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Gilles Potel

Publications and source records attributed to Gilles Potel.

At least 19 recordsLinked to original sources
PubMed2006

Trough serum concentrations of beta-lactam antibiotics in cancer patients: inappropriateness of conventional schedules to pharmacokinetic/pharmacodynamic properties of beta-lactams.

Serum concentrations of beta-lactams that continuously exceed the minimum inhibitory concentration may improve therapeutic outcomes for immunosuppressed patients. The trough serum levels of ceftazidime (CAZ), cefepime (FEP) or imipenem (IMP) were prospectively determined on days 1 and 3 of treatment in cancer patients. Seventy-eight episodes of suspected infection were analysed. Trough serum levels were higher than 4 mg/L in 62%, 24% and 0% of cases in the CAZ, FEP and IMP groups, respectively, and were higher than 20 mg/L in 24% of cases in the CAZ group compared with 0% both in the FEP and IMP groups. For suspected infectious episodes in cancer patients, the traditional intermittent regimen of beta-lactams does not appear to be appropriate for the pharmacokinetic/pharmacodynamic properties of these antibiotics.

Adult↗
PubMed2006

[Heat stroke in hospital patients during the summer 2003 heat wave: a nosocomial disease].

OBJECTIVE: We investigated patients who died in our institution during the August 2003 heat wave, to determine whether some in hospital patients actually died of heat stroke. METHODS: Records of all patients who died in our tertiary care hospital between 6-15 August 2003 were analyzed retrospectively. Heat stroke was considered the cause of death when the following criteria were met: body temperature higher than 40.5 degrees C, except if there was documented evidence of cooling before the first temperature measurement, central nervous system abnormalities, and a reliable history of exposure to high temperatures in a hospital ward. The number of patients who died in the hospital during the heat wave was compared with data from the previous year. RESULTS: Seventeen patients died from hospital-acquired heat stroke (19% of all hospital deaths). This condition accounted for a 25% increase in hospital mortality over the same period during 2002. COMMENT: Hospital-acquired heat stroke appears to be a nosocomial disease that was responsible for an overall increase in hospital mortality during the 2003 heat wave.

Aged↗
PubMed2006

Effectiveness of linezolid and imipenem association in the treatment of severe community-acquired pneumonia in children: two case reports.

Two children with severe pneumonia, purulent pleural effusions, and abscess formation unresponsive to appropriate antibiotic therapy recovered promptly after the introduction of linezolid and imipenem association. Linezolid is a new antibiotic with high bioavailability and an outstanding safety profile, synergistic with imipenem, which may deserve a place in the armamentarium for severe pneumonia in children.

Acetamides↗
PubMed2006

In vitro and in vivo assessment of linezolid combined with ertapenem: a highly synergistic combination against methicillin-resistant Staphylococcus aureus.

Linezolid in combination with ertapenem showed in vitro synergy against methicillin-resistant Staphylococcus aureus strains. We confirmed this interaction in vivo by using a rabbit endocarditis experimental model and simulation of the human pharmacokinetics in animals for both antibiotics. Linezolid plus ertapenem exhibited highly synergistic activity in vivo after 4 days of treatment.

Acetamides↗
PubMed2005

Eagle effect in Corynebacterium diphtheriae.

The in vivo relevance of the paradoxical bactericidal effect (the Eagle effect) is not evident. We found in vitro a paradoxical bactericidal effect of amoxicillin on 2 strains of nontoxigenic Corynebacterium diphtheriae. Then, using an experimental rabbit model of endocarditis, we evaluated the in vivo relevance of this phenomenon. Rabbits were assigned to the following groups: no treatment (control group), continuous amoxicillin infusion simulating a dosage of 200 mg/kg/day in humans, and continuous amoxicillin infusion simulating a dosage of 20 mg/kg/day in humans. The low dosage (20 mg/kg/day) was significantly more effective than the high dosage (200 mg/kg/day) against both strains (P<.025), confirming the paradoxical bactericidal effect observed in vitro.

Amoxicillin↗
PubMed2005

The effects of milrinone on hemodynamics in an experimental septic shock model.

OBJECTIVE: To investigate the specific hemodynamic effects of the phosphodiesterase inhibitor milrinone in a rabbit model of septic shock in the absence of any other treatment. DESIGN: A prospective, controlled, interventional study. Animal Model: Fourteen sedated New Zealand rabbits. SETTING: Research laboratory of a health sciences university. INTERVENTIONS: Rabbits were anesthetized and vascular catheters inserted in femoral artery and jugular vein. After a stabilization period and the recording of baseline measurements (H0), all animals received a 10-mL infusion of Pseudomonas aeruginosa. Two hours later (H2rabbits were randomly assigned to receive 5% dextrose (control group) or milrinone (milrinone group). MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP) was monitored continuously, and a cardiac index (CI) was determined every 30 mins by a transpulmonary thermodilution technique using an integrated monitoring device (PICCO). No differences were detected between the two groups after stabilization (H0) or before the treatment (H2) for either CI (mL/min(-1)/kg(-1)) or MAP (mm Hg). CI decreased progressively in the control group during the following 4 hrs, but not in the treated group (at H6: 122 +/- 4 vs. 207 +/- 16 mL/min(-1)/kg(-1); p < .05). No drop of MAP occurred after milrinone infusion. A comparison of the treated and control group reveals that milrinone improved tissue perfusion as evidenced by measurements of central venous saturation (at H4: 0.59 +/- 0.05 vs. 0.71 +/- 0.03, p = .04), lactacidemia (at H6: 10.3 +/- 2.4 vs. 3.9 +/- 0.9 mmol/L, p = .03), creatinemia (at H6: 95 +/- 11 vs. 60 +/- 5 micromol/L, p = .02) and survival (at H6: 5 vs. 7, not significant). CONCLUSION: Milrinone improves cardiac output and tissue perfusion in a rabbit model involving severe septic shock.

Animals↗
PubMed2005

In vitro and in vivo synergistic activities of linezolid combined with subinhibitory concentrations of imipenem against methicillin-resistant Staphylococcus aureus.

Indifference or moderate antagonism of linezolid combined with other antibiotics in vitro and in vivo have mainly been reported in the literature. We have assessed the in vitro activities of linezolid, alone or in combination with imipenem, against methicillin-resistant Staphylococcus aureus (MRSA) strains using the dynamic checkerboard and time-kill curve methods. Linezolid and low concentrations of imipenem had a synergistic effect, leading us to evaluate the in vivo antibacterial activity of the combination using the rabbit endocarditis experimental model. Two MRSA strains were used for in vivo experiments: one was a heterogeneous glycopeptide-intermediate clinical S. aureus strain isolated from blood cultures, and the other was the S. aureus COL reference strain. Animals infected with one of two MRSA strains were randomly assigned to one of the following treatments: no treatment (controls), linezolid (simulating a dose in humans of 10 mg/kg of body weight every 12 h), a constant intravenous infusion of imipenem (which allowed the steady-state concentration of about 1/32 the MIC of imipenem for each strain to be reached in serum), or the combination of both treatments. Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.

Acetamides↗
PubMed2005

Activity of glycopeptides against Staphylococcus aureus infection in a rabbit endocarditis model: MICs do not predict in vivo efficacy.

The in vivo efficacy of vancomycin and teicoplanin against five Staphylococcus aureus strains with different susceptibilities to them and methicillin was studied. Rabbits were allocated at random to groups for endocarditis induction with one of these five strains and then treated for 2 days with vancomycin or teicoplanin. Each treated group was compared with a control group infected with the same strain. Vancomycin and teicoplanin showed similar activities. Low MICs did not predict better in vivo results.

Animals↗
PubMed2004

Comparison of in vivo intrinsic activity of cefepime and imipenem in a Pseudomonas aeruginosa rabbit endocarditis model: effect of combination with tobramycin simulating human serum pharmacokinetics.

OBJECTIVES: The purpose of this experimental study was first to compare the in vivo intrinsic activity of imipenem and cefepime administered as a continuous infusion and to determine their lowest effective serum steady-state concentration (LESSC). Secondly, we studied the effect of combining therapy with tobramycin. METHODS: In a Pseudomonas aeruginosa (ATCC 27853) rabbit endocarditis model, beta-lactam antibiotics were administered by continuous infusion over a 24 h treatment period at different doses until the LESSC was reached, i.e. able to achieve a 2-log drop of cfu/g of vegetations versus untreated animals. The effect of adding tobramycin (3 mg/kg once daily) was then studied. RESULTS: The LESSC was between 3 x and 4 x MIC of cefepime for P. aeruginosa and about 0.2 5x MIC of imipenem. Combination of tobramycin with each of the two beta-lactams did not result in any further significant killing. CONCLUSION: The optimal Css/MIC ratio might differ from one molecule to another. The LESSC of imipenem is lower than that of cefepime, giving a better intrinsic activity in vivo, despite a higher MIC in vitro.

Animals↗
PubMed2004

[Non-justified visits to emergency units. Proposal of differentiated care].

OBJECTIVE: The number of visits to emergency units in public hospital settings in France increases every year. The adequation between admission to an SAU--Service d'accueil d'urgence (emergency unit) and the clinical status of the patient must be checked to improve handling upstream of the SAU. METHOD: A prospective study was conducted in the SAU of the University Hospital in Nantes to assess the proportion of patients who would benefit from direct hospitalisation, scheduled in a department of specialised or polyvalent medicine. RESULTS: This proportion was of 10%. Seventy-three percent of the patients were aged over 60. They were referred in 77% of cases by their treating physician and in 10.4% of cases by the physician on duty. Thirty-three percent of cases were non-specified organ diseases, 20% were dermatological affections, 12% broncho-pulmonary infections and in the same proportion rheumatological pathologies; other affections were rare. COMMENTS: The results of this study must be confirmed in a pilot study in which the general practitioner would refer any patient, that he would have sent to an SAU, directly to a medical department without passing through the SAU. To do so, using a cell phone, the practitioner would contact the hospital physician who would find a hospital bed. The impact of this new modality of hospitalisation on the SAU could be assessed in terms of the number of admissions avoided to the SAU.

Aged↗
PubMed2004

[Meningitis with direct negative bacteriological examination. Prospective assessment of a decision making tree].

OBJECTIVE: Elaboration of a decision-making tree for differential diagnosis of bacterial and viral meningitis, when initial Gram's staining is negative. Method One-Year prospective study in an adult emergency department. Comparison with the immediately-preceding period. RESULTS: 56 patients were included. Only 4 bacterial meningitis, but none misdiagnosed. 86% sensitivity and 83% specificity for viral meningitis (n=40). Rate of patients hospitalised more than 24 hours decreasing from 62.5 to 41% (p=0.05). Antibiotic chemotherapy decreasing from 55 to 16% (p<0.001). CONCLUSION: This decision-making tree safely allows emergency differentiation between bacterial and viral meningitis, when initial Gram's staining is negative. It consequently leads to decreased rates of useless hospitalisations and antibiotic treatments. We believe that this method can be helpful during outbreaks of viral meningitis.

Adult↗
PubMed2004

In vivo efficacy of linezolid in combination with gentamicin for the treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Indifference or even antagonism has mainly been reported with combinations including linezolid. The presence of in vitro antagonism is not always correlated with in vivo failure. The purpose of this study was to evaluate the in vivo activity of linezolid combined with gentamicin using a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis experimental model. A human-like pharmacokinetic simulation was used for linezolid and gentamicin to improve the extrapolation of the results to human therapy. Contrary to the antagonism previously described in vitro, linezolid combined with gentamicin exhibited bactericidal activity on the two strains with a decrease of at least 4 log(10)cfu/g of vegetation compared with controls. These data suggest that linezolid plus gentamicin could be an appropriate combination for the treatment of severe MRSA infections.

Acetamides↗
PubMed2003

[Antibiotic therapy: from pharmacology to decision making].

The decision of an antibiotic treatment depends first on clinical and bacteriological data. Then PK/PD (pharmacodynamics/pharmacokinetics) of antibiotics must be taken into account in order to optimise the dosing regimen, and to reach the targeted serum concentrations. The good oral bioavailability of some drugs allows the use of the oral route, at the beginning of the treatment, or shortly after an initial successful i.v. administration, even in severe infections.

Anti-Bacterial Agents↗
PubMed2003

In vitro activity of linezolid alone and in combination with gentamicin, vancomycin or rifampicin against methicillin-resistant Staphylococcus aureus by time-kill curve methods.

The in vitro activity of the oxazolidinone linezolid was studied alone and in combination with three antibiotics acting on different cellular targets. Oxazolidinones are bacterial protein synthesis inhibitors that act at a very early stage by preventing the formation of the initiation complex. Combinations of linezolid with gentamicin, vancomycin or rifampicin were evaluated against four methicillin-resistant Staphylococcus aureus strains, using killing curves in conjunction with scanning electron microscopy. Time-kill curves were performed over 24 h using an inoculum of 5 x 10(6)- 1 x 10(7) cfu/mL. Linezolid was studied at concentrations of 1 x, 4 x and 8 x MIC, with partner drugs at 8 x MIC. Addition of linezolid resulted in a decrease of antibacterial activity for gentamicin and vancomycin, and linezolid was antagonistic to the early bactericidal activity of gentamicin. Linezolid, in combination with rifampicin, showed an additive interaction for susceptible strains and inhibited rifampicin-resistant variants. Linezolid plus rifampicin appeared to be the most active combination against methicillin-resistant S. aureus strains in time-kill experiments.

Acetamides↗
PubMed2003

Simulation of human gentamicin pharmacokinetics in an experimental Enterococcus faecalis endocarditis model.

Significant differences between animal and human pharmacokinetics may be responsible for the conflicting results of experimental studies. This study determined the impact of human pharmacokinetic simulation (HPS) on gentamicin activity in an Enterococcus faecalis endocarditis model. The decrease in bacterial counts was greater with HPS than with a dose-equivalent regimen without HPS.

Animals↗
PubMed2002

In vivo efficacy of continuous infusion versus intermittent dosing of linezolid compared to vancomycin in a methicillin-resistant Staphylococcus aureus rabbit endocarditis model.

Linezolid is the first drug issued from the oxazolidinones, a novel class of antimicrobial agents with potent activity against gram-positive pathogens. A rabbit endocarditis model was used to compare the in vivo activities of different linezolid regimens mimicking intermittent dosing of 10 mg/kg of body weight every 12 h for 5 days or continuous (constant-rate) infusion of a daily dose of 20 mg/kg (for 5 days) or 40 mg/kg (for 3 and 5 days) and the activities of intermittent dosing and continuous infusion of vancomycin (for 5 days). The in vivo activities of these regimens were tested against three strains of methicillin-resistant Staphylococcus aureus. A human-like pharmacokinetic simulation was used for linezolid in order to improve the extrapolation of the results to human therapy. All linezolid regimens significantly reduced the numbers of S. aureus cells in aortic valve vegetations compared to the numbers in the control groups. Linezolid intermittent dosing had an in vivo bacteriostatic effect. Switching from intermittent dosing to continuous infusion (at the same dose) led to in vivo bactericidal activity, with a decrease of at least 3 log(10) CFU/g of vegetation compared to the counts for the controls. After 5 days of treatment, continuous infusion of linezolid (corresponding to a daily dose of 40 mg/kg in humans) seemed to be at least as effective as vancomycin against the three strains. No resistant variant was isolated from the vegetations during any of the treatments. These data suggest that continuous infusion of linezolid could be an appropriate alternative to the use of glycopeptides for the treatment of severe methicillin-resistant S. aureus infections.

Acetamides↗