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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↗

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↗

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↗

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↗

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↗

PubMedDate not supplied

A method for the analysis of lincomycin in porcine and bovine kidney.

A method of analysis has been developed for the estimation of lincomycin in porcine and bovine kidney. The method employed high performance liquid chromatography and Sep-Pak clean-up of methanolic tissue extracts and nitrogen specific gas chromatographic detection. Using spiked (0.1 mg kg-1) extracts recoveries in the range 40-50% were obtained. Analysis at the 0.05 mg kg-1 level is possible. Fifty four samples of kidney destined for UK sale were analysed for the presence of this drug. No samples were found to contain lincomycin.

Animals↗

PubMed1975

The spectrum of colitis associated with lincomycin and clindamycin therapy.

Ten cases of protracted diarrheal illness after the oral administration of lincomycin or clindamycin in standard dosages were observed in previously healthy subjects. An abrupt onset of diarrhea, crampy abdominal pain, fever, and leukocytosis was observed one to 12 days after discontinuation of the drug. Proctoscopic examination revealed erythematous friable mucosa covered with small raised, yellowish-white plaques that were sometimes confluent. Barium contrast studies of the colon demonstrated irregular shaggy mucosa, ulcerations, cobblestone appearance, and thumb printing. Rectal bipsy showed acute inflammation with pseudomembranes with focal or superficial ulcerations. All patients had a protracted course but recovered with supportive management. Follow-up barium enemas and proctoscopy were done on all patients and were normal. A history of diarrhea, fever, and mucosal changes seen on proctoscopy in a patient who has recently received one of these antibiotics should raise the possibility of colitis associated with clindamycin and lincomycin therapy.

Adult↗

PubMed1989

Inducible ribosomal RNA methylation in Streptomyces lividans, conferring resistance to lincomycin.

Streptomyces lividans TK21 possesses inducible ribosomal RNA methylase activity that confers high-level resistance to lincomycin and lower levels of resistance to certain macrolides. The methylase gene (designated lrm) is inducible by erythromycin and other macrolides and also by celesticetin (a lincosamide) but not by lincomycin. The lrm enzyme monomethylates the N6-amino group of adenosine at position 2058 within 23S-like ribosomal RNA.

Anti-Bacterial Agents↗

PubMed1978

Interaction between erythromycin and lincomycin in Streptococcus pyogenes.

Ten strains of Streptococcus pyogenes isolated were moderately resistant to erythromycin and highly but paradoxically resistant to lincomycin, and they showed antagonism between the two antibiotics. Another strain was moderately resistant to erythromycin and sensitive to lincomycin, and it showed synergism between the two antibodies.

Dose-Response Relationship, Drug↗

PubMed1986

The effect of lincomycin on exoprotein production by Vibrio cholerae.

Lincomycin has a differential effect on exoprotein production by Vibrio cholerae. The production of some proteins, such as cholera toxin and deoxyribonuclease, is stimulated by low concentrations of the drug while production of other proteins, such as protease and alkaline phosphatase, is unaffected. Possible mechanisms of the lincomycin effect are discussed.

Alkaline Phosphatase↗

PubMed1986

Chloramphenicol, lincomycin and oxytetracycline disposition in calves with experimental pneumonic pasteurellosis.

The effects of pneumonia on the pharmacokinetics of chloramphenicol, lincomycin, and oxytetracycline were evaluated in two-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures directly through the thoracic wall into each lung. Six days prior to induction of pneumonia, the antibiotics were administered in a single i.v. dose. The antibiotics were administered again 48 (i.v.), 60 and 72 h (i.m.) following injection of P. haemolytica. The pharmacokinetics of chloramphenicol (25 mg/kg) and lincomycin (10 mg/kg) were not significantly different in calves with pneumonia. The hybrid rate constant beta for oxytetracycline was increased in calves with pneumonia from 0.0034 +/- 0.0003/min to 0.0048 +/- 0.0007/min between 2 h and 8 h. Thus the elimination half-life in serum was shortened from 212.4 +/- 20.3 min to 149.3 +/- 19.5 min. In addition, there was an apparent but not statistically significant decrease in K12 with pneumonia. These findings accentuate the need for observance of 12-h dose intervals with oxytetracycline.

Animals↗