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PubMed1976

Effect of lincomycin on prevalence, duration, and quantity of Salmonella typhimurium excreted by swine.

Thirty-one swine (7.5 kg live wt) were fed diets which contained 0 or 110 mg of lincomycin/kg. These pigs were then inoculated with a nalidixic acid-resistant strain of Salmonella typhimurium and monitored for 56 days thereafter to determine (1) the quantity of S typhimurium shed in the feces, (2) the length of time the organism was shed, and (3) the number of swine which shed the organism for the 56-day period after exposure. Addition of lincomycin to diets did not alter these 3 criteria from those obtained in S typhimurium-exposed nontreated swine when results for nontreated and treated swine were compared. In addition, the sensitivity of the S typhimurium strain to 8 antibiotics, 1 nitrofuran, and 1 sulfonamide was not affected by in vivo exposure to lincomycin for 39 days. Lincomycin did not produce adverse effects in either inoculated or noninoculated pigs.

Animals↗
PubMed1977

[Pharmacokinetics of lincomycins in experimental staphylococcal sepsis].

Pharmacokinetics of lincomycin hydrochloride and 7-chlor-7-desoxylincomycin hydrochloride (chlolincocin) was studied on albino mice and rabbits with experimental staphylococcal sepsis caused by intravenous introduction of highly pathogenic cultures. The septic process was accompanied by impairement of the kidney function, the pathological changes in the kidneys being most pronounced. The antibiotic levels in the blood and tissues of the internal organs, i.e. liver, kidneys, lungs and spleen increased in the infected animals, while the content of the antibiotic in the urine decreased. Determination of the plasmatic, kidney and extrakidney clearance revealed the increasing role of the extrakidney clearance. The shudy of the concentrations of 7-desoxylincomycin in the bile of the animals subjected to cholecystostomy showed that the role of the liver in elimination of lincomycin increased in the animals with experimental staphylococcal infection. As the state of the animals improved the changes in the pharmacokinetics of lincomycin decreased.

Animals↗
PubMed1996

The rate constant of photoinhibition, measured in lincomycin-treated leaves, is directly proportional to light intensity.

Pumpkin leaves grown under high light (500-700 micromol of photons m-2.s-1) were illuminated under photon flux densities ranging from 6.5 to 1500 micromol.m-2.s-1 in the presence of lincomycin, an inhibitor of chloroplast protein synthesis. The illumination at all light intensities caused photoinhibition, measured as a decrease in the ratio of variable to maximum fluorescence. Loss of photosystem II (PSII) electron transfer activity correlated with the decrease in the fluorescence ratio. The rate constant of photoinhibition, determined from first-order fits, was directly proportional to photon flux density at all light intensities studied. The fluorescence ratio did not decrease if the leaves were illuminated in low light in the absence of lincomycin or incubated in darkness in the presence of lincomycin. The constancy of the quantum yield of photoinhibition under different photon flux densities strongly suggests that photoinhibition in vivo occurs by one dominant mechanism under all light intensities. This mechanism probably is not the acceptor side mechanism characterized in the anaerobic case in vitro. Furthermore, there was an excellent correlation between the loss of PSII activity and the loss of the D1 protein from thylakoid membranes under low light. At low light, photoinhibition occurs so slowly that inactive PSII centers with the D1 protein waiting to be degraded do not accumulate. The kinetic agreement between D1 protein degradation and the inactivation of PSII indicates that the turnover of the D1 protein depends on photoinhibition under both low and high light.

Journal Article↗
PubMed1964

ETHYLATION: BIOLOGICAL FORMATION OF AN S-ETHYL HOMOLOG OF LINCOMYCIN.

Streptomyces umbrinus var. cyaneoniger produces the antibiotic lincomycin. When grown in the presence of ethionine an additional antibiotic is produced. Physical and chemical analyses and incorporation of radioisotopes indicate that the new antibiotic is the S-ethyl homolog of lincomycin.

Amino Acids↗
PubMed1976

Severe pseudomembranous colitis after lincomycin and clindamycin.

Four cases of severe pseudomembranous colitis following the use of lincomycin and clindamycin are described; 2 required emergency total colectomy and 2 died. Cases of such gravity after the use of these drugs have not been previously reported. On hundred and fifty-six orthopaedic cases where clindamycin and lincomycin were used postoperatively are reviewed; 34 had diarrhoea (22 per cent), and 3 of the severe cases occurred in this group. The diagnosis of pseudomembranous colitis may be difficult as the latent period from initiation of drug therapy to commencement of diarrhoea may be as much as 18 days, and that from cessation of drug therapy may be as much as 11 days. The value of early sigmoidoscopy in cases of diarrhoea of obscure aetiology is emphasized, and the characteristic sigmoidoscopic and histological appearances of pseudomembranous colitis are described. As these drugs may produce a lethal condition it is suggested that they should be used with appropriate discretion, especially in the elderly female who appears to be most at risk.

Aged↗
PubMed1986

Protein binding and pharmacokinetics of lincomycin following intravenous administration of high doses.

High-dose infusions of lincomycin 600, 1,200, and 2,400 mg were administered to 14 healthy, adult men. Using model-independent pharmacokinetics, it was found that the half-life, mean residence time, and steady-state volume of distribution of total drug increased with dose, whereas the same parameters remained unchanged for the unbound lincomycin. Although the mean clearance value for total drug increased, this change fell short of being significant at the 5% level and was associated with a decrease in unbound clearance following administration of the 2,400 mg dose. Protein binding studies using ultrafiltration gave direct evidence of saturable serum protein binding and indicated that binding involved at least two distinct classes of binding sites.

Absorption↗
PubMed1979

Anomalous solution behavior of 2-palmitate esters of lincomycin and clindamycin.

The aqueous solubilities of lincomycin and clindamycin 2-palmitate esters are compared. Clindamycin 2-palmitate hydrochloride has an unusually high solubility at 25 degrees, which is due to micelle formation. Both compounds are surface active with relatively low critical micelle concentrations. However, since the Krafft point of lincomycin palmitate is approximately 43 degrees, it does not form micelles below that temperature and appears to be quite insoluble until heated above 43 degrees. The experimental monomeric solubilities of the two compounds agree with calculations based on group contributions to lipophilicity. Clindamycin 2-palmitate hydrochloride solutions are quite sensitive to ions, being salted out as unprotonated base in the form of oily droplets. Salting out correlates well with anionic strength, which is quite constant for the various salts studied. A viscosity maximum occurs with increasing salt addition, with the peaks of the different salts occurring at the same anionic strengths.

Clindamycin↗
PubMed2007

A simple and rapid confirmatory assay for analyzing antibiotic residues of the macrolide class and lincomycin in bovine milk and yoghurt: hot water extraction followed by liquid chromatography/tandem mass spectrometry.

A rapid and simple sample preparation procedure for determining residues of antibiotics of the class of macrolides and lincomycin in whole milk and yoghurt by liquid chromatography/tandem mass spectrometry (LC/MS/MS) is presented. The method is based on the matrix solid-phase dispersion (MSPD) technique with hot water as extractant. After dispersing samples of milk and yoghurt on sand, target compounds were eluted from the MSPD column by passing through it 5 mL of water acidified with 30 mmol/L formic acid and heated at 70 degrees C. After pH adjustment and filtration, a volume of 200 microL of the aqueous extract was directly injected into the LC column. MS data acquisition was generally performed in the multiple reaction monitoring (MRM) mode, selecting two precursor ion to product ion transitions for each target compound. Hot water appeared to be an efficient extracting medium, since absolute recoveries of the analytes in milk and yoghurt were respectively 68-86% and 82-96%. The method proved to be robust as matrix effects, even though present, did not affect significantly the accuracy of the method, as evidenced by analyzing six different batches of both milk and yoghurt. Using roxithromycin (a macrolide antibiotic not used in veterinary medicine) as surrogate internal standard, the accuracy of the method at three different spike levels of the analytes in milk and yoghurt was 86-107% (RSDs not larger than 10%) and 97-117% (RSDs not larger than 13%), respectively. On the basis of a signal-to-noise ratio of 10, we estimated this method can quantify a few ppb of the analytes in milk and yoghurt. These concentrations are well below the tolerance levels of macrolides and lincomycin in milk set by both the European Union and the US Food and Drug Administration. On analyzing six yoghurt samples, we found evidence for the fact that one of the six samples was contaminated with erythromycin B.

Animals↗
PubMed1982

Sequence relationships between plasmids associated with conventional MLS resistance and zonal lincomycin resistance in Streptococcus pyogenes.

By using electron microscopy of self-annealed DNA and restriction enzyme analysis, we have compared the physical maps of two group A streptococcal plasmids associated with conventional MLS resistance (pEL1; 20 Md) and zonal lincomycin resistance (pSM10419; 15 Md). Of their monomeric molecules, about 40% and 60%, respectively, are occupied by identical non-tandem inverted repeats containing sequences specifying putative replication functions. Sequence homology also exists between their resistance determinants which are located in unique DNA. Moreover, homology between additional regions of unknown function is so extensive and restriction fragment arrangement so similar that, formally, pSM10419 can be considered a deletion variant of pEL1. The results suggest that MLS and zonal lincomycin resistance have the same biochemical basis (i.e. methylation of 23S ribosomal RNA) and differ only quantitatively in the inducible control systems.

Base Sequence↗
PubMed1988

Point mutations in the 23 S rRNA genes of four lincomycin resistant Nicotiana plumbaginifolia mutants could provide new selectable markers for chloroplast transformation.

Experiments designed to establish stable chloroplast transformation require selectable marker genes encoded by the chloroplast genome. The antibiotic lincomycin is a specific inhibitor of chloroplast ribosomal activity and is known to bind to the large ribosomal subunit. We have investigated a defined region of the chloroplast 23 S rRNA genes from four lincomycin resistant Nicotiana plumbaginifolia mutants and from wild-type N. plumbaginifolia. The mutants LR415, LR421 and LR446 have A to G transitions at positions equivalent to the nucleotides 2058 and 2059 in the Escherichia coli 23 S rRNA. The mutant, LR400, possesses a G to A transition at a position corresponding to nucleotide 2032 of the E. coli 23 S rRNA.

Base Sequence↗
PubMedDate not supplied

Enhancement of polymorphonuclear leukocyte function against gram-positive aerobic organisms grown in the presence of lincomycin.

The effect of pre-incubating Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes with subinhibitory concentrations of lincomycin was studied with respect to polymorphonuclear leukocyte function against these organisms. Culturing the above organisms in the presence of lincomycin (1/4 MIC) resulted in a significant enhancement of polymorphonuclear leukocyte chemotaxis, phagocytosis and bactericidal activity against these organisms.

Bacteria↗
PubMed1998

The genes lmbB1 and lmbB2 of Streptomyces lincolnensis encode enzymes involved in the conversion of L-tyrosine to propylproline during the biosynthesis of the antibiotic lincomycin A.

The genes lmbA,B1,B2 in the lincomycin A production gene cluster of Streptomyces lincolnensis were shown to form a common transcription unit with the promoter located directly upstream of lmbA. The proteins LmbB1 (mol. mass, 18 kDa) and LmbB2 (mol. mass 34 kDa), when over-produced together in Escherichia coli, brought about enzyme activities for the specific conversion of both L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) to a yellow-colored product. The LmbB1 protein alone catalyzed the conversion of L-DOPA, but not of L-tyrosine. The purified LmbB1 protein showed a Km for L-DOPA of 258.3 microM. The L-tyrosine converting activity could not been demonstrated in vitro. The preliminary interpretation of these data suggests that the protein LmbB1 is an L-DOPA extradiol-cleaving 2,3-dioxygenase and that the protein LmbB2, either alone or in accord with LmbB1, represents an L-tyrosine 3-hydroxylase. This sequence of putative oxidation reactions on L-tyrosine seems to represent a new pathway different from the ones catalyzed by mammalian L-tyrosine hydroxylases or the wide-spread tyrosinases. The protein LmbA seemed not to be involved in this process. The labile, yellow-colored product from L-DOPA could not be converted to a picolinic acid derivative [3-(2-carboxy-5-pyridyl)alanine] in the presence of ammonia. Therefore, it probably is not a derivative of a cis, cis-3-hydroxymuconic acid semialdehyde; instead, its speculative structure represents a heterocyclic precursor of the propylhygric acid moiety of lincomycin A.

Amino Acid Sequence↗
PubMed2005

Presence of 'PSI free' LHCI and monomeric LHCII and subsequent effects on fluorescence characteristics in lincomycin treated maize.

The cause of the strong non-photochemical fluorescence quenching was examined in maize (Zea mays L.) plants that were treated with lincomycin during the 72 h period of greening. They were deficient in core complexes but seemed to contain the full complement of antennae. The following results were obtained: (1) High F(o) could not be attributed to the dark reduction of Q(A) but to the presence of a high amount of not properly organized antenna complexes due to the inhibited synthesis of reaction centres. (2) On illumination fluorescence intensity dropped considerably below F(o) within 20 s, and reached a steady state still below F(o). (3) Slowly relaxing part of non-photochemical quenching was significantly higher than in control plants. (4) De-epoxidation state was constant, and corresponded to the maximal value of the control. (5) Free Lhca1/4 dimers could be detected in all submembrane fractions, including the grana, obtained by digitonin fractionation. (6) Increase in the 679 and 700 nm fluorescence emissions could be attributed to the monomerisation of part of LHCII and to the presence of free Lhca2 or LHCII aggregates, respectively. (7) LHCII or PSII+LHCII and Lhca1/4 interaction may contribute to the increase of long-wavelength fluorescence in the granal fraction. We assume that the elevated fluorescence quenching of monomeric LHCII as well as the interaction between LHCII or PSII+LHCII and Lhca1/4 can be considered as an explanation for the extensive non-photochemical fluorescence quenching in lincomycin treated plants. The permanent presence of zeaxanthin may have contributed to the fast formation of quenching.

Anti-Bacterial Agents↗
PubMed1976

Clindamycin therapy of Staphylococcus aureus endocarditis. Clinical relapse and development of resistance to clindamycin, lincomycin and erythromycin.

A 42 year old heroin addict with Staphylococcus aureus endocarditis of the mitral valve was treated with clindamycin phosphate, 600 mg intramuscularly, every 6 hours. The initial clinical response was excellent and blood cultures became negative. On the 26th day of clindamycin therapy, fever developed and six blood cultures taken during a 72 hour period grew Staph. aureus. The patient was subsequently cured with a six week course of nafcillin plus gentamicin followed by cloxacillin. The Staph. aureus isolated before clindamycin therapy and during relapse phage-typed 29/52/52A/79/80 and was resistant to penicillin G. The susceptibility of both Staph. aureus isolates to 19 antibiotics was unchanged. However, the Stahph. aureus developed marked resistance to clindamycin, lincomycin and erythromycin, to which the original isolate was susceptible. The resistance to clindamycin and lincomycin was heterogeneous whereas the entire cell population became homogeneously highly resistant to erythromycin. These antibiotics were not inactivated in vitro by the rapidly growing resistant Staph. aureus. The most likely site of resistance was at the 50 S subunit of the bacterial ribosome.

Adult↗
PubMed1991

Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics.

Inducible resistance to lincomycin and macrolides in Streptomyces lividans TK21 results from expression of two linked genes: lrm, encoding a ribosomal RNA methyltransferase that confers high-level resistance to lincomycin with lower levels of resistance to macrolides, and mgt, encoding a glycosyl transferase that specifically inactivates macrolides using UDP-glucose as cofactor. The lrm and mgt genes have been cloned and sequenced. The deduced lrm product is a 26-kDa protein with much similarity to other ribosomal RNA methyltransferases, such as the carB, tlrA and ermE products, whereas the mgt product (predicted to be 42 kDa) resembles a eukaryotic glycosyl transferase. Macrolides that induce the lrm-mgt gene pair are substrates for inactivation by the mgt product, and the lrm product confers ribosomal resistance to such inducers.

Amino Acid Sequence↗
PubMed1975

The safety of lincomycin in pregnancy.

The progeny of mothers treated with lincomycin during the first, second, or third trimester of their pregnancy were extensively evaluated at various periods extending to 7 years after birth. As compared to a control group (mothers not receiving lincomycin), the study group did not show any more developmental anomalies of the teeth, specific physical defects, general developmental anomalties, or late developing abnormalities in speech, emotional and mental make-up, or ability to adjust to schooling, than would occur in the normal population. The relationship to clindamycin, a closely related derivative, and to antibiotic therapy during pregnancy is discussed.

Abnormalities, Drug-Induced↗
PubMed2003

In vitro susceptibilities of field isolates of Mycoplasma agalactiae to oxytetracycline, tylosin, enrofloxacin, spiramycin and lincomycin-spectinomycin.

The minimum inhibitory concentrations (MICs) of tetracycline, enrofloxacin, tylosin, spiramycin and a lincomycin:spectinomycin 1:2 combination, against 24 Sicilian isolates of Mycoplasma agalactiae, the causative organism of contagious agalactia were determined in vitro by a broth dilution method. Enrofloxacin was the most effective antimicrobial in vitro with a range of MIC values from 0.125 to 0.500 microg/ml and an MIC(50) of 0.203 and MIC(90) of 0.365 microg/ml. Using the MIC(50) and MIC(90) values the remaining four antimicrobials are ranked in order of in vitro effectiveness as follows: tylosin (MIC(50)0.292; MIC(90)0.525 microg/ml) was slightly more effective than tetracycline (MIC(50)0.296; MIC(90)0.533 microg/ml), followed by lincomycin:spectinomycin (MIC(50)0.521; MIC(90)0.938 microg/ml) and spiramycin (MIC(50)1.583; MIC(90)2.850 microg/ml). MIC values above 1.000 microg/ml were obtained using tetracycline, tylosin and spiramycin for some M. agalactiae isolates.

Animals↗
PubMed1986

The susceptibility of a strain of Leptospira interrogans serogroup icterohaemorrhagiae to amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline.

The failure of prophylactic penicillin to prevent a laboratory acquired case of Icterohaemorrhagiae leptospirosis prompted determination of the MIC and MBC of amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline for the infecting strain. Amoxycillin followed by erythromycin were the most effective, with MBCs of 0.5 mg/l after 7 days exposure and 0.1 mg/l after 21 days exposure respectively. Leptospires grew in the presence of high concentrations of tetracycline hydrochloride and oxytetracycline after prolonged incubation. This effect was less pronounced with minocycline, with MIC's of 0.025, 0.05 and 0.1 mg/l after 7, 14 and 21 days exposure respectively. The MIC of lincomycin was 0.25 mg/l at each time interval. These results support the high dose, long duration antibiotic regimens recommended in the literature.

Amoxicillin↗