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Biomedical subjects

C Carbon

Publications and source records attributed to C Carbon.

At least 199 records · Page 11Linked to original sources
PubMed1992

Tissue distribution and antifungal effect of liposomal itraconazole in experimental cryptococcosis and pulmonary aspergillosis.

We studied the tissue distribution and in vivo antifungal effect of itraconazole, incorporated into pure dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes and administered intravenously. Eighty percent of the itraconazole was associated with DPPC. Drug levels in lung, brain, and liver, obtained after intravenous administration of tritiated itraconazole, were higher when the drug was administered intravenously as liposomal than when it was dissolved in cyclodextrin. Administration of the liposomal formulation also led to higher and sustained levels of intact itraconazole in serum. Efficacy was assessed in DBA/2 mice infected intravenously with 3 x 10(6) Cryptococcus neoformans, an inoculum responsible for early fatal pneumonia, or 3 x 10(5) C. neoformans, leading to delayed meningitis. In pneumonia, 20 mg/kg of liposomal itraconazole was more effective on survival than the same dose given intravenously in cyclodextrin or twice the dose administered orally dissolved in polyethylene glycol 200. In meningitis, liposomal itraconazole was also more efficient than the drug dissolved in cyclodextrin. These results were confirmed by colony counts in the brain and lung of infected mice. In immunosuppressed OF1 mice infected after inhalation of Aspergillus fumigatus spores, liposomal itraconazole (20 mg/kg x 3) was the only effective treatment. We conclude that intravenous liposomal delivery of itraconazole enhances both concentrations in infected tissues and the in vivo efficacy of the drug. Such passive targeting of antifungal agents other than amphotericin B might be helpful in the treatment of severe systemic mycoses, especially in the case of lung or brain involvement.

Animals↗
PubMed1992

Methods for clinical assessment of expectorants: a critical review.

The purpose of the paper is to discuss some aspects of the methods that are most appropriate for the clinical assessment of new expectorants. Expectorants are drugs devised to help in the removal of bronchial secretions. The evaluation of these drugs is aimed at demonstrating, in controlled trials, their efficacy, safety and, if possible, mechanism of action. Unfortunately, there is no universally accepted assessment technique available. Evaluation of symptoms with the use of self-reported measures is imprecise. Studies of quality of life can assist as a means of assessing the usefulness of this class of drug for patients. Lung function tests evaluate only the possible indirect effects of expectorants; the changes observed are often minor and they do not correlate with other methods of evaluation. Mucociliary clearance studies evaluate bronchial drainage by mucociliary transport and cough. They are a useful pharmacological approach but they cannot replace therapeutic trials. In vitro and ex vivo studies of bronchial secretion, while improving knowledge of the mechanisms of bronchial secretion, fail to predict the modifications of bronchial drainage produced in vivo by cough or mucociliary transport. To be considered efficient, expectorants should not only ease the removal of bronchial secretions, but also improve the patient's condition for the duration of treatment.

Animals↗
PubMed1991

Ascites revealing peritoneal and hepatic extramedullary hematopoiesis with peliosis in agnogenic myeloid metaplasia: case report and review of the literature.

A 61-year-old man presented with ascites in the course of agnogenic myeloid metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia. Subsequently, portal hypertension was demonstrated by hepatic transjugular catheterization. Complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock. A review of the literature and an analysis of mechanisms of ascites occurring in AMM, especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders, are presented.

Adult↗
PubMed1991

Triple-combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a moderately penicillin- and highly glycopeptide-resistant isolate of Enterococcus faecium.

An in vitro bacteriostatic synergy between beta-lactam and glycopeptide antibiotics has been recently described against isolates of Enterococcus faecium moderately resistant to penicillin and highly resistant to vancomycin. The relevance of this synergy in a rabbit endocarditis model was evaluated. Penicillin was tested at low- (LoD) and high-dose (HiD) regimens, alone or combined with vancomycin and/or gentamicin. Compared with controls, after a 5-day treatment: LoD penicillin, vancomycin, gentamicin, LoD penicillin plus gentamicin or vancomycin, and vancomycin-gentamicin were not effective; LoD penicillin-vancomycin caused a small reduction of bacterial titers in vegetations that was strongly enhanced by adding gentamicin; HiD penicillin-gentamicin, the most effective regimen, was not significantly better than LoD penicillin-vancomycin-gentamicin. These results suggest that the relative in vivo inefficacy of penicillin-vancomycin might be related to the fact that this combination was poorly bactericidal, and the triple combination of LoD penicillin-vancomycin-gentamicin or the combination of HiD penicillin-gentamicin should be considered in the treatment of serious infections due to beta-lactam- and glycopeptide-resistant enterococci.

Animals↗
PubMed1991

Reappraisal of amoxycillin absorption kinetics.

Interest in the intestinal absorption mechanisms of drugs has increased because transepithelial passage across the gut does not necessarily follow a passive diffusion process. Amoxycillin, like other amino-beta-lactam antibiotics, has been demonstrated in vitro to use the dipeptide carrier-mediated system in rodent small intestine. In order to assess the in-vivo relevance of these data, we applied the Loo-Riegelman method for a reappraisal of amoxycillin absorption kinetics in healthy human volunteers. The results showed evidence of a saturable carrier-mediated uptake of this antibiotic. With respect to the in-vitro data previously published, the dipeptide carrier system would appear to be the most likely transport mechanism.

Administration, Oral↗
PubMed1991

Ceftriaxone diffusion into cardiac fibrin vegetation. Qualitative and quantitative evaluation by autoradiography.

Heterogeneous diffusion of some antibiotics into fibrin rich infectious processes is one explanation of the difficulty to cure infections such as endocarditis. Ceftriaxone is a beta lactam antibiotic, potentially useful due to a broad spectrum of activity and its long elimination half-life. We investigated by means of autoradiography the diffusion of labelled ceftriaxone into large infected cardiac vegetations obtained in a rabbit model of endocarditis. Ten d after infection 250 microCi 14C ceftriaxone was injected over 30 min. Thirty min after the end of infusion (T30) vegetation/blood radioactivity ratio was 0.58 +/- 0.4 (n = 3). At T200, radioactivity decreased approximatively 3-fold, in blood and in vegetations simultaneously. Autoradiography showed that at T30, ceftriaxone was 20-30 times more concentrated at the periphery of vegetation than in the core. Autoradiography obtained at T200 showed a progressive diffusion toward the core. The diffusion gradient may explain the fact that high local concentrations are necessary to sterilize vegetations. The pattern of diffusion of antibiotics in fibrin is an important pharmacokinetic parameter for predicting in vivo activity.

Animals↗
PubMed1991

Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding.

The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.

Animals↗
PubMed1991

Endotoxin-tobramycin additive toxicity on renal proximal tubular cells in culture.

Aminoglycoside-induced renal damage is enhanced in animals with Escherichia coli pyelonephritis. Bacterial endotoxin is liberated during antibiotic therapy. The toxic effect of endotoxin and tobramycin, alone or in combination, was investigated in primary cultures of rabbit proximal tubular cells grown to confluence in serum-free medium. Sodium-dependent uptakes of Pi and alpha-methylglucopyranoside (MGP) and enzymatic activities (lactate dehydrogenase [LDH] released as a marker of cell necrosis and gamma-glutamyltransferase [GGT] and N-acetyl-beta-D-glucosaminidase [NAG] present in the homogenate as markers of brush border membrane and lysosome integrity) were measured. Cells were exposed to (i) endotoxin (20 mg/liter), tobramycin (1 mM), or endotoxin plus tobramycin for 48 h, or (ii) endotoxin (100 mg/liter), tobramycin (4 mM), or endotoxin plus tobramycin for 72 h. Endotoxin alone did not alter Pi uptake, but tobramycin inhibited Pi uptake through a decrease in Vmax. The effect was not enhanced by the combination of endotoxin and tobramycin. Endotoxin and tobramycin alone exerted no significant effect upon MGP uptake, but strong inhibition of the Vmax was observed after exposure to a combination of endotoxin plus tobramycin, without alteration of the Km. Endotoxin decreased residual GGT activity in the cell homogenate. Tobramycin increased LDH release in the medium and NAG activity in the homogenate. Endotoxin plus tobramycin resulted in an additive effect upon LDH and NAG activities. In conclusion, by disturbing apical membrane integrity, endotoxin increased tobramycin toxicity in vitro in the absence of serum hormonal mediator.

Acetylglucosaminidase↗
PubMed1991

Limited protection by small unilamellar liposomes against the renal tubular toxicity induced by repeated amphotericin B infusions in rats.

Amphotericin B (AMB), either alone or incorporated into small unilamellar vesicles of pure dipalmitoylphosphatidyl choline (DPPC SUV-AMB), was administered intravenously to male Sprague-Dawley rats once daily for 5 days. Either 1.5 or 3.5 mg of AMB or DPPC SUV-AMB per kg was given, since these concentrations corresponded, respectively, to the lowest nephrotoxic dose and the sublethal dose of AMB in our model. Tubular functions were evaluated daily, and AMB concentrations in plasma, urine, and tissues were measured by high-performance liquid chromatography. AMB at both doses induced tubular toxicity, hyposthenuria being the earliest symptom. DPPC SUV-AMB at 1.5 mg/kg/day was atoxic, but the tubular alterations induced by 3.5 mg of DPPC SUV-AMB per kg were similar to those observed with 3.5 mg of AMB per kg, except that the ability to concentrate urine was partly restored 72 h after the last infusion. Incorporating AMB into DPPC SUV did not influence the pharmacokinetics of the drug. Using this lipidic AMB formulation, we thus observed a beneficial effect toward limiting the renal tubular toxicity of repeated low doses of AMB but, unexpectedly, not that of high doses. These results indicate that tubular renal functions and electrolyte serum values should be closely monitored in patients treated with AMB liposomal formulations, especially high-dose regimens.

Acetylglucosamine↗
PubMed1991

Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.

Animals↗
PubMed1990

[Evaluation of the reagent strip method to detect urinary tract infections. In hospital patients].

Asymptomatic urinary tract infections (UTI) are frequent in hospital patients. Two prospective studies were carried out to evaluate the reagent strip method used to detect these infections. The diagnosis of UTI rested on cytobacteriological examination of urine. Detection by reagent strip was performed either in the microbiology laboratory (study 1:976 samples) or at the patient's bedside and in the laboratory (Study 2:312 samples). The strips were examined visually and by an automated device. There was no significant difference between the results obtained with these two reading methods. Study 1 showed that the reagent strip is more useful to exclude the diagnosis of UTI by using the leucocyte zone alone or combined with the nitrite zone (negative predictive value 98 percent) than to assert this diagnosis. Study 2 showed that the nitrite zone was less sensitive when it was examined at the laboratory than at the patient's bedside. Analysis of discordances between reagent strip and cytobacteriology in the light of data supplied by the patient's medical records made it possible to improve the negative predictive value of the tests. (100 percent). Thus, 60 percent of cytobacteriological examinations might be avoided if this type of examination was performed only in urine with positive leucocyte or nitrite zones. This means a 15 percent saving in B-coded examinations performed in hospital microbiology laboratories.

Hospitals↗
PubMed1990

[Evaluation of the detection of urinary tract infection by the reagent strip method in hospitalized patients].

Asymptomatic urinary tract infections (UTI) are frequent in hospital patients. Two prospective studies were carried out to evaluate the reagent strip method used to detect these infections. The diagnosis of UTI rested on cytobacteriological examination of urine. Detection by reagent strip was performed either in the microbiology laboratory (study 1: 976 samples) or at the patient's bedside and in the laboratory (Study 2: 225 samples). The strips were examined visually and by an automated device. There was no significant difference between the results obtained with these two reading methods. Study 1 showed that the reagent strip is more useful to exclude the diagnosis of UTI by using the leucocyte zone alone or combined with the nitrite zone (negative predictive value 98 percent) than to assert this diagnosis. Study 2 showed that the nitrite zone was less sensitive when it was examined at the laboratory than at the patient's bedside. Analysis of discordances between reagent strip and cytobacteriology in the light of data supplied by the patient's medical records made it possible to improve the negative predictive value of the tests. (100 percent). Thus, 60 percent of cytobacteriological examinations could be avoided if this type of examination was performed only in urine with positive leucocyte and nitrite zones. This means a 15 percent saving in B-coded examinations performed in hospital microbiology laboratories.

France↗
PubMed1990

In vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination against Listeria monocytogenes.

The in vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination was determined against seven strains of Listeria monocytogenes by the killing curve method. Amoxicillin plus gentamicin was the most rapidly bactericidal combination, whereas trimethoprim-sulfamethoxazole was less bactericidal at 6 h but as bactericidal at 24 h. The combination of trimethoprim-sulfamethoxazole with either amoxicillin, ciprofloxacin or rifampicin did not result in antagonism, but the combinations were no more active than trimethoprim-sulfamethoxazole alone. The interaction of amoxicillin with rifampin was fairly antagonistic (1 log10 difference). The combination of amoxicillin and ciprofloxacin, although producing antagonism during the first 6 h, was more active at 24 h than amoxicillin alone and prevented the regrowth observed with ciprofloxacin alone. Ciprofloxacin and rifampicin interacted antagonistically during the first 6 h, and the combination was not very bactericidal (3 log10) but prevented the emergence of mutants, as observed with each drug alone, when used at concentrations greater than the MICs for the strain tested. These regimens merit evaluation in in vivo models of Listeria monocytogenes meningitis.

Anti-Bacterial Agents↗