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P Le Conte

Publications and source records attributed to P Le Conte.

At least 19 recordsLinked to original sources
PubMed2005

[CRP in the management of bacterial infections in emergency].

OBJECTIVES: To assess the interest of measuring CRP in emergency for diagnosing bacterial infections and making decisions about antibiotics and to compare its practical usefulness with clinicians' conclusions. METHODS: Systematic CRP measurements in 80 consecutive patients admitted to emergency ward with possible bacterial infection. RESULTS: were not transmitted to the physician in charge. Patients' files were analyzed retrospectively in two phases. In phase 1, two senior physicians assessed the diagnosis and need for antibiotics on the basis of the admission (emergency unit) files. In phase 2, a panel of experts examined the complete files (including discharge notes) to determine the likelihood of infection (obvious or probable, unlikely or excluded) and appropriateness of emergency antibiotics. Their recommendations were used as the standard, against which the usefulness of the laboratory indicators (including CRP) and decisions of the emergency physicians were assessed. ROC curves were used to determine threshold values for CRP and body temperature. We then calculated the sensitivity, positive predictive value and negative predictive value of these cutoffs and compared them with those for the phase 1 clinician recommendations. RESULTS: The study included 76 patients (mean age: 74 years): 28 presented obvious or possible infections and 21 required emergency antibiotic therapy. Mean leukocyte values did not differ between groups. For diagnosis, the threshold value of CRP was 85 mg/L and of body temperature 37.8 degrees C; for prescribing antibiotics, the values were 130 mg/L and 38 degrees C, respectively. The sensitivity, specificity, negative and positive predictive values of CRP were, respectively, 79, 81, 76, and 83% for diagnosis of bacterial infection and 71, 71, 48 and 87% for prescription of an emergency antibiotic. These values were lower than those of clinician's conclusions. CONCLUSION: Because of the variability in the thresholds used in its interpretation, the lack of specificity, and its poor predictive value for treatment decisions, CRP is of little interest in the diagnosis and treatment of patients with bacterial infections in intensive care. The cost generated by this examination is therefore not justified.

Adult↗
PubMed2001

[Acute pyelonephritis. Randomized multicenter double-blind study comparing ciprofloxacin with combined ciprofloxacin and tobramycin].

OBJECTIVES: To investigate the effects of an intravenous injection of tobramycin (T) in female patients with acute uncomplicated pyelonephritis treated with ciprofloxacin (CIP) (500 mg bid per os). METHODS: It was a randomized, multicenter, double-blind study conducted in six departments of emergency medicine. The main exclusion criteria were: previous history of urinary tract malformation of lithiasis, a recent urological procedure, pregnancy, diabetes mellitus, immunodepression, or severe sepsis. The primary criteria for evaluation were: the percentage and rate of clinical recovery, as well as bacteriological efficacy. RESULTS: 118 women were enrolled, 60 in the tobramycin group and 58 in the placebo group. E. coli was the most commonly isolated organism; all organisms were susceptible to ciprofloxacin and tobramycin. Two women in the CIP + T group and four women in the CIP + P group failed to respond clinically. The recovery rate was similar in the two groups (96 and 93% respectively). CONCLUSION: Administration of a dose of tobramycin did not demonstrate its clinical benefit in treatment of acute uncomplicated pyelonephritis treated by oral ciprofloxacin.

Acute Disease↗
PubMed2001

In vivo efficacy of continuous infusion versus intermittent dosing of ceftazidime alone or in combination with amikacin relative to human kinetic profiles in a Pseudomonas aeruginosa rabbit endocarditis model.

Ceftazidime and amikacin were administered in a Pseudomonas aeruginosa rabbit endocarditis model using computer-controlled intravenous (iv) infusion pumps to simulate human serum concentrations for the following regimens: continuous (constant rate) infusion of 4, 6 or 8 g of ceftazidime over 24 h or intermittent dosing of 2 g every 8 h either alone or in combination with amikacin (15 mg/kg once daily). The in vivo activities of these regimens were tested on four Pseudomonas aeruginosa strains. Animals were killed 24 h after the beginning of treatment. Efficacy was assessed by comparing the effects of the different groups on bacterial counts in vegetations for each strain tested. For a susceptible reference strain (ATCC 27853; MICs of ceftazidime and amikacin 1 and 2 mg/L, respectively), continuous infusion of 4 g alone or with amikacin was as effective as intermittent dosing with amikacin. For a clinical isolate producing an oxacillinase (MICs of ceftazidime and amikacin 8 and 32 mg/L, respectively), continuous infusion of 6 g was equivalent to intermittent dosing. For a clinical isolate producing a TEM-2 penicillinase (MIC of ceftazidime and amikacin 4 mg/L), continuous infusion of 6 g, but not intermittent dosing, had a significant in vivo effect. For a clinical isolate producing an inducible, chromosomally encoded cephalosporinase (MIC of ceftazidime and amikacin 8 and 4 mg/L, respectively), neither continuous infusion nor intermittent dosing proved effective. Determination of ceftazidime concentrations in vegetations showed that continuous infusion produced tissue concentrations at the infection site far greater than the MIC throughout the treatment. It is concluded that continuous infusion of the same total daily dose provides significant activity as compared with fractionated infusion. This study confirms that a concentration of 4-5 x MIC is a reasonable therapeutic target in most clinical settings of severe P. aeruginosa infection.

Amikacin↗
PubMed2000

[Administration of tobramycin aerosols in patients with nosocomial pneumonia: a preliminary study].

OBJECTIVE: The aim of this study was to assess renal and respiratory tolerance of aerosolized tobramycin in intubated and mechanically ventilated patients with nosocomial pneumonia. PATIENTS AND METHODS: This was a multicenter, randomized, double-blind, placebo controlled study. Thirty-eight mechanically ventilated patients with documented nosocomial pneumonia were included. Patients treated with intravenous betalactam and tobramycin were randomly allocated to receive aerosolized tobramycin (6 mg/kg/day, n = 21) or placebo (n = 17). The aerosol was administered via a pneumatic nebulizer once a day for 5 days. RESULTS: Respiratory tolerance was good in all but two patients. No acute renal failure occurred. By day 10, 7 patients in the tobramycin group (35%) had been extubated versus 3 in the placebo group (18.5%, p = 0.18). By day 28, 6 patients had died (2 in the tobramycin group and 4 in the placebo group, p = 0.23). CONCLUSION: Aerosolized tobramycin was well tolerated in ventilated patients with documented nosocomial pneumonia.

Adult↗
PubMed1999

Prognostic factors in acute cardiogenic pulmonary edema.

The purpose of this study was to determine the clinical and biological findings at admission in the Department of Emergency Medicine associated with a poor prognosis, and to evaluate early response to treatment as a prognostic factor. It was a prospective cohort study with a 5-month follow-up. One hundred eighty-six patients admitted for acute cardiogenic pulmonary edema were included. Features were analyzed at the admission and on response to initial treatment. The main outcome measure was survival at 2 end-points: hospital discharge, and 5 months of follow-up. Multivariate analysis showed that in-hospital mortality was associated with marbleization (mottling) odd-ratio (OR) = 9.0), low diuresis (OR = 4.0), high breath rate 6 hours after admission (OR = 4.0), and chronic digoxin use (OR = 3.39). Five-month mortality was associated with a bedridden state (OR = 9.0), marbleization (mottling) (OR = 5.5), myocardial infarction (OR = 3), and poor early response to initial treatment (OR = 3.2). In addition to well-known factors, the response to initial treatment evaluated 6 hours after admission was a major determinant of outcome.

Acute Disease↗
PubMed1998

[Diagnostic difficulties of myocardial infarct in an admissions and emergency service: influence of age].

OBJECTIVE: To analyze the clinical signs and electrocardiographic and enzyme data in patients admitted to an emergency ward for myocardial infarction in order to highlight diagnostic pitfalls. PATIENTS AND METHODS: All patients admitted to our emergency ward between October 1995 and October 1996 with elevated myoglobulin or creatinine phosphokinase (CPK) levels (n = 457 patients) were included in the study series. Patient files were randomly selected (n = 257 files) for review by an emergency ward specialist and a cardiologist to identify cases of myocardial infarction (n = 88 patients, mean age 73.4 +/- 15.2 years). Clinical, electrical and enzyme data (including CPK-MB) were analyzed. RESULTS: The patients had been referred for chest pain (69%), dyspnea (24%) or another disorder (7%). Pain was located in the retrosternal area in 51%, in the lower chest in 19% and elsewhere in 30%. Delay between onset of pain and transfer to the emergency ward was 5 h 20 min +/- 6 h. Signs of left heart failure were observed in 50% of the patients. The admission electrocardiogram showed complete criteria for myocardial infarction in 43% of the cases, incomplete criteria in 21% and was non-contributive in 36%. Enzyme results were elevated in 78% of the cases at the first assay and in 98.2% at the second assay. Both typical chest pain and ECG were observed in only 30% of the cases. Chest pain was present in 55% of the patients over 75 years of age and in 81% of those under 75 years (p = 0.007). CONCLUSION: A typical syndrome is observed in less than one-third of all patients with myocardial infarction admitted to emergency wards. The frequency of atypical presentations increases with age.

Age Factors↗
PubMed1997

Bactericidal effect of pefloxacin and fosfomycin against Pseudomonas aeruginosa in a rabbit endocarditis model with pharmacokinetics of pefloxacin in humans simulated in vivo.

The bactericidal activity of pefloxacin and fosfomycin alone and in combination against Pseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4 +/- 11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12-48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.

Animals↗
PubMed1997

Replacement fluids in plasmapheresis: cross-over comparative study.

OBJECTIVE: To compare the tolerance and the cost of three replacement fluids in plasmapheresis: albumin 4% alone, albumin 4% + dextran 40, or albumin 4% + hydroxyethylstarch 6%. DESIGN: A one center randomized, cross-over, comparative study designed to explore the tolerance and the colloid oncotic pressure in patients undergoing plasmapheresis. PATIENTS: 225 plasmapheresis procedures were performed in 27 patients. MEASUREMENTS AND RESULTS: Hemodynamic tolerance was good in the three treatment groups. Serum protein concentration after plasmapheresis was significantly lower in the albumin + hydroxyethylstarch group, followed by albumin + dextran 40, versus albumin alone. Colloid oncotic pressure before and after exchange was similar in the three groups. CONCLUSIONS: The clinical use of 25-30% of hydroxyethylstarch 6% or dextran 40 with albumin 4% was clinically well tolerated and associated with a 12% decrease of the cost of substitution solutions.

Adult↗
PubMed1996

In vivo antibacterial effects of simulated human serum profiles of once-daily versus thrice-daily dosing of amikacin in a Serratia marcescens endocarditis experimental model.

Once-daily dosage of aminoglycosides is currently under consideration. The lower toxicity of this regimen has been clearly established, but there are conflicting experimental and clinical data concerning its efficacy. It is inadvisable to optimize human therapy by extrapolation from experimental studies since animal and human pharmacokinetics differ. The simulation of human pharmacokinetics in experimental infectious models would seem to offer a more rational approach. We used computer-controlled infusion of amikacin at a variable flow rate to simulate human pharmacokinetics in a Serratia marcescens rabbit endocarditis model and to compare two therapeutic regimens (once-daily versus thrice-daily doses). The doses corresponded to simulations of 15 and 30 mg/kg of body weight per day in humans, and antibacterial activity was measured in vegetations (Veg) after 24 h of treatment. The results show that the dose corresponding to 15 mg/kg/day failed to produce a significant reduction of CFU (6.8 +/- 0.9 and 6.4 +/- 0.8 log10 CFU/g of Veg, respectively, for once-daily and thrice-daily doses versus 7.6 +/- 1.0 for controls). A significant reduction was observed only for the dose corresponding to 30 mg/kg/day in humans (5.2 +/- 1.5 and 5.4 +/- 1.1 log10 CFU/g of Veg, respectively, for the two regimens). With this model, the efficacy of amikacin was similar for both regimens after 24 h of treatment simulating human pharmacokinetics.

Amikacin↗
PubMed1995

Comparative efficacies of ciprofloxacin and pefloxacin alone or in combination with fosfomycin in experimental endocarditis induced by multidrug-susceptible and -resistant Pseudomonas aeruginosa.

The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133 rabbits by a multidrug-susceptible or multidrug-resistant strain of Pseudomonas aeruginosa. Therapy was initiated early (12 h after infection), when bacterial counts in aortic valve vegetations were relatively low, or late (48 h after infection), when vegetations contained a larger inoculum. Antibodies were administered as a continuous 24-h intravenous infusion. Mean steady-state levels of ciprofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/kg) in serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the multidrug-susceptible strain, all regimens except pefloxacin alone significantly reduced the number of CFU per gram of vegetation versus controls, whether treatment was performed early or late. For the multidrug-resistant strain, none of the regimens showed differences from untreated controls, except ciprofloxacin-fosfomycin, which significantly reduced bacterial counts in vegetations compared with controls when therapy was begun early (4.1 +/- 1.1 log10 CFU/g of vegetation; P < 0.001 versus the control). These data suggest that combination of fosfomycin with ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin alone for the therapy of severe infections caused by multidrug-susceptible P. aeruginosa.

Animals↗
PubMed1995

[Invasive aspergillosis in intensive care].

Invasive pulmonary aspergilloses occur in patients with antineoplasic chemotherapy, mainly when associated with a prolonged neutropenia, in transplanted patients with continuous corticotherapy and less frequently in immunocompetent surgical patients. The clinical features are those of an acute infective pneumonia, not responding to antibiotherapy. Radiologic signs are often non specific. Diagnosis is obtained with bronchoalveolar lavage in which Aspergillus is found both at direct examination and in culture. Serological tests are of little interest for the diagnosis of invasive aspergillosis. Extrapulmonary locations such as sinusitis, cutaneous or brain abscesses occur in 20% of cases. The gold standard of treatment is intravenous amphotericin B which elicits an acute reaction often followed by a nephrotoxic effect which can be decreased by fluid loading with saline. Oral itraconazole administration can follow the initial treatment with amphotericin B. The mortality rate remains high and an early diagnosis and an appropriate treatment are essential.

Amphotericin B↗
PubMed1994

Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminated Mycobacterium avium beige mouse model.

Capreomycin was incorporated into multilamellar vesicles of pure dipalmitoylphosphatidylcholine. The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice. The efficacies of the two forms were evaluated by using the Mycobacterium avium complex beige mouse model. Approximately 10(7) viable M. avium cells were injected intravenously. Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days. Mice were sacrificed 5 days after the end of treatment, and the viable bacteria in liver, spleen, lungs, and blood were counted. After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin. After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum. The 120-mg/kg dose of liposomal capreomycin significantly reduced the number of viable mycobacteria in the liver, spleen, and blood compared with those in the controls. Although these results are promising, further studies are needed to assess the efficacy of liposomal capreomycin for the treatment of M. avium complex infections.

Animals↗
PubMed1994

In vivo bactericidal activities of ciprofloxacin and pefloxacin in an experimental model of Serratia marcescens endocarditis.

The critical concentrations of pefloxacin and ciprofloxacin in serum, corresponding to the lowest concentration in serum able to achieve a 2-log-unit reduction in the CFU in vegetations after a 24-h exposure at a steady-state concentration obtained by a continuous intravenous infusion, were determined in an experimental model of Serratia marcescens endocarditis in rabbits. In vitro data showed that the MICs of ciprofloxacin and pefloxacin were 0.06 and 0.25 mg/liter, respectively. The killing curves indicated a maximum killing rate at a concentration four times that of the MICs. In vivo, the critical concentrations of pefloxacin and ciprofloxacin in serum were 0.4 and 0.24 mg/liter, respectively, corresponding to a concentration of four times the MICs.

Animals↗
PubMed1993

[Invasive aspergillosis in surgical intensive care patients].

Aspergillosis is a rare event in intensive care patients. Three cases of invasive aspergillosis due to Aspergillus fumigatus were diagnosed in a surgical critical care unit. Risk factors for aspergillosis were found in two liver transplanted patients. One of them had a primitive cutaneous aspergillosis, and the other, treatment difficulties due to the unavailability of an injectable preparation of itraconazole, a new triazole antifungal agent efficient against Aspergillus species. The third case occurred in a patient who had had surgery for gastric carcinoma with liver metastasis. The mycological examination of the air and workbench in the patients' rooms disclosed between 2 and 13 CFU.mm-3 of different Aspergillus species. Plasma itraconazole concentrations were measured in one patient only. They were below the therapeutic range, probably because of intestinal disturbances. The oral administration of itraconazole capsules through gastro-intestinal feeding tubes results in a poor availability of the drug. Such a technique of administration should therefore be undertaken with larger doses than those commonly recommended. Moreover, itraconazole plasma concentrations should be monitored. The association with amphotericin B is recommended until normal intestinal absorption has been obtained.

Adult↗
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↗