binding of the latter antibiotic to VS-ribosome complexes and the triggering of a conformational change of particles entailing VS release. Two different mechanisms were also involved in the VM-promoted reassociation to ribosomes of VS previously displaced by either macrolides or lincosamides. By binding to lincosamide-ribosome complexes, VM induced a conformational change of ribosomes resulting in higher affinity for VS and lower affinity for lincosamides. On the contrary, an incompatibility for a simultaneous binding of VM and 16-membered macrolides to ribosomes was observed. These results have been interpreted by postulating specific (nonoverlapping) and aspecific (overlapping) antibiotic binding sites at the peptidyltransferase domain. All the kinetic constants of five antibiotic families (type A and B synergimycins, 14- and 16-membered macrolides, and lincosamides) and a topological model of peptidyltransferase are presently available.

Erythromycin↗

Pneumococci resistant to erythromycin.

Susceptibility to erythromycin was determined for all pneumococci isolated in one laboratory from clinical specimens between 1969 and 1977. All 4724 isolates examined prior to October 1973 were susceptible to erythromycin. From October 1973 to December 1977, 64 (0.71%) of 8995 pneumococcus isolates were resistant to erythromycin. The resistant strains were isolated from 38 patients living in six widely separated communities in Alberta. The erythromycin-resistant strains were of nine capsular types, including six that often cause bacteremic disease and five for which resistance to erythromycin has not been reported hitherto. Certain strains of type 33 and of type 15 were highly resistant, the minimum inhibitory concentration (MIC) of erythromycin being 2000 microgram/mL; these strains were also highly resistant to lincomycin and clindamycin. Resistance in strains of other types was much lower, the MIC of erythromycin being 0.6 to 20 microgram/mL, and all but one of these strains were susceptible to lincomycin and clindamycin. All the erythromycin-resistant pneumococci were suspectible to penicillin.

Adolescent↗

The effect of adsorbant and anti-inflammatory drugs on secretion in ligated segments of pig intestine infected with Escherichia coli.

Four adsorbant drug preparations, Kaopectate, colloidal Attapulgite, noncolloidal Attapulgite and Pepto-bismol were investigated for their effects on fluid accumulation in ligated segments of pig intestine inoculated with enteropathogenic Escherichia coli. Two anti-inflammatory drugs. aspirin and methylprednisolone, and two antibiotics, lincomycin and polymyxin B, were also tested. All the drugs except the two anti-inflammatory products were given by injection into the lumen of the intestine. Aspirin was given orally and methylprednisolone was given intramuscularly. The antibiotics were tested at levels at which they had no significant antibacterial effect in in vitro tests. The adsorbant drugs colloidal Attapulgite and Pepto-bismol were shown to be effective in reducing fluid accumulation in ligated segments of pig intestine infected with enteropathogenic E. coli. In the case of Peptobismol this effect was associated with an antibacterial effect as well as an antitoxic effect, probably due to its adsorbant properties. It is possible that an aspirin-like effect in the gut due to the active ingredient bismuth subsalicylate may have contributed to the effectiveness of Pepto-bismol. Colloidal Attapulgite was demonstrated to have an antitoxic effect but did not have an antibacterial effect. In high doses, the anti-inflammatory drugs acetylsalicylic acid and methylprednisolone were marginally effective in reduction of fluid accumulation in the same test system. Lincomycin was shown to reduce intestinal fluid secretion, whereas polymyxin B had no effect.

Animals↗

Aetiologic agents of septic sore throat in Thai children.

A bacteriological study of children with respiratory infections in Bangkok during January to November 1976 revealed that 37% of the patients had symptoms and sign of bacterial pharyngotonsillitis. Twenty-six per cent of these children harboured Streptococcus pyogenes in their throats. The numbers of streptococci other than group A and Staphylococcus aureus were increased in the children with respiratory infections. However, Staph. aureus was found as the sole organism in children with exudate more often than in the children with only URI. The possible role of Staph. aureus in bacterial pharyngitis should not be ignored. Penicillin remains a drug of choice for the treatment of streptococcal pharyngitis. If penicillin is contraindicated, erythromycin should be preferred over lincomycin as a second choice of drug in order to avoid treatment failure if lincomycin resistant streptococci are present.

Adolescent↗

[Plasmid-determined streptococcal resistance to antibiotics].

The analysis of the genetic organization of the determinant ERLI by means of obtaining and studying the antibiotic sensitive mutants from the strain resistant to erythromycin and lincomycin provided experiment data in favour of the fact that inducable resistance to erythromycin and lincomycin determined by the plasmid might be defined by the same or closely linked genes.

Anti-Bacterial Agents↗

Superinfections of the lung. An evaluation by serial transtracheal aspirations.

A prospective evaluation of cephaloridine, cephalothin, and lincomycin was conducted in 85 patients with pneumonia. None of the 50 with previous history of allergic sensitivity to penicillin had an allergic reaction. All cases of pure "pneumococcal pneumonia" were cured, regardless of the drug. Eight patients with polymicrobial pneumonia were cured by the cephalosporins, while lincomycin was ineffective in four patients who had polymicrobial pneumonia. Although expectorated sputum and exudates from the nasopharyngeal and oropharyngeal areas contained large concentrations of Staphylococcus aureus and various Gram-negative bacillary species during and at the end of therapy, serial cultures of transtracheal aspirate and the clinical course failed to confirm "superinfection" of the lung.

Adult↗

[Treatment and prevention of experimental pneumonias, caused by L forms of bacteria].

On a model of experimental pneumonia in mice caused by the L-forms of bacteria against the background of diminished immunity a study was made of the therapeutic efficacy of penicillin, lincomycin, lysozyme and gamma-globulin. Lincomycin, particularly in combination with biologically-active preparations, proved to be expedience for the treatment and prophylaxis of pneumonia caused by the mentioned bacteria; a rapid arrest of pneumonic process occurred and more animals survived. In the greater percentage of cases the use of penicillin was accompanied by generalization of the process.

Animals↗

Evaluation of a selective medium for isolation of Haemophilus pleuropneumoniae.

Crystal violet, lincomycin, spectinomycin and bacitracin were evaluated as selective agents in media for isolation of Haemophilus pleuropneumoniae. No single antimicrobial agent or combination of two or more inhibited all non-Haemophilus strains (Escherichia coli, Pasteurella haemolytica, Pasteurella multocida, Streptococcus faecalis, Streptococcus equisimilis and Staphylococcus aureus) without marked suppression of 16 H. pleuropneumoniae strains. A medium containing 1 micrograms/mL of crystal violet, 1 microgram/mL of lincomycin, 8 micrograms/mL of spectinomycin and 128 micrograms/mL of bacitracin inhibited one E. coli strain and the Gram-positive strains while H. pleuropneumoniae strains were suppressed to a minor degree only. Haemophilus pleuropneumoniae was isolated on the selective medium on three occasions from the nose or pharynx of two out of eight experimentally inoculated pigs. Haemophilus pleuropneumoniae was recovered from the nose of only two pigs at necropsy and from tonsil of one, whereas the lower airways in most pigs and the lung lesions in all pigs were positive. There was no advantage to using the selective medium for the recovery of H. pleuropneumoniae at necropsy from these eight experimentally infected pigs, probably because other bacteria were absent or present in very low numbers in the tissues with H. pleuropneumoniae. The isolation rate on selective medium was higher than the rate on non-selective medium (p less than or equal to 0.1; chi 2 test) when the airways of slaughtered pigs were cultured. This was likely due to a high degree of contamination. Dry swabs placed in tryptone yeast extract with nicotinamide-adenine-dinucleotide gave a significantly higher recovery rate than commercial Culturette swabs in modified Stuart's transport medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Agar↗

The effect of antibiotics against bovine mycoplasmas and ureaplasmas.

A combination of lincomycin-spectinomycin-tylosin was tested against several strains of mycoplasmas and acholeplasmas as might be encountered in bovine semen and shown to be effective against them. This combination as well as minocin , rosaramicin, rosoxacin, tiamulin, gentamicin and declomycin were tested in vitro against 58 isolates of ureaplasma from the bovine urogenital tract. The lincomycin-spectinomycin-tylosin combination, minocin , rosaramicin, tiamulin and declomycin were quite active, while rosoxacin and gentamicin were much less active against the test strains.

Acholeplasma laidlawii↗

Sensitivity of staphylococci from farm animals to antibacterial agents used for growth promotion and therapy. A ten year study.

The following results were obtained during the period of 1970 to 1979-1980 in a study of 1040 Staphylococcus aureus strains in Belgium from cattle, poultry and pigs and 138 Staphylococcus hyicus strains from pigs, using the agar dilution technique and different penicillinase test methods: -- The incidence of penicillinase-positive strains increased in bovine and porcine S. aureus strains but decreased in poultry strains. From 1974 on more than 75% of S. aureus strains from cow udders produced penicillinase. -- The numbers of tetracycline-resistant strains steadily decreased during the period under investigation. -- Strains resistant to the macrolides and lincomycin were most frequent among S. hyicus and S. aureus strains from pigs isolated in 1973-1975. They were less numerous in 1979-1980. The inducible type of macrolide-resistance was found only among strains from poultry and cattle. In 1979-1980 strains resistant to lincomycin but susceptible to macrolide-antibiotics were detected. -- Two types of sensitivity to bacitracin were discovered: highly sensitive strains were frequent in cattle and rare in poultry. Intermediately sensitive strains dominated in poultry and pigs. These two groups of strains belonged to distinct chemotypes. Only one poultry strain was highly resistant to bacitracin. -- Number of neomycin-, sulphonamide- and chloramphenicol-resistant strains and strains resistant to the penicillinase-stable penicillins and cephalosporins were low and did not increase. -- Novobiocin resistance was only found among strains from broiler breeders and broilers. -- All strains tested were sensitive to the nitrofurans and related compounds (furazolidone, nitrovin), flavomycin, carbadox, trimethoprim, rifamycin and the virginiamycin combination.

Animals↗

Pseudomembranous colitis: isolation of two species of cytotoxic clostridia and successful treatment with vancomycin.

Lincomycin-resistant Clostridium sporogenes obtained from the stools of a patient with lincomycin-associated pseudomembranous colitis produced a heat-stable cytotoxin in low titre when grown in chopped meat medium. Vancomycin eradicated this strain and all other clostridia, and controlled the symptoms. When diarrhea recurred 7 days after treatment with vancomycin was stopped, clostridia including C. sporogenes and C. difficile were again isolated. The C. difficile produced a heat-labile cytotoxin in high titre that was unaffected by growth in various media and induced colitis in hamsters. Treatment with vancomycin, to which all the clostridia were sensitive, eradicated both toxic species and controlled the diarrhea. Antibiotic-induced pseudomembranous colitis may be associated with more than one species of toxin-producing clostridia. Vancomycin therapy should be continued for 10 days or more in patients with severe disease to eradicate the responsible organism.

Aged↗

Determination of MICs for staphylococci using the API ATB quinolone and API ATB macrolide systems.

The determination of minimal inhibitory concentrations (MICs) is cumbersome, but remains necessary in certain cases. We tested the two ATB MIC experimental strips (Biomérieux SA), of which each contains 4 antimicrobials of the same class. These strips can be read automatically. The MIC quinolone strip contains nalidixic acid, pefloxacin, ofloxacin and ciprofloxacin, whereas the MIC macrolide (lincosamide-streptogramin) strip contains erythromycin, clindamycin, lincomycin, and pristinamycin. In order to evaluate these strips, 102 S. aureus and 63 coagulase negative staphylococci were used. Correlation coefficients for these MICs (micrograms/ml) and disk diffusion inhibition zone diameters (mm) were nalidixic acid -0.59, pefloxacin -0.95, ofloxacin -0.95, ciprofloxacin -0.91, erythromycin -0.98, clindamycin -0.96, lincomycin -0.96, and pristinamycin -0.64. Using the Biomic system (Giles Scientific USA), the same zone diameters were converted to MICs (micrograms/ml). Rates of agreement (+/- 1 dilution) between ATB MICs and Biomic MICs were nalidixic acid 96 p. cent, ciprofloxacin 98 p. cent, erythromycin 99 p. cent and clindamycin 98 p. cent. Rates of agreement between MICs for the same strains determined using agar dilution and ATB MICs were nalidixic acid 93 p. cent, pefloxacin 100 p. cent, ciprofloxacin 99 p. cent, ofloxacin 94 p. cent and erythromycin 96 p. cent. The ATB MIC strips are an easy-to-use tool for MIC determination and their composition is well-suited to the study of phenotypic resistance and detection of low-level resistance.

Ciprofloxacin↗

Clindamycin-associated colitis in hamsters: protection with vancomycin.

Clindamycin and lincomycin produced a lethal enterocolitis in 65 of 67 Syrian hamsters. The administration of oral or parenteral vancomycin to recipients of clindamycin or lincomycin was uniformly protective in 49 patients. These results suggest that certain bacteria play a role in the pathogenesis of enterocolitis in this model.

Animals↗

Changes in macrophage function during chemotherapy.

Antibiotics, in addition to killing or inhibiting the growth of microorganisms, may also affect the mechanism of host defence in many ways. Such effects may be clinically relevant especially in the case where an impairment of immunological function can be seen. We, therefore, decided to study the influence of penicillin G, cefotaxim, ceftazidime, streptomycin, and lincomycin on the function of phagocytes by using the macrophage adherence assay and the macrophage spreading assay. We also followed the concentrations of neopterin and interferon gamma (IFN gamma) in the plasma of mice treated with the above mentioned antibiotics. Changes in adherence of peritoneal macrophages were seen in mice treated with therapeutic doses of penicillin G and cefotaxim, after 2 h of incubation. Cefotaxim and streptomycin in the usual therapeutic dose and ceftazidime in a fourfold higher dose influenced the capacity of peritoneal macrophages to spread on a glass surface. The same was seen with lincomycin when administered in the therapeutic dose and in a fourfold higher dose. In all the mice treated with antibiotics the concentration of IFN gamma was higher than in the control mice, while the reverse was seen concerning neopterin release, with an exception in mice treated with streptomycin.

Animals↗

Antimicrobial susceptibility of Fusobacterium necrophorum isolated from bovine hepatic abscesses.

OBJECTIVE: To determine the resistance and susceptibility to antimicrobial compounds of Fusobacterium necrophorum isolates from bovine hepatic abscesses. PROCEDURE: 37 isolates of F necrophorum (21 subsp necrophorum and 16 subsp funduliforme) isolated from bovine hepatic abscesses were obtained from cultures grown and maintained in anaerobic brain heart infusion broth. A broth dilution method was used as an initial screening to determine general susceptibility to 31 antimicrobial compounds. The minimal inhibitory concentrations (MIC) of 19 of the antimicrobial compounds that inhibited growth in the initial test were determined by use of the broth microdilution method. RESULTS: Fusobacterium necrophorum isolates were generally susceptible to penicillins, tetracyclines (chlortetracycline and oxytetracycline), lincosamides (clindamycin and lincomycin), and macrolides (tylosin and erythromycin), and were resistant to aminoglycosides (kanamycin, neomycin, gentamicin, and streptomycin), ionophores (except narasin), and peptides (avoparcin, polymyxin, and thiopeptin). The 5 antimicrobials (bacitracin, chlortetracycline, oxytetracycline, tylosin, and virginiamycin) that have FDA approval for prevention of liver abscesses in feedlot cattle were inhibitory to F necrophorum. Differences in antimicrobial susceptibility patterns were observed between the 2 subspecies only for clindamycin and lincomycin. The MIC of F necrophorum isolates from antibiotic-fed cattle were similar to those for isolates from nonantibiotic-fed cattle. CONCLUSIONS: The MIC of FDA-approved antibiotics were not reflective of the efficacy of antibiotics in preventing liver abscesses in feedlot cattle. Also, continuous feeding of tylosin did not appear to select resistant F necrophorum.

Animals↗

Antibiotic-associated colitis.

Among 26,294 hospitalized patients monitored by the Boston Collaborative Drug Surveillance Program (BCDSP), 8,948 (34%) received at least one antibiotic, and none were diagnosed as having drug-induced colitis to in-hospital antibiotic exposure. Seven patients who had taken antibiotics as outpatients, however, were admitted with antibiotic-associated colitis. Six of these patients had taken lincomycin prior to the onset of symptoms; one had taken ampicillin. Six of the patients were hospitalized at a New Zealand hospital and one at a hospital in Canada. The five patients with lincomycin-associated colitis at the New Zealand hospital were admitted over an 11-month period. Severe colitis due to antibiotics has been a rare event in the BCDSP experience, especially in the United States.

Adult↗

Interaction of the yeast pleiotropic drug resistance genes PDR1 and PDR5.

The network of genes which mediates multiple drug resistance in yeast includes, among others, the PDR1 gene, which encodes a putative regulator of gene expression, and PDR5, a locus whose amplification leads to resistance. We demonstrate that disruption of PDR5 causes marked hypersensitivity not only to cycloheximide but also to sulphometuron methyl and the mitochondrial inhibitors chloramphenicol, lincomycin, erythromycin and antimycin. Genetic analysis of double mutants containing an insertion in PDR5 (pdr5:Tn5), which renders cells hypersensitive to cycloheximide, and a pdr1 mutation, which confers resistance to this inhibitor, indicates that the expression of resistance requires a functional PDR5 gene. The same interdependency is observed for chloramphenicol, but not for oligomycin, lincomycin, erythromycin or sulphometuron methyl. Northern analysis of PDR1 and PDR5 transcripts reveals that the 5.2 kbp PDR5 transcript is overexpressed in pdr1 (resistant) mutants, but underexpressed in a disruption of PDR1. These observations provide strong experimental support for our former proposal that the PDR5 gene is a target for regulation by the PDR1 gene product.

Anti-Bacterial Agents↗

Isolation of Mycoplasma bovis from intact and microinjected preimplantation bovine embryos washed or treated with trypsin or antibiotics.

Incubation of day 7 bovine embryos with 10(4) or 10(6) CFU/ml of Mycoplasma bovis (M. bovis) or microinjection of M. bovis into the cells of day 7 embryos did not influence embryonic development. M. bovis was recovered from all embryos washed 10 times by a standard pipetting method or vortexed and pipeted 10 times. M. bovis was also recovered from zonae pellucidae removed and washed from microinjected embryos. Neither treatment with trypsin nor exposure of embryos to combinations of penicillin, streptomycin, lincomycin and spectinomycin, or gentamicin, tylosin, lincomycin, and spectinomycin, inactivated M. bovis.

Animals↗