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PubMed1973

Preservation of Staphylococcus aureus with unstable antibiotic resistance by drying.

Cultures of Staphylococcus aureus showing unstable resistance to kanamycin, streptomycin, lincomycin and penicillin have been preserved by drying. Particular attention has been paid to organisms showing linked resistance to pairs of these antibiotics. Recoveries of viable cells from the desiccates was high and the proportion of resistant and sensitive cells was maintained both during storage and during heating. The preservation of the organisms on ceramic beads stored in air over silica gel promises to be an effective and convenient method for maintaining staphylococcal desiccates during studies of unstable antibiotic resistance.

Bacteriological Techniques↗
PubMed1993

Hybrids of antibiotics inhibiting protein synthesis. Synthesis and biological activity.

Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of procaryotic and eucaryotic protein synthesis as well as potential antimicrobial agents. Lincophenicol (1c) was active as inhibitor of Escherichia coli ribosomal peptidyltransferase-catalyzed puromycin reaction. Both lincophenicol (1c) and sparsophenicol (1b) inhibited the binding of the iodophenol analogue of sparsomycin to E. coli ribosomes. The results are discussed in terms of a retro-inverso hypothesis advanced earlier for interpretation of biological activity of chloramphenicol (1a) and sparsophenicol (1b). Chloramlincomycin (5a) suppressed the growth of Streptococcus pyogenes with MIC 6.25 micrograms/mL.

Animals↗
PubMed2004

Antibiotic sensitivity patterns among Indian strains of avian Pasteurella multocida.

An investigation was carried out to study the antibiotic sensitivity of avian strains of Pasteurella multocida and to select an effective antimicrobial agent for control of avian pasteurellosis in India. A total of 123 strains of P. multocida recently isolated from different avian species (chicken, duck, turkey, quail, and goose), from different regions of India were subjected to antibiotic sensitivity tests using 20 different antibiotics. Absolute resistance was observed against sulfadiazine. The studies indicated that the strains were most sensitive to chloramphenicol (73.98%), followed by enrofloxacin (71.54%), lincomycin (64.23%), norfloxacin (61.79%) and doxycycline-HCl (56.91%). The majority of the strains were found to exhibit intermediate sensitivity. Chloramphenicol was selected and suggested for treatment. Antibiogram studies also revealed the emergence of multidrug-resistant strains of P. multocida among Indian poultry.

Animals↗
PubMed1975

Rapid detection and isolation of mycoplasmas from cell cultures.

An improved medium for the isolation of Mycoplasma species from contaminated cell cultures is reported. A modification of the mycoplasma detection method using the uridine/uracil uptake ratio method is described. Results obtained using this method with mycoplasma contaminated cell cultures and with contaminated cell cultures treated with the antibiotic Lincomycin are presented.

Animals↗
PubMed1998

Contribution of alpha 1-acid glycoprotein to species difference in lincosamides-plasma protein binding kinetics.

Protein binding kinetics of lincomycin (LM) and clindamycin (CM) were studied using plasma, albumin and alpha 1-acid glycoprotein (AGP) derived from humans, dogs, cattle and sheep. Based on Rosenthal plots of LM and CM, drug-binding property in plasma presented specific and non-specific binding, except for LM in cattle and sheep and for CM in sheep, where only non-specific binding was demonstrated. Dissociation constant (Kd) and binding capacity (Bmax) for specific binding and proportionality constant (PC) for non-specific binding were as follows: Kd = 3.14 mumol/L, Bmax = 15.28 mumol/L, PC = 0.19 for humans; Kd = 3.84 mumol/L, Bmax = 6.55 mumol/L, PC = 0.14 for dogs; PC = 0.12 for cattle; PC = 0.16 for sheep in LM and Kd = 0.94 mumol/L, Bmax = 12.24 mumol/L, PC = 4.98 for humans; Kd = 1.48 mumol/L, Bmax = 9.52 mumol/L, PC = 2.91 for dogs; Kd = 1.22 mumol/L, Bmax = 4.45 mumol/L, PC = 2.40 for cattle; PC = 1.48 for sheep in CM. The specific binding for each species was different, showing more difference in Bmax compared with Kd. The non-specific binding of LM was similar among species whereas that of CM was different, implying species difference. The drug-binding property of AGP for each species was all specific binding and the Kd was comparable to that obtained from plasma, indicating that AGP is a major specific binder in plasma. The lack of detection of specific binding for LM in cattle and sheep and for CM in sheep plasma could be attributable to a higher Kd and lower plasma AGP concentration compared with other species. The drug-binding property of albumin was characterized as all non-specific, without a great difference among species. Except for CM in sheep, the lower PC in albumin solution compared with that in plasma suggested the presence of another non-specific binder in plasma, i.e. lipoprotein. From the simulation of drug-binding percentage to AGP concentrations, AGP could be a major contributor to drug-plasma protein binding in pathological states. The degree of AGP-drug binding for each species could vary according to the degree of increase of AGP concentrations from a healthy to a pathological state, inducing a decrease in the unbound fraction (fp): 6.1 fold for dogs, 4.6 fold for humans, 1.8 fold for sheep and 1.4 fold for cattle in LM; 5.8 fold for dogs, 5.7 fold for cattle, 4.0 fold for humans and 1.5 fold for sheep in CM. Therefore, the disposition and efficacy of lincosamides affected by fp can be modified differently by the change of fp attributable to the alteration of plasma AGP concentration in each species.

Adult↗
PubMed1999

A multilocation clinical trial in lactating dairy cows affected with clinical mastitis to compare the efficacy of treatment with intramammary infusions of a lincomycin/neomycin combination with an ampicillin/cloxacillin combination.

A study was conducted to compare the efficacy in lactating dairy cows of intramammary infusions in quarters affected with clinical mastitis between a formulation containing 330 mg lincomycin and 100 mg neomycin in a 10-mL aqueous solution (LINCOCIN FORTE S, Pharmacia & Upjohn) and a formulation containing 75 mg ampicillin and 200 mg cloxacillin in an oil suspension (AMPICLOX, Pfizer Animal Health). This study was designed as a multicentre clinical trial involving investigators in France, Germany and Belgium and carried out according to the European Commission guidelines on Good Clinical Practices. Cows in the herds were monitored for clinical mastitis. When evidence of clinical mastitis was detected in a single quarter, a pretherapy milk sample was collected from the affected quarter. After milk sampling, the cow was assigned to one of the two treatment groups at random and treated with an intramammary infusion of one syringe of either LINCOCIN FORTE S or AMPICLOX for three successive milkings in the mastitic quarter. At 4-5, 13-15 and 20-22 days after first infusion, the veterinarian returned to the farm to conduct a clinical examination and collect milk samples from the affected quarter. Milk samples were cultured for the presence of mastitis organisms and somatic cell count (SCC) was measured. Following a 10-month study period, 256 cases were enrolled in the study. A total of 232 and 189 cases were analysed for clinical cure and for clinical-plus-bacteriological cure, respectively. The proportions of cases cured clinically and cured clinically-plus-bacteriologically were compared between the two treatment groups. Somatic cell count differences between treatment groups were also tested. The clinical cure rate for LINCOCIN FORTE S (62.5%) was significantly better than for AMPICLOX (51.8%) (P = 0.035). The clinical-plus-bacteriological cure rate was also significantly better for LINCOCIN FORTE S (38.1%) than for AMPICLOX (21.7%) (P = 0.005). Among bacteriologically cured cases, the SCC declined in both treatment groups but the SCC was significantly higher for the AMPICLOX group than for the LINCOCIN FORTE S group (P = 0.036). In conclusion, clinical cure rate, clinical-plus-bacteriological cure rate, and SCC level were significantly better with LINCOCIN FORTE S than for AMPICLOX.

Ampicillin↗
PubMed2001

Effects of altered plasma alpha-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysis.

Effects of altered plasma alpha-1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration-time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration-time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration-time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required.

Animals↗
PubMed2001

Antibacterial effect of antibiotic solution on cellular viability in canine veins.

Pretreatment of tissue by using antibiotics is a critical step to prevent microbial contamination before venous transplantation. In this study, the optimal time and temperature of antibiotic solution treatment for maintaining cellular viability with antibacterial effect were investigated. The antibiotic-nutrient solutions were composed of cefoxitin, lincomycin, vancomycin, and polymyxin B in RPMI-1640 medium. After various antibiotic solution treatment times (4, 8, and 12 h) and temperatures (4, 25, and 37 degrees C), the viabilities of cells dissociated from veins (jugular vein, femoral vein, superior vena cava, and inferior vena cava) were determined. Double staining by Griffonia simplicifolia agglutins-fluorescein isothiocyanate (GS1-FITC) and propidium iodide was used. To measure the antibacterial effect of the antibiotic solution, canine veins were artificially infected by 3 kinds of bacteria (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and were treated by antibiotic solutions as viability test conditions. After the treatment with the antibiotic solution, the tissue was minced, and the homogenized tissue fraction was cultured on standard method agar. The colony that seemed to be resistant to the antibiotic solution was counted. At 37 and 25 degrees C, the viability of whole cells decreased significantly Asymptotic Significance 2-tailed (Asymp.Sig 2-tailed) < 0.05 after 4 h of antibiotic solution treatment, whereas at 4 degrees C it began to reduce significantly after 8 h of treatment. By antibiotic solution treatment at all 3 temperatures for 4 h, no significant difference in viability of the endothelial cells and whole cells was observed. To maintain the donor vein's cellular viability until transplantation, antibiotic solution treatment for 4 h at 4 degrees C is assumed to be appropriate.

Animals↗
PubMed2001

The effect of organic acids on the control of porcine post-weaning diarrhoea.

Post-weaning diarrhoea syndrome (PWDS) of piglets is caused mainly by Enterotoxigenic Escherichia coli (ETEC) strains. Six organic acids were tested for their efficacy in the control of PWDS, using a total of 384 weaned piglets, in eight groups, during a 28-day period. One group (negative control) was offered a diet free of antimicrobials, one group (positive control) was offered the same diet medicated with 44 p.p.m. of lincomycin and 44 p.p.m. spectinomycin (Lincospectin 22 premix, Upjohn), and six groups were offered feed supplemented with either 1.0 per cent propionic acid, 1.6 per cent lactic acid, 1.2 per cent formic acid, 1.2 per cent malic acid, 1.5 per cent citric acid or 1.5 per cent fumaric acid. Groups were compared with regard to the appearance of clinical signs, mortality, weight gain and feed conversion. All groups supplemented with organic acids had reduced incidence and severity of diarrhoea, and performed significantly better than the negative control group (P<0.05). At the end of the trial, ETEC strains were detected in the control group not receiving antibiotics but not in the treated group. Organic acids and especially lactic acid are a useful tool in controlling PWDS.

Animal Feed↗
PubMed2004

Populations of photoinactivated photosystem II reaction centers characterized by chlorophyll a fluorescence lifetime in vivo.

Photosystem (PS) II centers, which split water into oxygen, protons, and electrons during photosynthesis, require light but are paradoxically inactivated by it. Prolonged light exposure concomitantly decreased both the functional fraction of PSII reaction centers and the integral PSII chlorophyll (Chl) a fluorescence lifetime in leaf segments of Capsicum annuum L. Acceleration of photoinactivation of PSII by a pretreatment with the inhibitors/uncoupler lincomycin, DTT, or nigericin further reduced PSII Chl a fluorescence lifetimes. A global analysis of fluorescence lifetime distributions revealed the presence of at least two distinct populations of photoinactivated PSII centers, one at 1.25 ns, and the other at 0.58 ns. Light treatment first increased the 1.25-ns component, a weak quencher, at the expense of a component at 2.22 ns corresponding to functional PSII centers. The 0.58-ns component, a strong quencher, emerged later than the 1.25-ns component. The strongly quenching PSII reaction centers could serve to avoid further damage to themselves and protect their functional neighbors by acting as strong energy sinks.

Anti-Bacterial Agents↗
PubMed1970

Biogenesis of mitochondria. 18. A new class of cytoplasmically determined antibiotic resistant mutants in Saccharomyces cerevisiae.

New mutant yeasts resistant to the antibiotics chloramphenicol and mikamycin were isolated. They are mitochondrial mutants, characterized by several criteria as cytoplasmically determined. Biochemical studies show that amino acid incorporation into protein in vitro by mitochondria isolated from cells resistant or sensitive to mikamycin or chloramphenicol is inhibited by these antibiotics. Although aerobically-grown resistant strains of Saccharomyces cerevisiae are not affected by mikamycin or chloramphenicol, it is found that the mitochondrial protein-synthesizing system of anaerobically grown cells is inhibited in vivo. Cross resistance among the antibiotics chloramphenicol, mikamycin, erythromycin, lincomycin, carbomycin, and spiramycin is reported. All erythromycin resistant mutants, unlike the others, are resistant to erythromycin in vivo and in vitro. The results indicate that some of the cytoplasmic mutations (mikamycin and chloramphenicol resistance) are expressed at the mitochondrial membrane, whereas others (erythromycin resistance) possibly reflect changes in mitochondrial ribosomal proteins. We further suggest that conformational changes, either in the membranes or ribosomes, are likely to account for the observed antibiotic cross resistances.

Anti-Bacterial Agents↗
PubMed1971

Hydrolysis of fMet-tRNA by peptidyl transferase.

Escherichia coli and rabbit reticulocyte (f[(3)H]Met-tRNA.AUG.ribosome) intermediates undergo hydrolysis, with release of f[(3)H]methionine, upon addition of tRNA or CpCpA in the presence of acetone. This ribosomal catalyzed reaction has similar requirements, pH optimum, and antibiotic sensitivity to those of peptidyl transferase. Two antibiotics, lincomycin with E. coli ribosomes and anisomycin with reticulocyte ribosomes, inhibit peptide-bond formation and transesterification activities of peptidyl transferase, but stimulate hydrolysis of f[(3)H]Met-tRNA. Earlier studies have suggested peptidyl transferase activity is essential for R factor-dependent hydrolysis of f((3)H)Met-tRNA. These studies indicate that peptidyl transferase has the capacity for f((3)H)Met-tRNA hydrolysis and, therefore, may be responsible for peptidyl-tRNA cleavage during peptide chain termination.

Animals↗
PubMed1969

Biogenesis of mitochondria. XI. A comparison of the effects of growth-limiting oxygen tension, intercalating agents, and antibiotics on the obligate aerobe Candida parapsilosis.

Growth under conditions of oxygen restriction results in a generalized decrease in the definition of the mitochondrial membranes, a decrease in the mitochondrial cytochromes, and a decrease in citric acid cycle enzymes of the obligate aerobic yeast Candida parapsilosis. Addition of unsaturated fatty acids and ergosterol to cultures exposed to limited oxygen results in improved definition of the mitochondrial membranes and an increase in the total mitochondrial cytochrome content of the cells. Euflavine completely inhibits mitochondrial protein synthesis in vitro. Its in vivo effect is to cause the formation of giant mitochondrial profiles with apparently intact outer membranes and modified internal membranes; the cristae (in-folds) appear only as apparently disorganized remnants while the remainder of the inner membrane seems intact. Cytochromes a, a(3), b, and c(1) are not synthesized by the cells in the presence of euflavine. Ethidium appears to have effects identical to those of euflavine, whereas chloramphenicol, lincomycin, and erythromycin have similar effects in principle but they are less marked. The effects of all the inhibitors are freely reversible after removal of the drugs. The results are discussed in terms of a functionally three-membrane model of the mitochondrion. In addition, the phylogenetic implications of the observed differences between this organism and the facultative anaerobic yeasts are considered.

Acridines↗
PubMed1976

Periodic variations in the ratio of free to thylakoid-bound chloroplast ribosomes during the cell cycle of Chlamydomonas reinhardtii.

The ratio of free to thylakoid-bound chloroplast ribosomes in Chlamydomonas reinhardtii undergoes periodic changes during the synchronous light-dark cycle. In the light, when there is an increase in the chlorophyll content and synthesis of thylakoid membrane proteins, about 20-30% of the chloroplast ribosomes are bound to the thylakoid membranes. On the other hand, only a few or no bound ribosomes are present in the dark when there is no increase in the chlorophyll content. The ribosome-membrane interaction depends not only on the developmental stage of the cell but also on light. Thus, bound ribosomes were converted to the free variety after cultures at 4 h in the light had been transferred to the dark for 10 min. Conversely, a larger number of chloroplast ribosomes became attached to the membranes after cultures at 4 h in the dark had been illuminated for 10 min. Under normal conditions, when there was slow cooling of the cultures during cell harvesting, chloroplast polysomal runoff occurred in vivo leading to low levels of thylakoid-bound ribosomes. This polysomal runoff could be arrested by either rapid cooling of the cells or the addition of chloramphenicol or erythromycin. Each of these treatments prevented polypeptide chain elongation on chloroplast ribosomes and thus allowed the polyosomes to remain bound to the thylakoids. Addition of lincomycin, an inhibitor of chain initiation on 70S ribosomes, inhibited the assembly of polysome-thylakoid membrane complex in the light. These results support a model in which initiation of mRNA translation begins in the chloroplast stroma, and the polysome subsequently becomes attached to the thylakoid membrane. Upon natural chain termination, the chloroplast ribosomes are released from the membrane into the stroma.

Cell Division↗
PubMed1983

Sites of synthesis of chloroplast ribosomal proteins in Chlamydomonas.

Cells of Chlamydomonas reinhardtii were pulse-labeled in vivo in the presence of inhibitors of cytoplasmic (anisomycin) or chloroplast (lincomycin) protein synthesis to ascertain the sites of synthesis of chloroplast ribosomal proteins. Fluorographs of the labeled proteins, resolved on two-dimensional (2-D) charge/SDS and one-dimensional (1-D) SDS-urea gradient gels, demonstrated that five to six of the large subunit proteins are products of chloroplast protein synthesis while 26 to 27 of the large subunit proteins are synthesized on cytoplasmic ribosomes. Similarly, 14 of 31 small subunit proteins are products of chloroplast protein synthesis, while the remainder are synthesized in the cytoplasm. The 20 ribosomal proteins shown to be made in the chloroplast of Chlamydomonas more than double the number of proteins known to be synthesized in the chloroplast of this alga.

Anisomycin↗
PubMed1976

Tobramycin in pediatric use.

The new aminoglycoside antibiotic, tobramycin, was used for treatment of gram-negative and staphylococcal infection in 38 neonates, infants, and children in a pediatric surgical unit. Levels of drug in serum after administration by intramuscular, intravenous, and intraperitoneal routes were monitored, and control of infections was generally good within the therapeutic range of 2.0-10.0 mug/ml with a standard dosage regimen of approximately 5 mg/kg per day. Impairment of renal function and concurrent lincomycin therapy were important factors causing variation of levels in serum outside this range. Levels of tobramycin in cerebrospinal fluid after intraventricular instillation varied greatly in one patient, but were satisfactory in another. Clinical and bacteriological assessment of results indicated only two failures of treatment, although infection with a known resistant organism supervened in three cases. Screening for renal, hepatic, and hematological toxicity revealed only one case of transient and reversible renal impairment. Response to tobramycin therapy was generally rapid and satisfactory in a group of young patients with moderately severe infections, many of which were complicated by the presence of a congenital anomaly.

Anti-Bacterial Agents↗
PubMed1977

Bacteremia due to Bacteroidacceae: a review of 92 cases.

The clinical courses of 92 patients who had bacteremia due to Bacteroidaceae were reviewed. The overall mortality rate was 21% (19 patients). There was no significant difference between mortality rates when patients were grouped by anticipated clinical course of underlying disease (nonfatal, ultimately fatal, and rapidly fatal) and when they were grouped by type of antibacterial therapy (appropriate, including clindamycin, chloramphenicol, lincomycin, and carbenicillin; or inappropriate, signifying no antibiotic treatment or treatment with antibiotics other than the four listed above). However, there was a correlation between recovery of the patient and portal of entry of the infectious agent; patients whose source of infection was the gastrointestinal tract had a mortality rate of 29% (17 of 58 patients), whereas there were no deaths among the 26 women whose presumed source of bacteremia was the genital tract. Increasing age appeared to be an important factor as well; 17 of 19 deaths occurred in patients who were older than 40 years. There was no significant difference between the mortality rate of patients who were treated with clindamycin (15%, eight of 52 patients) and that of patients who were treated with chloramphenicol (44%, four of nine).

Adult↗
PubMed1977

Rapid bioassay for clindamycin alone and in the presence of aminoglycoside antibiotics.

A rapid bioassay for determination of concentrations of clindamycin in serum was developed with use of a strain of Lancefield group B Streptococcus (Streptococcus agalactiae) that is uniformly resistant to aminoglycoside antibiotics, tetracycline, and polymyxin. An agar diffusion assay system was used that included the addition of patient's sera and three standard concentrations of clindamycin to 5-mm wells cut in the seeded agar. Pretreatment of serum with penicillinase allowed measurement of clindamycin in the presence of penicillins and cephalosporins by the same assay method. Assays of clindamycin in serum using this system could be read routinely in as little as 4 hr and allowed determination of levels of drug in serum of 2.5-40 microgram/ml. Linear regression analyses indicated that values obtained by this assay compared favorably with the results obtained with use of Bacillus subtilis strain ATCC 6633 or Sarcina lutea strain ATCC 9341 (American Type Culture Collection, Rockville, Md.). Repetitive measurement of sera with known concentrations of clindamycin indicated the average deviation to be +/- 10%. Seeded bioassay plates could be prepared in advance and stored at 2 C-8 C for up to one week before use. This assay may also be used for measurement of lincomycin, erythromycin, vancomycin, and certain beta-lactam antibiotics in the presence of aminoglycosides.

Aminoglycosides↗