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Pascual A.,Institute Of Recherche Biomedicale Des Armees | Pascual A.,Aix - Marseille University | Pascual A.,Center National Of Reference Du Paludisme | Madamet M.,Aix - Marseille University | And 20 more authors.
Malaria Journal | Year: 2015

Background: In 2002, the World Health Organization recommended that artemisinin-based combination therapy (ACT) be used to treat uncomplicated malaria. Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new combinations. The aim of the present work was to assess the distribution of the in vitro values of pyronaridine (PND) and piperaquine (PPQ) and to define a cut-off for reduced susceptibility for the two anti-malarial drugs. Methods: The distribution and range of the 50% inhibitory concentration values (IC50) of PND and PPQ were determined for 313 isolates obtained between 2008 and 2012 from patients hospitalized in France for imported malaria. The statistical Bayesian analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to PND and PPQ. Results: The PND IC50 values ranged from 0.6 to 84.6 nM, with a geometric mean of 21.1 ± 16.0 nM (standard deviation). These values were classified into three components. The PPQ IC50 values ranged from 9.8 to 217.3 nM, and the geometric mean was 58.0 ± 34.5 nM. All 313 PPQ values were classified into four components. Isolates with IC50 values greater than 60 nM or four-fold greater than 3D7 IC50 are considered isolates that have reduced susceptibility to PND and those with IC50 values greater than 135 nM or 2.3-fold greater than 3D7 IC50 are considered isolates that have reduced susceptibility to PPQ. Conclusion: The existence of at least three phenotypes for PND and four phenotypes for PPQ was demonstrated. Based on the cut-off values, 18 isolates (5.8%) and 13 isolates (4.2%) demonstrated reduced susceptibility to PND and PPQ, respectively. © 2015 Pascual et al.; licensee BioMed Central. Source

Gaillard T.,Institute Of Recherche Biomedicale Des Armees | Gaillard T.,Aix - Marseille University | Gaillard T.,Federation des Laboratoires | Sriprawat K.,Mahidol University | And 17 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

Determinations of doxycycline 50% inhibitory concentrations (IC50) for 620 isolates from northwest Thailand were performed via the isotopic method, and the data were analyzed by the Bayesian method and distributed into two populations (mean IC50s of 13.15 μM and 31.60 μM). There was no significant difference between the group with low IC50s versus the group with high IC50s with regard to copy numbers of the Plasmodium falciparum tetQ (pftetQ) gene (P = 0.11) or pfmdt gene (P = 0.87) or the number of PfTetQ KYNNNN repeats (P = 0.72). Copyright © 2015, American Society for Microbiology. All Rights Reserved. Source

Pascual A.,Institute Of Recherche Biomedicale Des Armees | Pascual A.,Center National Of Reference Du Paludisme | Parola P.,Institut Universitaire de France | Benoit-Vical F.,Toulouse University Hospital Center | And 14 more authors.
Malaria Journal | Year: 2012

Background: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN). Methods. The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours 3H-hypoxanthine uptake inhibition method. Results: The IC 50values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC 50and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs. Conclusions: In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs. © 2012 Pascual et al; licensee BioMed Central Ltd. Source

Commandeur D.,Federation danesthesie reanimation urgences | Giacardi C.,Federation danesthesie reanimation urgences | Danguy Des Deserts M.,Federation danesthesie reanimation urgences | Huynh S.,Federation danesthesie reanimation urgences | And 3 more authors.
Medecine et Maladies Infectieuses | Year: 2011

Objectives: The study objectives were to check whether recommended vancomycin doses were related to pharmacological objectives for intensive care patients: steady-state plasma concentration (SSc) and ratio SSc/MIC (Minimal Inhibiting Concentration). The authors tried to identify variability factors for vancomycin plasmatic concentrations at peak. Patients and methods: This monocentric, observational, and retrospective survey was performed on 66 intensive care patients treated by antibiotics including vancomycin, alone or in combination, as a curative treatment for a severe infection with Gram-positive bacteria. Vancomycin was dosed at 15. mg/kg during the first hour, then 40 to 60. mg/kg per 24. hour. Vancomycin SSc and bacteria MIC were recorded. The SSc/MIC ratio was determined and was considered efficient when superior to 8. Results: Forty-two percent of vancomycin SSc were within the effectiveness rate. Twenty-three percent of SSc/MIC ratios were superior to 8. The rate of clinical recovery was 71 %. The length of antibiotherapy was identified as positively interacting with biological effectiveness, unlike severe sepsis, a factor of negative interaction on vancomycin SSc in this study. Conclusion: Less than half of the SSc and less than a quarter of the SSc/MIC ratios were at effective rates in our study. Therefore, adequacy between dosage, administration, and monitoring should be reviewed. © 2011 Elsevier Masson SAS. Source

Mokhtari C.,Center National Of Reference Des Hepatites E | Marchadier E.,Center National Of Reference Des Hepatites E | Haim-Boukobza S.,Center National Of Reference Des Hepatites E | Haim-Boukobza S.,University Paris - Sud | And 7 more authors.
Journal of Clinical Virology | Year: 2013

Background: Hepatitis E virus (HEV) is an increasing cause of acute viral hepatitis in developed countries. Serological testing alone may fail to diagnose acute infection, especially in immunocompromised patients, which justifies the use of molecular assays for diagnosis. Few studies have compared accuracy of HEV RNA detection assays. Objectives: The performances of five real-time PCR procedures for HEV RNA detection were compared. Study design: First, RNA quantification of hepatitis E diluted standards of 3a and 3b genotypes were performed. Secondly, forty-seven clinical samples of patients with known acute HEV infection were tested using five hepatitis E RNA detection methods of assigned letters A, B, C, D and E. Results: Standards of HEV 3a genotype were detected in 100% of replicates with 2500. UI/ml of sensitivity by using A, B and C assays. Standards of HEV 3b genotype were more accurately detected with a sensitivity of 25. UI/ml in 100% of replicates using C assay and were detected in 100% of replicates with 2500. UI/ml of sensitivity by using A, B and E assays. Overall, B assay detected all of 250. UI/ml dilution and occasionally the 25. UI/ml dilution on both subtypes. The detection rates of clinical samples were 100%, 100% 97%, 97% and 83% for the respective A, B, C, D and E assay. Assays A and B were well correlated, independently of the subtype. However, discrepancies were observed when these techniques were compared to C, D and E assays according to the different subtypes. Conclusion: A and B assays appear reliable for HEV RNA detection. These assays target the ORF2/3 overlapping region, described as more conserved than ORF2. © 2013 Elsevier B.V. Source

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