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Biomedical subjects

C Edlund

Publications and source records attributed to C Edlund.

At least 91 records · Page 5Linked to original sources

Ciprofloxacin concentrations and impact of the colon microflora in patients undergoing colorectal surgery.

Ciprofloxacin was given perorally in two doses of 750 mg each with a 12-h interval starting 24 h prior to surgery, 400 mg of ciprofloxacin was given intravenously at the induction of anesthesia, and 400 mg of ciprofloxacin was given 12 h later to 21 patients undergoing elective colorectal surgery. The maximum concentrations in serum (mean value +/- standard deviation, 11.1 +/- 7.8 mg/liter) during surgery were reached 30 min after ciprofloxacin was administered. The ciprofloxacin concentrations in the intestinal mucosa samples were 2.7 to 37.8 mg/kg of tissue weight, and the concentrations in the fecal samples were less than 0.1 to 858 mg/kg. The aerobic and anaerobic bacteria in the fecal flora were suppressed markedly during the prophylaxis period. No postoperative infections occurred.

Adult↗

Influence of ciprofloxacin on the colonic microflora in young and elderly volunteers: no impact of the altered drug absorption.

The colonic microflora was studied before, on the fifth day of dosing, and 2 weeks after a 5-day oral course of ciprofloxacin 500 mg BID given to 7 young and 7 elderly, healthy volunteers. Considerable changes in the aerobic microflora were found, while the effects on the anaerobic bacteria were less pronounced. Despite larger absolute bioavailability of the first dose in the elderly (77 vs. 63%; p less than 0.05), the effect of ciprofloxacin on the microflora was similar in the two groups of volunteers. A higher number of clostridia were detected in faeces from elderly subjects before, during, and after the ciprofloxacin regimen.

Administration, Oral↗

Ecological impact of antimicrobial prophylaxis on intestinal microflora in patients undergoing colorectal surgery.

During recent years the impact of different antimicrobial agents on the intestinal microflora in patients undergoing colorectal surgery has been investigated by our research group. Thus the effects on the microflora by parenteral administration of piperacillin, cefoxitin, cefbuperazone, moxalactam, aztreonam, imipenem, ampicillin + sulbactam, clindamycin, tinidazole, ciprofloxacin and ofloxacin have been studied. Pronounced changes were observed in the aerobic microflora in patients receiving ciprofloxacin and ofloxacin, in the anaerobic microflora in patients receiving clindamycin and tinidazole and in both the aerobic and anaerobic microflora in those patients receiving piperacillin, cefoxitin, cefbuperazone, moxalactam, aztreonam, imipenem and ampicillin + sulbactam. Postoperative infections were observed in patients receiving piperacillin (2), ampicillin + sulbactam (1), cefoxitin (1), aztreonam (3), tinidazole (6), clindamycin (5) and ofloxacin (5). In the patient groups receiving cefbuperazone, moxalactam, imipenem and ciprofloxacin, no postoperative infections occurred.

4-Quinolones↗

Clinical impact of newer quinolones: influence on normal microflora.

This review article summarizes the published data concerning the impact of ciprofloxacin and norfloxacin on the oropharyngeal and intestinal human microflora. The use of ciprofloxacin and norfloxacin for selective decontamination in compromised patients and for prophylaxis of recurrent urinary tract infections is also reviewed.

Bacterial Infections↗

Suppression of the oropharyngeal and gastrointestinal microflora by ciprofloxacin: microbiological and clinical consequences.

The impact of ciprofloxacin on the human oropharyngeal and gastrointestinal microflora has been studied by several authors during the last years. The use of ciprofloxacin for selective decontamination in immunocompromised patients has also been investigated. This review article summarizes the published data concerning these studies. The results show that the impact on the oropharyngeal microflora is minor. Administration of ciprofloxacin leads to a rapid elimination of the major components of the aerobic Gram-negative intestinal microflora. The aerobic Gram-positive flora is partly affected, while the impact on the anaerobic microorganism is minor. Oral ciprofloxacin given prophylactically to immunocompromised patients during severe granulocytopenia prevented colonization with potentially pathogenic aerobic Gram-negative rods, and reduced the incidence of infections caused by these microorganisms. There was no effect on the incidence of aerobic Gram-positive or fungal infections. Administration of ciprofloxacin seems not to predispose to the development of resistant microorganisms.

Bacteria↗

The half-lives of dolichol and dolichyl phosphate in rat liver.

Rat liver dolichol and dolichyl-P were labeled by injection of [3H]mevalonate into the portal vein and their rates of synthesis and breakdown determined. In the initial phase the radioactivity appeared in alpha-unsaturated polyprenols. Subsequent saturation required 90 min. The half-lives of dolichols in microsomes were between 80 and 118 h, and shorter dolichols had shorter values of T1/2. The half-lives of dolichols in lysosomes were between 115 and 137 h, while microsomal dolichyl-P exhibited a T1/2 of 32 h. Injected dolichol was recovered in the lysosomes of hepatocytes and exhibited a rate of breakdown which was slower than that of the endogenous compound. These results indicate differences in the catabolism of dolichol at different subcellular locations, as well as differences between the catabolism of dolichol and dolichyl-P.

Animals↗

Impact of Lactobacillus acidophilus on the normal intestinal microflora after administration of two antimicrobial agents.

Twenty healthy volunteers participated in a comparative study concerning the influence of Lactobacillus acidophilus supplements on the normal intestinal microflora after the administration of two antimicrobial agents, enoxacin and clindamycin, respectively. L. acidophilus NCFB 1748 was given as a fermented milk product containing 5 x 10(8)-2 x 10(9) CFU/ml to ten of the volunteers immediately after the administration of the antimicrobial agents. On the seventh day of enoxacin administration enterobacteria were eliminated in nine of ten subjects. Enterococci disappeared or decreased significantly in five subjects. During the L. acidophilus supplementation, there was a significant increase in the number of Escherichia coli in one subject, while enterococci returned to the same level as before enoxacin administration in all subjects.

Adult↗

A review on the impact of 4-quinolones on the normal oropharyngeal and intestinal human microflora.

During the last few years the impact of the newer 4-quinolones, ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin, on the human microflora has been studied by several investigators. This review article summarizes the published data concerning these studies. The results show that the oropharyngeal flora is affected only slightly or not at all by the 4-quinolones. All the newer 4-quinolones have a similar effect on the normal intestinal flora. The gram-negative aerobic flora is strongly suppressed during administration of 4-quinolones, while the gram-positive flora is only slightly affected. The anaerobic microflora is hardly affected at all. The emergence of resistant bacterial strains is uncommon, although one study shows increased MIC-values for anaerobes during ciprofloxacin administration. Replacement by yeasts or other inherently resistant microorganisms does not often seem to be a problem. High concentrations of the 4-quinolones are reached in faeces, values between 100-2,200 mg/kg being reported. Since the 4-quinolones do not cause marked ecological disturbances in the intestinal microflora, they may be suitable for selective decontamination in immunocompromised patients, for prophylaxis of urinary tract infections and for treatment of bacterial intestinal infections.

Ciprofloxacin↗

Effect of ofloxacin on oral and gastrointestinal microflora in patients undergoing gastric surgery.

The effect of ofloxacin on the microflora in saliva, gastric juice, and feces was evaluated in 24 patients undergoing gastric surgery. A single peroral dose of 400 mg ofloxacin was given to each patient 2-4 h before surgery. The concentrations of ofloxacin in serum, saliva, gastric juice, and gastric mucosa tissue were assayed. Only Branhamella cocci were affected in the saliva. In the gastric juice, both the aerobic and anaerobic flora were suppressed on the day of surgery, but increased in number afterwards. There was a significant correlation between gastric pH and the number of microorganisms isolated in the gastric juice on day 0. In faeces, the aerobic and part of the anaerobic flora were suppressed by the administration of ofloxacin. Ofloxacin was well tolerated by the patients. Four of 24 patients developed postoperative complications. Microorganisms isolated from wound sepsis and intraabdominal sepsis (three patients) were Staphylococcus epidermidis, Staphylococcus aureus, hemolytic streptococci group A, Streptococcus sp. and Escherichia coli. All related infections occurred in patients with very low ofloxacin serum concentrations, probably due to impaired absorption. Oral antibiotic prophylaxis is not recommended in patients in whom impaired gastric emptying can be expected.

Adult↗

Norfloxacin binds to human fecal material.

Earlier studies have reported very high (120 to 2,700 mg/kg) concentrations of norfloxacin in feces after therapeutic doses. MICs for fecal microorganisms are with few exceptions far below these levels. Nevertheless, clinical investigations show that the main part of the aerobic gram-positive and the anaerobic microflora remains unaffected after norfloxacin administration. In this study, the binding of [14C]norfloxacin to fecal material was analyzed. The binding of a group of nonlabeled quinolones to feces and the interactions between Enterococcus faecium, Bacteroides fragilis, and norfloxacin were also investigated. The results showed that norfloxacin has the ability to bind to feces. The specific binding was reversible, saturated after 90 min of incubation at 37 degrees C, and increased linearly with fecal concentration. Scatchard plots and nonlinear regression computer analyses revealed two different binding classes. The primary specific binding had a dissociation constant (KD) of 1.0 microM and a maximal binding capacity (Bmax) of 0.12 mumol/g of feces. The KD and Bmax of the secondary, more unspecific binding were 450 microM and 11.8 mumol/g of feces, respectively. The binding of unlabeled ciprofloxacin, enoxacin, ofloxacin, pefloxacin, and norfloxacin to feces was comparable to that of [14C]norfloxacin. The results of norfloxacin binding to suspensions of B. fragilis suggested that the main part of the binding is to the bacterial fraction of feces. In the presence of 8.0 g (dry weight) of B. fragilis per liter, the MBC of norfloxacin for E. faecium increased from 8 to 256 micrograms/ml. The finding of the present study indicated that binding of norfloxacin to feces may explain the paradox of high fecal concentrations of norfloxacin versus the actual effect on the normal gastrointestinal microflora.

Adult↗

Manipulation of the oropharyngeal and intestinal microflora by norfloxacin: microbiological and clinical aspects.

During the last few years the impact on the human endogenous microflora by norfloxacin has been studied by several investigators. The use of norfloxacin for selective decontamination in compromised patients and for prophylaxis of recurrent urinary tract infections has also been investigated. This review article summarizes the published data from these studies. The results show that the oropharyngeal flora is only slightly affected by norfloxacin. In the intestinal flora, the Gram-negative aerobic microorganisms are strongly suppressed during administration of norfloxacin. The impact on the Gram-positive aerobic flora is minor, while the anaerobic intestinal microflora is virtually unaffected by the administration. In two studies where norfloxacin was given prophylactically to granulocytopenic patients, the development of aerobic Gram-negative infections was suppressed and overall morbidity decreased. Norfloxacin for long-term prophylaxis of infections in artificially ventilated patients in intensive care units was reported to give encouraging results in one investigation. Two studies indicated that long-term norfloxacin prophylaxis reduces the rate of recurrent urinary tract infections. Norfloxacin administration seems not to predispose for development of resistance to 4-quinolones nor to other commonly used antimicrobial agents.

Bacteria↗

Effect of enoxacin on colonic microflora of healthy volunteers.

Ten healthy volunteers received 400 mg enoxacin orally twice daily for seven days. Fecal specimens were collected at 0, 2, 4, 7, 9, 11, 16 and 21 days to study the effect of enoxacin on the normal colonic microflora. On the seventh day the fecal mean concentration of enoxacin was 348 mg/kg feces. Whereas enterobacteria were strongly suppressed during the administration of enoxacin, the gram-positive and anaerobic microflora was not significantly altered. Two weeks after enoxacin was discontinued, the colonic microflora had returned to normal.

Adult↗

Changes in hepatic dolichol and dolichyl monophosphate caused by treatment of rats with inducers of the endoplasmic reticulum and peroxisomes and during ontogeny.

Rats were treated with various inducers of the endoplasmic reticulum and peroxisomes and the properties and distributions of dolichol and dolichyl phosphate analyzed. The treatment of rats with carcinogenic agents 2-acetylaminofluorene, N-nitrosodiethylamine and 3-methylcholanthrene and with the compounds such as phenobarbital, terpentine, cholestyramine and di(2-ethylhexyl)phthalate have all caused changes in the microsomal or lysosomal contents of dolichol to various extents, but only the latter group influenced dolichyl-P concentration. Shortly after birth, the hepatic content of dolichyl-P reaches the adult level, whereas the level of the free alcohol is low at birth but increases continuously thereafter. Incorporation of [3H]mevalonate into dolichol was also dependent on factors other than de novo synthesis, e.g., the pool size. Rates of glycosylation reactions dependent on dolichyl-P exhibit considerable changes but are independent of the existing levels of lipid intermediate. GDP-mannosyl transferase activity increases greatly with birth, but the enzyme activity returns to the adult level within a day after birth. These results demonstrate that structural and functional modifications induced with drugs can greatly influence the content and distribution of dolichol which are independent of the existing levels of dolichyl-P.

2-Acetylaminofluorene↗

Comparative effects of enoxacin and norfloxacin on human colonic microflora.

Ten healthy volunteers received 400 mg of enoxacin and another ten healthy volunteers received 200 mg of norfloxacin orally twice a day for 7 days. Fecal specimens were collected before, during, and after drug administration to study the impact of enoxacin and norfloxacin on the normal colonic microflora. On day 7, the mean concentrations of enoxacin and norfloxacin were 350 and 950 mg/kg of feces, respectively. Enoxacin and norfloxacin affected the colonic microflora in similar ways. The number of strains of the family Enterobacteriaceae was markedly suppressed during drug administration, whereas the gram-positive and anaerobic microfloras were not significantly altered. Two weeks after withdrawal of the drugs, the colonic microflora had returned to normal.

Adult↗

Effects of prolonged administration of phthalate ester on the liver.

Di(2-ethylhexyl)phthalate (DEHP) was administered to male rats in the diet at concentrations of 2.0, 0.2, and 0.02% for up to 102 weeks. Low doses resulted in moderate increases in certain hepatic enzymes during the initial phase of exposure and in a continuous increase in the activities of these same enzymes throughout the treatment period. An increased level of dolichol and decreased concentration of dolichyl-P were observed. Furthermore, the rate of protein glycosylation diminished. Liver biopsies from patients subjected to hemodialysis demonstrated an increased number of peroxisomes. Phthalate ester seems to interfere with protein turnover, so that the half-life of total mitochondrial and microsomal protein is considerably increased.

Acyl-CoA Dehydrogenase↗

Effect of norfloxacin on human oropharyngeal and colonic microflora and multiple-dose pharmacokinetics.

10 healthy volunteers received 200 mg norfloxacin orally every 12 h for 7 days. Saliva, throat and faecal specimens were collected days 0, 3, 5, 7, 14 and 21 to study the effect of norfloxacin on the normal microflora. The concentrations of norfloxacin in serum, urine, saliva and faeces were determined by a microbiological method and all samples except faeces were also assayed by high-pressure liquid chromatography (HPLC). The pharmacokinetics of norfloxacin were studied on day 3. The mean peak serum concentration (+/- SD) attained after 0.75-1.0 h was 0.75 +/- 0.15 mg/l measured by HPLC, and the mean terminal serum half-life was 4.2 +/- 0.6 h. The mean cumulative urinary elimination was 29% during 12 h after dosing. There was no significant difference between values obtained by microbiological assay and by HPLC. The saliva concentration was approximately 30% of the serum levels 1.0-1.5 h after administration. No accumulation in faeces was found during the administration period, and mean concentrations were 940 mg/kg. The changes in the oropharyngeal flora were minor and only branhamella were affected. In the colonic flora, the number of enterobacteria was strongly depressed while the anaerobic microflora was only slightly affected. Two weeks after the administration period, both the oropharyngeal and colonic microflora had returned to normal.

Adult↗

The influence of prolonged di(2-ethylhexyl)phthalate treatment on the dolichol and dolichyl-P content of rat liver.

Dolichols and glycosyl transferase activities were studied in rat liver fractions after treatment with the plasticizer di(2-ethylhexyl)phthalate, an inducer of peroxisomes and mitochondria. After a few weeks of treatment with 2% plasticizer in the diet, the amount of dolichol is more than doubled in the lysosomes but not in the microsomes while dolichyl-P decreased by 50% in the microsomes but not in the lysosomes. The isoprenoid pattern for dolichol and dolichyl-P, respectively, is modified to longer polyprenols in the two fractions as seen in the percent distribution of the individual isoprenes. Dolichyl-P and protein glycosylation by N-acetylglucosamine and mannose decreased considerably. Incubation with mixtures containing exogenous dolichyl-P did not increase protein glycosylation. Phthalate ester treatment for 2 years increased dolichol content above the control values even when the dose was decreased a hundred times, to 0.02%. The results demonstrate a compartmentalization of dolichol and dolichyl-P distribution, and the induction studies suggest that hepatocytes possess separate regulating mechanisms for these two compounds.

Animals↗