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Colitis and diarrhoea: a problem with antibiotic therapy.

During a 19-month study the incidence of diarrhoea and colitis was estimated in 1158 orthopaedic inpatients admitted to the Guy's group of hospitals. The highest incidence of diarrhoea followed the use of lincomycin (22.2 per cent), ampicillin with cloxacillin (17.2 per cent), clindamycin (15.3 per cent) and combined therapy with cloxacillin and tetracycline (12.5 per cent). There were 3 documented cases of colitis; 2 followed lincomycin and 1 clindamycin. The incidence and relationship of antibiotic-related diarrhoea and colitis to possible aetiological factors are discussed. In orthopaedic inpatients, in whom lincomycin and clindamycin are often the antibiotics of choice, their continued use appears to be fully justified by the low incidence of colitis. However, if a patient receiving treatment with either of these antibiotics does develop diarrhoea, the antibiotic should be discontinued immediately, to reduce the risk of subsequent colitis.

Adolescent↗

Toxic shock syndrome toxin-1 (TSST-1): influence of its production by subinhibitory antibiotic concentrations.

Using seven different toxic shock syndrome toxin-1 (TSST-1) producing Staphylococcus aureus strains, we examined the influence on growth and toxin production of subinhibitory concentrations of clindamycin, erythromycin, lincomycin, kanamycin, tetracycline and tunicamycin. The behaviour of six S. aureus (= W/MT-strains) was identical, the one of S. aureus MN8 was different in part. Using the different subinhibitory antibiotic concentrations, bacterial growth was inhibited by tunicamycin only. Toxin production was influenced by clindamycin, erythromycin, lincomycin, kanamycin and tetracycline without simultaneous changes in the number of cells; MN8 was more sensitive to clindamycin and lincomycin than W/MT strains. Very small differences or no differences at all were found between the two bacterial groups in experiments using erythromycin, kanamycin and tetracycline. Tunicamycin caused elevated TSST-1 concentrations of 100% (MN8) or 65% (W/MT) above the control level if used at concentrations of 4 mg/l or 16 mg/l respectively; this result is interpreted as a higher output of TSST-1 caused by the damage to the bacterial cell wall. From these results it is not possible to conclude that different mechanisms of regulation of TSST-1 expression exist between S. aureus MN8 and the other TSST-1 positive S. aureus strains.

Anti-Bacterial Agents↗

Nosocomial outbreak of Clostridium difficile diarrhea in a pediatric service.

An outbreak of nosocomial diarrhea that occurred in a pediatric orthopedic service between 1 December 1993 and 15 April 1994 is reported. A total of 37 patients (mean age, 9.6 years; range, 2 months-19.3 years) were involved in the outbreak, including six patients with bacteriologically documented Clostridium difficile infection. A multivariate analysis identified lincomycin treatment for at least three days as the only significant risk factor. Stool samples from four asymptomatic patients were also positive for Clostridium difficile and its cytotoxins. Isolates from all patients belonged to serogroup C, were highly resistant to lincomycin, and exhibited the same restriction pattern by pulsed-field gel electrophoresis. The outbreak ended after treatment with lincomycin was discontinued and hygiene control measures were implemented.

Adolescent↗

Photoinactivation of photosystem II complexes and photoprotection by non-functional neighbours in Capsicum annuum L. leaves.

Leaf segments from Capsicum annuum plants grown at 100 micromol photons m(-2) s(-1) (low light) or 500 micromol photons m(-2) s(-1) (high light) were illuminated at three irradiances and three temperatures for several hours. At various times, the remaining fraction (f) of functional photosystem II (PS II) complexes was measured by a chlorophyll fluorescence parameter (1/Fo -1/Fm, where Fo and Fm are the fluorescence yields corresponding to open and closed PS II traps, respectively), which was in turn calibrated by the oxygen yield per saturating single-turnover flash. During illumination of leaf segments in the presence of lincomycin, an inhibitor of chloroplast-encoded protein synthesis, the decline of f from 1.0 to about 0.3 was mono-exponential. Thereafter, f declined much more slowly, the remaining fraction (approximately equals 0.2) being able to survive prolonged illumination. The results can be interpreted as being in support of the hypothesis that photoinactivated PS II complexes photoprotect functional neighbours (G. Oquist et al. 1992, Planta 186: 450-460), provided it is assumed that a photoinactivated PS II is initially only a weak quencher of excitation energy, but becomes a much stronger quencher during prolonged illumination when a substantial fraction of PS II complexes has also been photoinactivated. In the absence of lincomycin, photoinactivation and repair of PS II occur in parallel, allowing f to reach a steady-state value that is determined by the treatment irradiance, temperature and growth irradiance. The results obtained in the presence and absence of lincomycin are analysed according to a simple kinetic model which formally incorporates a conversion from weak to strong quenchers, yielding the rate coefficients of photoinactivation and of repair for various conditions, as well as gaining an insight into the influence off on the rate coefficient of photoinactivation. They demonstrate that the method is a convenient alternative to the use of radiolabelled amino acids for quantifying photoinactivation and repair of PS II in leaves.

Capsicum↗

Prophylactic systemic antibiotics in colorectal surgery.

The prophylactic value of gentamicin combined with either lincomycin or metronidazole in 52 patients undergoing colorectal surgery was investigated. The results confirmed the value of this practice. In a control group, the sepsis-rate was 48% with 1 death attributable to sepsis, compared with a sepsis-rate of 4% in the treated group. The combination of gentamicin and lincomycin was effective against sepsis but pseudomembranous colitis developed in 2 of the 14 patients treated with this combination of drugs. Lincomycin was discontinued, and when metronidazole was substituted the results were equally good and there were no toxic side-effects.

Abscess↗

Antimicrobial susceptibility testing of Mycoplasma hyosynoviae isolated from pigs during 1968 to 1971 and during 1995 and 1996.

This study was conducted to compare the Minimal Inhibitory Concentrations (MICs) for enrofloxacin, lincomycin, tetracycline, tiamulin and tylosin, of Mycoplasma hyosynoviae, isolated from pigs at notably different intervals (1968-71 and 1995-96). Each group comprised 21 low passage isolates and a Danish reference strain (M60) and the type strain (S16). MICs were determined in liquid medium with both initial and final readings. Enrofloxacin, lincomycin, tetracycline and tiamulin were active against all isolates, and tiamulin showed the highest activity. For tylosin all the isolates from 1968-71 were highly susceptible, whereas the isolates from 1995-96 could be divided into a highly susceptible (nine isolates) and relatively resistant (12 isolates) group. This difference between old and new strains was statistically significant (p = 0.0000415). The remaining agents, enrofloxacin, lincomycin, tiamulin and tetracycline, showed an unaltered good activity against M. hyosynoviae. The resistance to tylosin seems now to occur so often that this antibiotic cannot be recommended for therapeutic use any more. The most probable explanation for the emergence of resistance is the intensive use of tylosin during many years for therapy and growth promotion.

Animals↗

Degradation of the Photosystem II D1 and D2 proteins in different strains of the cyanobacterium Synechocytis PCC 6803 varying with respect to the type and level of psbA transcript.

The turnover of the D1 and D2 proteins of Photosystem II (PSII) has been investigated by pulse-chase radiolabeling in several strains of the cyanobacterium Synechocystis PCC 6803 containing different types and levels of the psbA transcript. Strains lacking psbA1 and psbA3 gene and containing high levels of the psbA2 transcript showed the selective synthesis of D1 whose degradation could be slowed down by the protein synthesis inhibitor lincomycin. In contrast, in strains containing just the psbA3 gene, the intensity of the D1 protein labeling was lower and labeling of the D2 and CP43 proteins was stimulated in comparison to the psbA2-containing strains. In addition, the rate and selectivity of the D1 degradation and its dependence on the presence of lincomycin was proportional to the level of the psbA3 transcript in the particular strain. Consequently, there was parallel, lincomycin-independent and slowed-down breakdown of the D1 and D2 proteins in strains with the lowest level of psbA3 transcript. These results are discussed in terms of a model in which the rate of D1 and D2 degradation in cyanobacteria is affected not only by the rate of PSII photodamage, but also by the availability of newly synthesized D1 protein. Moreover, the comparison of the non-oxygen-evolving D1 mutants D170A** and Y161F*** differing by the presence of tyrosine Z has indicated a minor role of the oxidized form of this secondary PSII electron donor in the donor side mechanism of D1 and D2 protein breakdown.

Algal Proteins↗

Multiple plastid signals regulate the expression of the pea plastocyanin gene in pea and transgenic tobacco plants.

The expression of nuclear genes encoding photosynthesis-related proteins is regulated by signals from plastids. To investigate how the pea PetE gene encoding plastocyanin is regulated by plastid signals, the effects of norflurazon, lincomycin and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), specific inhibitors of plastid-located processes generating plastid signals, have been examined. RNA-gel blot analysis of 7-day-old pea and tobacco seedlings containing the pea PetE gene showed that treatment with norflurazon and lincomycin, but not DCMU, decreased the accumulation of transcripts of pea PetE and endogenous Lhcb1 genes. Analysis of chimeric PetE gene constructs in tobacco seedlings showed that an intact PetE mRNA 5' terminus and elements within the PetE coding region were required to confer sensitivity to norflurazon and lincomycin, suggesting post-transcriptional regulation. Analysis of 4-week-old tobacco plants containing chimeric PetE constructs showed that DCMU treatment decreased the accumulation of pea PetE and Lhcb1 transcripts, but had opposite effects on the transcription of the genes in nuclear run-on assays. DCMU upregulated transcription from the pea PetE promoter whereas transcription of tobacco Lhcb1 genes was decreased. These experiments provide evidence for multiple plastid signals operating at different developmental stages and affecting transcriptional and post-transcriptional processes regulating expression of the pea PetE gene.

Diuron↗

The effects of antibiotics in the weanling pig diet on growth and the excretion of volatile phenolic and aromatic bacterial metabolites.

The purpose of this study was to investigate the effects of dietary antibiotic supplementation on the fecal urinary excretion of volatile phenolic and aromatic bacterial metabolites by the weanling pig, and to determine if a relationship exists between an exposure to these metabolites and growth performance. Wealing pigs were fed a basal diet, supplemented with either 110 ppm chlortetracycline, 110 ppm sulfamethazine and 55 ppm penicillin, 40 ppm lincomycin sulfate, or no antibiotics, for 30 days. Pigs on the chlortetracycline-sulfamethazine-penicillin diet on the average tended to grow at a faster rate, attained a higher percentage weight gain, and weighed slightly more than pigs on either the lincomycin sulfate or no antibiotic diets. Under all treatments, p-cresol was the predominant metabolite of the volatile phenolic and aromatic metabolites detected in feces and urine, with the urine accounting for 88% of its total daily excretion. Pigs on the chlortetracycline-sulfamethazine-penicillin diet excreted less urinary p-cresol than pigs on either the lincomycin sulfate or no antibiotic diets. Total p-cresol excretion expressed on the metabolic body size, resulted in significant treatment differences. Regression analysis of percentage body weight gain on urinary p-cresol excretion gave a negative correlation coefficient (r = -0.73). The results suggest that intestinal p-cresol production may be responsible for depressing the growth of the weanling pig.

Animals↗

Efficacy of lincosaminide antibiotics in the treatment of experimental staphylococcal mastitis in lactating mice.

Staphylococcus aureus is a frequent cause of bovine mastitis worldwide. A model that may predict the efficacy of antimicrobial agents in the treatment of bovine mastitis induced by Staph. aureus was developed in lactating mice. Infection was established by the inoculation of lactating CF1 mice with Staph. aureus into the mammary gland via the teat duct. At the dose of bacteria used, 85-90% of the inoculated, untreated animals developed a nonlethal, acute mastitis within 48 h. Antibiotic treatment was administered subcutaneously or by the intramammary route. Lincosaminide antibiotics including lincomycin, clindamycin, and pirlimycin were evaluated in this system. Other compounds which have been used in therapy of bovine mastitis including novobiocin, penicillin G, ampicillin, cloxacillin and rifamycin-SV were used as reference antibiotics. Pirlimycin was the most effective of the antibiotics tested in this standardized system. Depending upon the route of administration, this novel lincosaminide was 15 to 95-fold more effective than clindamycin, three- to six-fold better than lincomycin, two- to ten-fold more effective than novobiocin, 13- to 17-times more effective than cloxacillin and 8- to 22-times better than rifamycin-SV on a weight-dose comparison. Penicillin G and ampicillin were the least effective drugs tested against mastitis induced by the beta-lactamase producing strain of Staph. aureus used in these assays. Pharmacokinetic experiments suggested that the greater effectiveness of pirlimycin compared to clindamycin and lincomycin was due to increased affinity for and prolonged retention in the mammary gland.

Animals↗

In-vitro antimicrobial activity of HMR 3004 (RU 64004) against erythromycin A-sensitive and -resistant Corynebacterium spp. isolated from clinical specimens.

We studied the in-vitro activity of HMR 3004 (RU 64004), a new ketolide, against 161 clinical isolates of Corynebacterium spp. including isolates resistant to erythromycin A, josamycin and lincomycin. HMR 3004 was active against all erythromycin A-sensitive isolates as well as against 75.8% and 45.4% of erythromycin A-intermediate and -resistant isolates, respectively. In contrast, HMR 3004 was active against 40 (46.5%) of 86 isolates resistant to erythromycin A, josamycin and lincomycin as well as against two isolates that were resistant to erythromycin A and lincomycin but not resistant (i.e. susceptible or intermediate) to josamycin.

Anti-Bacterial Agents↗

Macrolide-lincosamide-streptogramin resistance patterns in Clostridium perfringens from animals.

Different patterns of resistance against commonly used macrolide, lincosamide, and streptogramin antibiotics were found in Clostridium perfringens of animal origin. The patterns were designated as (i) macrolide-lincosamide-streptogramin group B generalized resistance, (ii) macrolide-lincosamide generalized resistance, (iii) macrolide-lincosamide inducible resistance, and (iv) macrolide-lincosamide-streptogramin low-level generalized resistance. The strains of the fourth pattern were able to inactivate pristinamycin and virginiamycin. The macrolide-susceptible strains showed a bimodal distribution of lincomycin and clindamycin susceptibility levels. The susceptible strains were inhibited by 0.25 micrograms of lincomycin per ml and 0.03 micrograms of clindamycin per ml. The low-level resistant strains were inhibited at concentrations of 2 to 4 micrograms of lincomycin per ml and 0.5 to 2 micrograms of clindamycin per ml.

Animals↗

In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae.

Sedecamycin (lankacidin A), one of the lankacidin-group antibiotics, showed potent activity against Treponema hyodysenteriae. The MICs of sedecamycin against 79 field isolates of T. hyodysenteriae ranged from 0.78 to 12.5 micrograms/ml, the MIC for 90% of the strains tested (MIC90) being 3.13 micrograms/ml. The protective and therapeutic effects of sedecamycin were compared with those of carbadox, tiamulin, and lincomycin against experimental infection with T. hyodysenteriae in mice. The protective effect of sedecamycin was similar to that of carbadox, two times more potent than that of tiamulin, and three times greater than that of lincomycin. In the therapeutic test, sedecamycin showed activity similar to that of carbadox and was two times more active than both tiamulin and lincomycin. At doses of 10 mg or more of sedecamycin per kg, the recurrence of shedding of T. hyodysenteriae into the feces of mice was not detected for at least 8 weeks postmedication.

Animals↗

Lincosamide antibiotics stimulate dissociation of peptidyl-tRNA from ribosomes.

At nonpermissive temperatures the peptidyl-tRNA hydrolase of pth(Ts) bacterial mutants is inactivated, and cells accumulate peptidyl-tRNA and die. Doses of erythromycin, lincomycin, or clindamycin that inhibited the growth of antibiotic-hypersensitive DB-11 pth+ cells accelerated the killing of DB-11 pth(Ts) cells at nonpermissive temperatures. Erythromycin and lincomycin also stimulated the accumulation of peptidyl-tRNA. Lincomycin and clindamycin stimulated peptidyl-tRNA dissociation from ribosomes.

Anti-Bacterial Agents↗

Erythromycin-inducible resistance in Staphylococcus aureus: requirements for induction.

At least two functionally different types of ribosomes are found in strains of Staphylococcus aureus which display "dissociated" resistance to erythromycin. One type of ribosome is found under conditions of growth in ordinary nutrient broth, and the second is formed during growth in the presence of erythromycin. In these strains, erythromycin acts as an inducer of resistance to three different classes of inhibitors of the 50S ribosomal subunit-the macrolides, lincosamides, and streptogramin B-type antibiotics. The optimal inducing concentration of erythromycin is between 10(-8) and 10(-7)m. Concentrations as low as 10(-9)m can produce a 10-fold increase in resistant cells over the uninduced, background level, whereas concentrations greater than 10(-7)m block induction owing to inhibition of protein synthesis. Resistant cells begin to appear within 5 to 10 min after addition of erythromycin (to 10(-7)m), and within 40 min (i.e., about one generation) more than 90% of the entire culture is resistant to erythromycin as well as to lincomycin and vernamycin B(alpha). A resistant culture becomes sensitive if grown for 90 min in the absence of erythromycin. The process of induction is inhibited by chloramphenicol and streptovaricin, which inhibit protein and ribonucleic acid synthesis, respectively, but not by novobiocin, which inhibits deoxyribonucleic acid synthesis. Resistant cells produced in this manner fail to concentrate (14)C-erythromycin and (14)C-lincomycin, but not (14)C-chloramphenicol. Constitutively erythromycin-resistant strains which do not require the presence of erythromycin for expression of resistance can be selected on media containing antibiotics which belong to any one of the three classes. Two patterns of constitutive resistance have been found. These are (i) generalized constitutive resistance-which involves resistance in the absence of erythromycin to all members of each of the three cited classes of 50S subunit inhibitors which were tested, and (ii) partial constitutive resistance-which involves different degrees of resistance, in the absence of erythromycin, to various members of the three classes. Several different patterns of variable constitutivity are possible. 50S ribosomal subunits isolated from induced or constitutively resistant cells show decreased ability to bind erythromycin and lincomycin, and possible enzymatic inactivation of these antibiotics has been rigorously excluded. The induced change, therefore involves modification of ribosome structure rather than modification of the antibiotic.

Anti-Bacterial Agents↗

Minimal inhibitory concentrations of five antimicrobials against Treponema hyodysenteriae and Treponema innocens.

The minimal inhibitory concentrations of carbadox, dimetridazole, lincomycin, ronidazole, and tiamulin against isolates of Treponema hyodysenteriae and Treponema innocens were determined by an agar-dilution method. The results obtained indicated that tiamulin was the most effective antimicrobial in vitro against T. hyodysenteriae, followed by carbadox. Dimetridazole, lincomycin, and ronidazole had poor efficacy in vitro against the T. hyodysenteriae isolates. Isolates of T. innocens were more sensitive to the various antimicrobials. Carbadox and tiamulin were the most effective in vitro, followed by ronidazole, dimetridazole, and lincomycin.

Animals↗

Efficacy of a nonantimicrobial cream administered topically for treatment of digital dermatitis in dairy cattle.

OBJECTIVE: To compare efficacy of a topically administered nonantimicrobial cream with that of lincomycin for treatment of digital dermatitis in dairy cattle. DESIGN: Randomized clinical trial. ANIMALS: 98 cows from a commercial Holstein dairy herd. PROCEDURE: Cows with active lesions of digital dermatitis identified on a single observation day were randomly assigned to receive a nonantimicrobial cream, lincomycin paste, or no treatment. Cows were examined approximately every 4 weeks for 130 days after treatment for lesion maturity score, score for signs of pain, lesion size, and lesion activity. RESULTS: 29 days after a single treatment, both treated groups had significantly reduced scores for signs of pain, lesion activity, lesion size, and the decision to retreat, compared with findings in the untreated group. Efficacy of the 2 treatments was not significantly different for decreasing pain score or lesion activity or for increasing lesion maturity score, but lincomycin was significantly more efficacious in decreasing lesion size and avoiding retreatment. By use of multivariate logistic regression, lactation number was a significant treatment effect modifier on the outcome of a healed lesion after treatment. Cows with > or = 3 lactations were more likely to have a healed lesion at 29 days, compared with first- and second-lactation cows. CONCLUSIONS AND CLINICAL RELEVANCE: Because antimicrobial treatments for digital dermatitis in cows require a veterinarian's prescription, the nonantimicrobial cream could serve as a viable but less consistently effective alternative to antimicrobials and could be applied by veterinarians, hoof trimmers, and others.

Administration, Topical↗

Antimicrobial in vitro susceptibility of actinomyces israelii and arachnia propionica.

46 reference strains and clinical isolated of Actinomyces israelli and 8 strains of Arachnia propionica--the causative microorganisms of actinomycosis in man--were tested for their in vitro susceptibility to penicillin, sulfaisodimidine, erythromycin, tetracycline, lincomycin, clindamycin, metronidazole and tinidazole by the agar dilution method. All strains were susceptible to benzylpenicillin (minimum inhibitory concentrations, MICs of less than or equal to 0.064 mug/ml). Many strains were resistant in vitro to sulfaisodimidine (MICs 4.0-32.0 mug/ml). Erythromycin, tetracycline, clindiamycin and lincomycin possessed in vitro activity at concentrations readily attainable in serum. Due to adverse side-effects associated with clindamycin and lincomycin therapy, erythromycin and tetracycline may be the best alternative drugs to penicillin in the treatment of actinomycosis. In contrast, in vitro resistance (MICs greater than or equal to 4.0 mug/ml) of the pathogenic actinomycetes to metronidazole and tinidazole implies that these drugs may not be valuable in the therapy of human actinomycosis.

Actinomyces↗