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Biomedical subjects

G Potel

Publications and source records attributed to G Potel.

At least 55 records · Page 3Linked to original sources
PubMed1993

Detection of lung and bone infection with anti-granulocyte monoclonal antibody BW 250/183 radiolabelled with 99Tcm.

Twenty-four patients with suspected infection (eight bone, 16 lung) were studied using monoclonal antibody BW250/183 which recognizes epitopes present on the surface of granulocytes. Bronchofibroscopic samples (microbiological studies and alveolar cell counts) were obtained from 14/16 patients with lung disease. Bronchofibroscopy isolated a micro-organism nine times. In two other cases, the diagnosis of infection was based on clinical course data. Infection was confirmed by surgical biopsy in the eight patients with bone pathology. Scans were performed 2 and 24 h after injection of 1 mg BW 250/183 labelled with 99Tcm. For lung disease, immunoscintigraphy was positive six times (five true positive, one false positive) and negative 10 times (six false negative, four true negative). Immunoscintigraphy was false negative when the lung infection was not systematized or no granulocytes were mobilized in the infectious site. Immunoscintigraphy was falsely positive when noninfectious lung disease mobilized granulocytes. It was positive in all patients with bone infection. Images recorded at 24 h had better sensitivity (five false negative) than those at 2 h (eight false negative).

Bone Diseases↗
PubMed1993

Lung distribution and pharmacokinetics of aerosolized tobramycin.

Aminoglycosides are commonly used in the treatment of nosocomial pneumonia in association with beta-lactams. Unfortunately, penetration of intravenously administered aminoglycosides into the lung tissue remains low. In animal models, aerosolization of these drugs provides high lung concentrations and low serum levels. Three-hundred milligrams of tobramycin and 1 ml of 99mTc-DTPA were administered via a pneumatic nebulizer to five healthy volunteers and to five mechanically ventilated patients. Lung scintigraphy was then performed, and plasma and urine pharmacokinetics were studied. In a second group of patients undergoing thoracic surgery, 300 mg of tobramycin alone were administered in the same way; a fragment of healthy lung was then removed, and tobramycin was measured. In the first group, the scintigraphy showed radioactivity distribution in the whole lungs both in healthy volunteers and in ventilated patients. Urine samples contained 5.5% of the initial amount of tobramycin. The mean serum half-life of tobramycin was 8.96 h in healthy volunteers and 11.23 h in ventilated patients. In the second group, mean lung tissue concentrations were 5.5 and 3.61 micrograms/g, respectively, 4 and 12 h after nebulization, respectively. Aerosolization of tobramycin thus produced high lung concentrations and low serum levels.

Aerosols↗
PubMed1992

Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis.

Aminoglycoside bactericidal activity during the first 24 h of treatment probably is a determining parameter in the prognosis of severe gram-negative infections in immunocompromised patients. To identify the predictive factors involved in the definition of the best therapeutic regimen for Enterobacter cloacae and Serratia marcescens infections, we studied different gentamicin, tobramycin, and amikacin regimens by using an experimental model of rabbit endocarditis. Two factors appear to play an important role in predicting in vivo efficacy: (i) the level of in vivo bactericidal activity, which can differ widely from one aminoglycoside to another for the same bacterial strain and from one strain to another of the same species, and (ii) the critical serum drug concentration (CSC, in milligrams per liter), defined as the lowest serum antibiotic concentration capable of producing a significant CFU reduction (P less than 0.05) in endocarditis vegetations 24 h after the beginning of a continuous infusion. Stepwise regression analysis showed that for gentamicin and S. marcescens, the area under the concentration-time curve above the CSC and then the time above the CSC are the determining parameters for efficacy (R = 0.69; F = 13.5; P = 0.001), whereas for amikacin and S. marcescens, the time above the CSC and then the area under the concentration-time curve above the CSC predict efficacy (R = 0.74; F = 24.0; P = 0.0001). The lowest CSC is that of amikacin (about 8 mg/liter); those of gentamicin and tobramycin are about 15 mg/liter. In severe S. marcescens infections, intermittent amikacin dosing offers excellent bactericidal activity within the first 24 h.

Amikacin↗
PubMed1991

Pharmacokinetics of norfloxacin in the elderly.

9 elderly and 9 younger adult patients, with proven post-operative lower urinary tract infection were treated with 400 mg of norfloxacin twice daily for 5 days. Pharmacokinetics of norfloxacin were measured on days 1 and 5. Compared to the younger adult patients, the elderly showed a decreased creatinine clearance and, following the last dose on day 5, an increased maximum plasma concentration of norfloxacin, an increased area under the concentration-time curve and a decreased total body clearance of norfloxacin. These results confirm that in elderly, as in younger adult patients, the pharmacokinetics of norfloxacin can be described by a linear model and accumulation of the drug during repetitive multiple doses is predictable. The differences between the two groups cannot be considered as clinically significant so that no dose change would be required in elderly patients within the range of creatinine clearance studied.

Age Factors↗
PubMed1991

Impact of dosage schedule on the efficacy of gentamicin, tobramycin, or amikacin in an experimental model of Serratia marcescens endocarditis: in vitro-in vivo correlation.

Aminoglycosides are usually considered to be concentration-dependent antibiotics and to have similar pharmacodynamic and pharmacokinetic properties. To verify the equivalent activity of the aminoglycosides on a susceptible strain, we tested the killing rate of three aminoglycosides (gentamicin, tobramycin, and amikacin) on one strain of Serratia marcescens both in vitro and in vivo by using a rabbit model of left-ventricle endocarditis. Despite, similar MICs, the time-kill curve of gentamicin was consistently better than those of amikacin and tobramycin, whatever the concentration of each antibiotic used (1, 2, 4, 8, 16, or 32 mg/liter), after a 5-h incubation. The in vivo bacterial reduction in the vegetations was measured 24 h after administration of an intravenous 48-mg/kg bolus of each antibiotic or at the end of a 24-h continuous intravenous infusion of the same dose. Gentamicin was significantly more effective when administered as a bolus than when administered as a continuous infusion (2.8 +/- 0.2 versus 6.4 +/- 1.5 log10 CFU/g of vegetation, respectively; P less than 0.01), whereas amikacin was more effective as a continuous infusion than as a bolus injection (3.6 +/- 2.0 versus 7.5 +/- 1.3 log10 CFU/g of vegetation, respectively; P less than 0.01). Tobramycin was not very effective, whatever the dosage tested (approximately 6.5 to 7 log10 CFU/g). These results suggest that concentration-dependent bactericidal activities, both in vitro and in vivo, may vary greatly among aminoglycosides despite similar MICs.

Amikacin↗
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

[Fixation of Indium111-labeled antifibrin monoclonal antibody on the vegetation in endocarditis: evaluation in a rabbit model].

The uptake of a 111In labelled antifibrin antibody was studied in left ventricle endocarditis on a rabbit model. The immunospecificity of the antibody for the cardiac vegetations is favorable, exhibiting an uptake at least 4 times that of blood, or myocardium. A planar scintigraphy of the opened left ventricle showed a radionuclide imaging of vegetations, according to anatomical lesions. The use of antifibrin monoclonal antibodies could prove helpful to improve the specificity of valvular lesions visualized by echocardiography, or to detect the small vegetations at the early stage of acute endocarditis.

Animals↗
PubMed1990

Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta-lactamase.

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Animals↗
PubMed1990

Pharmacokinetics of teicoplanin in burn patients.

The pharmacokinetics of teicoplanin were studied in 21 adult burn patients and in 5 healthy controls. All subjects were given a single dose of teicoplanin, 10 mg/kg i.v. The pharmacokinetic parameters of teicoplanin were calculated using a tri-exponential model. Three parameters were investigated--burn surface area, creatinine clearance and time of administration after injury (3 days, 8-10 days and 15-20 days respectively). The elimination half-life was not significantly different between the control group (47 +/- 6 hours), the group with a burn surface area greater than 40% (64 +/- 38 hours), and the group with a burn surface area of 25-30% (44 +/- 15 hours). Trough serum concentrations at 12 hours were consistently less than 8 mg/l in all groups. There was some degree of correlation between creatinine clearance and renal clearance of teicoplanin (p = 0.03; r = 0.44). However, there was no correlation between burn surface area and creatinine clearance, or between the time of administration and creatinine clearance. Non-renal clearance of teicoplanin was unaffected by a large burn surface area. The conclusions from this study are as follows. Burn surface area and time of administration after injury are not predictive factors for the determination of an appropriate dose regimen. Trough serum concentrations at 12 hours emphasize the need for a further intravenous bolus. Burn patients with a high creatinine clearance (greater than 140 ml/min) should be carefully monitored.

Adult↗
PubMed1989

Ceftriaxone-netilmicin combination in single-daily-dose treatment of experimental Escherichia coli endocarditis.

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.

Animals↗
PubMed1989

Pharmacokinetics of fosfomycin in normal and burn patients. Effect of probenecid.

The pharmacokinetics of fosfomycin are modified in burn patients, suggesting a net tubular secretion in such patients. In an attempt to verify this hypothesis, five healthy normal volunteers were studied The pharmacokinetics of fosfomycin were studied with and without probenecid. In the absence of probenecid, the renal clearance of the drug was equal to that of creatinine. With probenecid, the renal clearance of fosfomycin decreased, whereas creatinine clearance did not. This result suggests the existence of a tubular secretion, which might be enhanced in burn patients.

Adult↗
PubMed1988

[Ceftazidime and probabilistic treatment of severe infections in adults].

Probability antibiotic treatments are based on two "best guesses": the nature of the responsible organism and its resistance phenotype. Such treatments are justified in immunocompetent patients with severe infection. The microbiological and pharmacokinetic properties of third generation cephalosporins, and notably ceftazidime, are such that their use as single or combined therapy can be determined. A very wide spectrum and a tendency towards a stronger bactericidal effect are in favour of monotherapy preceded by a short course of bitherapy, especially in cases of hospital-acquired infections.

Adult↗
PubMed1988

[Efficacy of teicoplanin in 25 cases of severe infections caused by gram-positive cocci].

Teicoplanin was evaluated in 25 severe infections caused by Gram-positive bacteria alone [13], in combination [9], alone then in combination [3], in an open study. Of 22 infections that could be evaluated, there were 18 cures and improvements (81.8%), 2 recurrence and 2 failures. Serum concentrations are unpredictable and steady after 5 days i.v. teicoplanin. Trough and peak concentrations are respectively less than 5 mg/l and less than 20 mg/l in 13 infections and higher in 9, unrelated with success or failure. A trough concentration greater than CMI and kind of infection seem deciding. The choice of the antibiotic combined with teicoplanin warrant more data.

Adolescent↗
PubMed1988

[Experimental Enterobacter cloacae endocarditis treated with gentamicin. Predictive value of the in vitro bactericidal rate].

The predictive value of in vitro time-kill curve was tested on an Enterobacter cloacae endocarditis experimental model. The antibiotic studied was gentamicin. Despite a similar MIC, 2 Enterobacter cloacae strains exhibited very different time-kill curves in vitro. This difference was found being predictive of efficacy on the in vivo model, 24 hours after a single injection of gentamicin.

Animals↗
PubMed1987

A reappraisal of norepinephrine therapy in human septic shock.

The effectiveness and safety of iv infused norepinephrine (0.5 to 1 microgram/kg X min) were evaluated in 12 hyperdynamic vasodilated septic patients, who remained hypotensive despite iv volume expansion and antimicrobial and dopamine therapy. During norepinephrine infusion, mean arterial pressure and systemic vascular resistance index increased (p less than .001) and heart rate decreased (p less than .02). Cardiac index either increased or was unchanged in ten patients and decreased slightly in the remaining two patients. Urine flow increased (p less than .01) and was more than 0.5 ml/min when a critical renal perfusion pressure was reached if renal damage was not overwhelming. We conclude that norepinephrine may improve arterial BP and urine flow when volume replacement and dopamine therapy have failed to reverse the hypotension of septic shock.

Adult↗
PubMed1987

Hemodynamic effects of continuous norepinephrine infusion in dogs with and without hyperkinetic endotoxic shock.

We compared, at constant preload maintained by polygeline (gelatin) infusion, the hemodynamic effects of continuous infusion of norepinephrine (0.5, 1, and 1.5 micrograms/kg X min) in anesthetized dogs with and without hyperdynamic endotoxic shock. In both groups, norepinephrine infusion increased systolic, diastolic and mean aortic BP, cardiac index, stroke index, index of myocardial contractility, and mean pulmonary artery pressure. No significant change in right atrial pressure, left ventricular end-diastolic pressure, heart rate, systemic vascular resistance, or pulmonary vascular resistance was observed. Oxygen consumption index and oxygen extraction ratio remained unchanged. Increases in systolic aortic BP were dose-related, whereas maximal effects on other variables were obtained at 0.5 to 1 microgram/kg X min. The rise in aortic pressure resulted from an increased cardiac index but not from an increased systemic vascular resistance. Stroke index increased as contractility improved. The slight alpha-adrenergic effect of continuous, low-dose norepinephrine infusion did not impede the beneficial effects of the marked beta-adrenergic stimulation on cardiac function. The combination of these two effects improved hemodynamic disturbances of hyperdynamic endotoxic canine shock.

Animals↗
PubMed1987

[Pharmacokinetics of pefloxacin in burn patients].

The aim of this study was to evaluate pharmacokinetics of pefloxacin (PFL) in burn patients (n = 11), compared with 5 non burned subjects. The role of the extent of the burn and the delay after initial thermal trauma were also evaluated. Our results suggest that neither the extent of the burn, nor the delay of the study play a role. Compared with non-burned subjects, burn patients exhibit a shorter elimination half-life, but modifications in dosage regimen are not required.

Adult↗