Laurence Armand-Lefevre

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (35)145.59 Total impact

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    ABSTRACT: Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia (VAP) and evaluate several dosage regimens.
    British Journal of Clinical Pharmacology 06/2014; · 3.58 Impact Factor
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    ABSTRACT: We describe the prevalence of carriage and variables associated with introduction of highly drug-resistant microorganisms (HDRMO) into a French hospital via patients repatriated or recently hospitalized in a foreign country. The prevalence of HDRMO was 11% (15/132), with nine carbapenamase-producing Enterobacteria-ceae, nine carbapenem-resistant Acinetobacter baumannii and six glycopeptide-resistant enterococci. Half of the admitted patients (63/132, 48%) were colonized with extended spectrum beta-lac-tamase-producing Enterobacteriaceae (ESBLPE). Among the four episodes with secondary cases, three involved A. baumannii.
    Clinical Microbiology and Infection 04/2014; · 4.58 Impact Factor
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    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2014; 19(14). · 5.49 Impact Factor
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    ABSTRACT: We retrospectively studied daptomycin use during 2010 at the Bichat-Claude-Bernard teaching-hospital (Paris) to observe the evolution of daptomycin prescriptions. Twenty-one patients were included and several parameters were documented: site of infection, bacterial species involved, reason for daptomycin use, dose and clinical outcome. Ninety-five percent of daptomycin prescritions were off-label and most did not comply with local guidelines. Fifteen of the 21 patients were cured (71%), including 9 patients of the 12 with off-label and off-local recommendation prescriptions (75%). Osteitis and Enterococcus spp endocarditis were the new indications. Daptomycin was increasingly used at higher doses: 52% of our patients were given doses above 6mg/kg. Staphylococcus spp. was the most frequent pathogen responsible for infection is our patients, followed by Enterococcus spp. Daptomycin use is likely to evolve because of its effectiveness in the treatment of osteitis, left-sided and Enterococcus spp. infective endocarditis. It is generally used at higher doses, which are well tolerated. However, therapeutic monitoring needs to be developed. The antibiotic commission of our hospital gave new recommendations for daptomycin use in 2011.
    Médecine et Maladies Infectieuses 12/2013; · 0.75 Impact Factor
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    ABSTRACT: The increasing prevalence of extended spectrum beta-lactamase producing enterobacteriaceae (ESBLPE) requires defining the use of carbapenems in first intention. We analyzed the associations between enterobacteriaceae bacteremia (EbBact) and ESBLPE carriage during 10 years in a 950-bed teaching hospital. We analyzed a 10-year (July 2001 to June 2011) prospective collection of bacteremia cases including 2 databases: (1) EbBact and (2) a computerized database of patients carrying EBLSE. Only one episode of EbBact was analyzed per patient and hospital stay. Factors associated with ESBLPE bacteremia were assessed by univariate and multivariate logistic regression analysis. Overall, 2355 cases of EbBact were identified, among which 135 (5.7%) were ESBLPE (2001-05: 1.4%, 2006-09: 7.6%, 2010-11: 14.2%). ESBLPE bacteremia was observed in 52 of the 88 (59%) patients carrying ESBLPE and in 83/2267 (3.7%) patients not known to be colonized with ESBLPE. Factors associated with ESBLPE bacteremia in patients not known to be colonized were: female gender (ORa=0.56, CI95% [0.34-0.91]), hospitalization in the ICU (ORa=2.51 [1.27-5.05]) or medical/surgical wards (ORa=1.83 [1.04-3.38]), the period (2006-09, ORa=4.08 [2.21-8.16]; 2010-11, ORa=8.17 [4.14-17.06] compared to 2001-05), and history of EbBact (ORa=2.29 [0.97-4.79]). In case of EbBact, patients known to be colonized with ESBLPE present with ESBLPE bacteremia in more than half of the cases, requiring carbapenems as empirical antibiotic treatment. The global prevalence of ESBLPE among patients presenting with EbBact not known to be colonized with ESBLPE was 3.7%.
    Médecine et Maladies Infectieuses 12/2013; · 0.75 Impact Factor
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    ABSTRACT: According to French national recommendations, the detection of a patient colonized with glycopeptide-resistant enterococci (GRE) leads to interruption of new admissions and transfer of contact patients (CPs) to another unit or healthcare facility, with weekly screening of CPs. We evaluated the medical and economic impact of a pragmatic adaptation of national guidelines associated with a real-time PCR (RTP) (Cepheid XpertTM vanA/vanB) as part of the strategy for controlling GRE spread in two medical wards. Screening was previously performed using chromogenic selective medium (CSM). Turn around time (TAT), costs of tests and cost of missed patient days were prospectively collected. In February 2012, the identification of GRE in one patient in the diabetology ward led to the screening of 31 CPs using CSM; one secondary case was identified in a CP already transferred to the Nephrology ward. Awaiting the results of SCM (median TAT, 70.5 h), 41 potential patient days were missed, due to interruption of admissions. The overall cost (screening tests + missing patient.days) was estimated at 14, 302.20 [euro sign]. The secondary case led to screening of 22 CPs in the Nephrology ward using RTP. Because of a short median TAT of 4.6 h, we did not interrupt admissions and patients' transfers. Among 22 CPs, 19 (86%) were negative for vanA, 2 were positive for vanB and 3 had invalid results needing CSM. The overall cost of the strategy was estimated at 870.40 [euro sign] (cost of screening tests only), without missing patient days. The rapid PCR test for vanA-positive GRE detection both allowed rapid decision about the best infection control strategy and prevented loss of income due to discontinuation of patient transfers and admissions.
    Antimicrobial resistance and infection control. 11/2013; 2(1):30.
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    ABSTRACT: Extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBL E. coli) strains are of major concern because few antibiotics remain active against these bacteria. We investigated the association between the fecal relative abundance (RA) of ESBL-producing E. coli (ESBL-RA) and the occurrence of ESBL E. coli urinary tract infections (UTIs). The first stool samples passed after suspicion of UTI from 310 women with subsequently confirmed E. coli UTIs were sampled and tested for ESBL-RA by culture on selective agar. Predictive values of ESBL-RA for ESBL E. coli UTI were analyzed for women who were not exposed to antibiotics when the stool was passed. ESBL E. coli isolates were characterized for ESBL type, phylogroup, relatedness, and virulence factors. The prevalence of ESBL E. coli fecal carriage was 20.3%, with ESBL E. coli UTIs being present in 12.3% of the women. The mean ESBL-RA (95% confidence interval [CI]) was 13-fold higher in women exposed to antibiotics at the time of sampling than in those not exposed (14.3% [range, 5.6% to 36.9%] versus 1.1% [range, 0.32% to 3.6%], respectively; P < 0.001) and 18-fold higher in women with ESBL E. coli UTI than in those with another E. coli UTI (10.0% [range, 0.54% to 100%] versus 0.56% [range, 0.15% to 2.1%[, respectively; P < 0.05). An ESBL-RA of <0.1% was 100% predictive of a non-ESBL E. coli UTI. ESBL type, phylogroup, relatedness, and virulence factors were not found to be associated with ESBL-RA. In conclusion, ESBL-RA was linked to the occurrence of ESBL E. coli UTI in women who were not exposed to antibiotics and who had the same clone of E. coli in urine samples and fecal samples. Especially, a low ESBL-RA appeared to be associated with a low risk of ESBL E. coli infection.
    Antimicrobial Agents and Chemotherapy 09/2013; 57(9). · 4.57 Impact Factor
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    Antimicrobial Resistance and Infection Control. 06/2013; 2(1).
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    ABSTRACT: Background The duration of gastrointestinal colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) may play a major role in the spread of these organisms. We evaluated the time to, and factors associated with, ESBL-E clearance after hospital discharge. Methods We retrospectively reviewed prospective surveillance results obtained over 14 years in a 1,000-bed hospital. The surveillance collected demographic, hospital stay, microbiologic, and outcome data. An automatic alert system identified readmitted patients with prior ESBL-E carriage. ESBL-E clearance was defined as a negative rectal screening sample at readmission with no new positive clinical sample during the stay. Variables associated with ESBL-E clearance were identified using a Cox model. Results We included 1,884 patients with 2,734 admissions. Four hundred forty-eight patients with readmission screening formed the basis for the study. Of 448 patients with 1 to 16 readmissions, 180 (40%) were persistent carriers. The median time to ESBL-E clearance was 6.6 months. Variables independently associated with clearance was having the first positive culture in a screening sample only (adjusted hazard ratio, 1.31; 95% confidence interval, 1.02-1.69; P = .04) and period 2005-2010 (hazard ratio, 1.88; 95% confidence interval, 1.33-2.67; P < .01). Conclusion We found a long duration of ESBL-E carriage after hospital discharge. An automatic alert system was useful for identifying, screening, and isolating previous ESBL-E carriers.
    American journal of infection control 05/2013; 41(5):443–447. · 3.01 Impact Factor
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    ABSTRACT: Time-to-positivity (TTP) of first positive blood cultures growing Gram-negative bacilli (GNB) was investigated. When anaerobic vials were positive first, TTP≤18hours differentiated Enterobacteriaceae from strict anaerobic Gram-negative bacilli (PPV 98.8%). When the aerobic ones were first, TTP≤13hours differentiated Enterobacteriaceae from Pseudomonas aeruginosa and other GNB (PPV 80.8%).
    Journal of microbiological methods 02/2013; · 2.43 Impact Factor
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    ABSTRACT: Intestinal flora contains a reservoir of gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case-control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36 P. aeruginosa, 12 S. maltophilia, 6 Enterobacteriaceae, and 2 A. baumannii. In P. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In the Enterobacteriaceae strains, resistance was due to AmpC cephalosporinase and/or extended-spectrum β-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 producing P. aeruginosa, 2 K. pneumoniae and 2 S. maltophilia). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% CI, 1.5-25.7) after 1-3 days of exposure and increased to 7.8 (95% CI, 2.4-29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.
    Antimicrobial Agents and Chemotherapy 01/2013; · 4.57 Impact Factor
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  • European Urology Supplements 02/2012; 11(1):e38, e38a. · 2.16 Impact Factor
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    ABSTRACT: Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae have become prevalent in both the hospital and the community. We describe the epidemiology of ESBL-producing isolates and patient characteristics at hospital admission. Data on clinical properties, medical history, previous hospitalizations, and previous antibiotic treatments were collected. ESBL genes (bla(CTX-M), bla(TEM), and bla(SHV)) were identified by polymerase chain reaction. One hundred and sixteen patients carried 122 ESBL-producing Enterobacteriaceae: 79 Escherichia coli, 26 Klebsiella pneumoniae, 16 Enterobacter spp., and 1 Citrobacter koseri. ESBL-producing E. coli were associated with admission from home (odds ratio (OR) 3.04, p = 0.02) and a history of recent urinary tract infection (OR 3.38, p = 0.04), and exhibited a lower rate of antimicrobial resistance to aminoglycosides (p ≤ 0.005) and co-trimoxazole (p = 0.003), whereas other ESBL-producing Enterobacteriaceae tended to be associated with a recent surgery (OR 0.42, p = 0.057). Although the CTX-M enzymes were more frequently found in E. coli (76%), they were also identified in other Enterobacteriaceae (45%), suggesting penetration of CTX-M-type enzymes into both community- and hospital-acquired enterobacterial species.
    Scandinavian Journal of Infectious Diseases 11/2011; 44(3):231-6. · 1.71 Impact Factor
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    ABSTRACT: From the time of CTX-M emergence, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have spread worldwide in community settings as well as in hospitals, particularly in developing countries. Although their dissemination appears linked to Escherichia coli intestinal carriage, precise paths of this dynamic are largely unknown. Children from a pediatric renutrition center were prospectively enrolled in a fecal carriage study. Antibiotic exposure was recorded. ESBL-E strains were isolated using selective media from fecal samples obtained at admission and, when negative, also at discharge. ESBL-encoding genes were identified, their environments and plasmids were characterized, and clonality was assessed with polymerase chain reaction-based methods and pulsed-field gel electrophoresis for E. coli and Klebsiella pneumoniae. E. coli strains were subjected to multilocus sequence typing. The ESBL-E carriage rate was 31% at admission in the 55 children enrolled. All children enrolled received antibiotics during hospitalization. Among the ESBL-E-negative children, 16 were resampled at discharge, and the acquisition rate was 94%. The bla(CTX-M-15) gene was found in >90% of the carriers. Genetic environments and plasmid characterization evidenced the roles of a worldwide, previously described, multidrug-resistant region and of IncF plasmids in CTX-M-15 E. coli dissemination. Diversity of CTX-M-15-carrying genetic structures and clonality of acquired ESBL E. coli suggested horizontal genetic transfer and underlined the potential of some ST types for nosocomial cross-transmission. Cross-transmission and high selective pressure lead to very high acquisition of ESBL-E carriage, contributing to dissemination in the community. Strict hygiene measures as well as careful balancing of benefit-risk ratio of current antibiotic policies need to be reevaluated.
    Clinical Infectious Diseases 10/2011; 53(7):677-85. · 9.37 Impact Factor
  • N. Grall, A. Andremont, L. Armand-Lefèvre
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    ABSTRACT: Carbapenem resistance in Gram-negative bacilli poses a serious threat as it leads to therapeutic dead-end. It might be achieved through selective loss of external membrane permeability (such as OprD porin loss in Pseudomonas aeruginosa), combination of impermeability with various wide-spectrum β-lactamases (extended-spectrum β-lactamase [ESBL] and/or cephalosporinase) or carbapenem-hydrolyzing enzymes i.e., carbapenemases. The latter are of concern as their respective encoding genes are carried by transmissible genetic elements that leads to a wide and rapid dissemination. Carbapenemases encompass heterogeneous enzymes of which denominator is to hydrolyze at least one carbapenem. The most prevalent are KPC (Ambler class A), VIM, IMP, NDM (class B), OXA-48 and OXA-23 (class D). They have been described in a large subset of bacterial species (Enterobacteriaceae, P. aeruginosa and Acinetobacter baumannii). Carbapenemases have been isolated worldwide, yet some countries appear to be specifically stricken. In France, isolation of carbapenem-producing bacteria is still uncommon and most cases are imported. In order to prevent in-hospital dissemination of such superbugs, recently published recommendations from the French High Committee of Public Health have to be applied.
    Journal des Anti-infectieux. 06/2011; 13(2).
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    ABSTRACT: We report incidental isolation of an OXA-48-producing Escherichia coli strain in urine of a 62-year-old woman recently returning from a 2-month vacation in Morocco. Commercially available extended-spectrum beta-lactamase (ESBL)-targeting medium failed to detect it in the patient's stools, although a locally developed and easy-to-implement method using ertapenem-supplemented brain heart infusion (BHI) broths could.
    Journal of clinical microbiology 05/2011; 49(7):2761-2. · 4.16 Impact Factor
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    ABSTRACT: The impact of high level cephalosporin resistance due to Enterobacteriaceae harbouring a type I-inducible chromosomal β-lactamase on the outcome of ventilator-associated pneumonia (VAP) remains unknown. A retrospective cohort study was conducted in two intensive care units (ICUs) over a four-year period to identify factors prognostic of VAP caused by high level AmpC (HL-AmpC)-producing Enterobacteriaceae. The study included 75 patients, who developed VAP due to Enterobacteriaceae harbouring a type I-inducible chromosomal β-lactamase. One-third of these VAP episodes were due to HL-AmpC-producing Enterobacteriaceae. Demographic and clinical characteristics at ICU admission were similar for patients, regardless of Enterobacteriaceae susceptibility, but those who developed VAP due to HL-AmpC-producing Enterobacteriaceae received antibiotics more frequently before its onset and had higher disease severity and organ dysfunction scores. Enterobacter spp. were the major HL-AmpC-producing micro-organisms responsible for VAP. VAP due to HL-AmpC-producing Enterobacteriaceae is rare. High level cephalosporin resistance was not associated with higher day 28 mortality, despite its association with more severe disease at VAP onset.
    The Journal of hospital infection 01/2011; 77(1):64-9. · 3.01 Impact Factor
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    ABSTRACT: The aims of the study were to determine the in vitro activity of doripenem, a new carbapenem, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorization in France according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. The MICs of doripenem were determined by the broth microdilution method against 1,547 clinical isolates from eight French hospitals. The disk diffusion test was performed (10-μg discs) according to the Comité de l'Antibiogramme de la Société Française de Microbiologie (CASFM) method. The MIC(50/90) (mg/L) values were as follows: methicillin-susceptible Staphylococcus aureus (MSSA) (0.03/0.25), methicillin-resistant Staphylococcus aureus (MRSA) (1/2), methicillin-susceptible coagulase-negative staphylococci (MSCoNS) (0.03/0.12), methicillin-resistant coagulase-negative staphylococci (MRCoNS) (2/8), Streptococcus pneumoniae (0.016/0.25), viridans group streptococci (0.016/2), β-hemolytic streptococci (≤0.008/≤0.008), Enterococcus faecalis (2/4), Enterococcus faecium (128/>128), Enterobacteriaceae (0.06/0.25), Pseudomonas aeruginosa (0.5/8), Acinetobacter baumannii (0.25/2), Haemophilus influenzae (0.12/0.25), and Moraxella catarrhalis (0.03/0.06). According to the regression curve, the zone diameter breakpoints were 24 and 19 mm for MICs of 1 and 4 mg/L, respectively. This study confirms the potent in vitro activity of doripenem against Pseudomonas aeruginosa, Acinetobacter, Enterobacteriaceae, MSSA, MSCoNS, and respiratory pathogens. According to the EUCAST MIC breakpoints (mg/L) ≤1/>4 for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter, and ≤1/>1 for streptococci, pneumococci, and Haemophilus, the zone diameter breakpoints could be (mm) ≥24/<19 and ≥24/<24, respectively.
    European Journal of Clinical Microbiology 11/2010; 30(4):475-82. · 3.02 Impact Factor
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    ABSTRACT: To determine the proportion of preventable hospital-acquired bloodstream infections (HA-BSIs), the authors prospectively examined consecutive cases in a large university hospital over an 18-month period. Medical charts were assessed with the physician in charge of the patient within 4&emsp14;days after HA-BSI diagnosis to determine whether the infection was healthcare-related. Preventability was assessed using a validated tool. Results of 378 HA-BSIs (incidence rate, 1.00 per 1000 patient-days), 341 were first HA-BSI episodes in a patient, and 272 (79.8%) were secondary to an identifiable source, of whom 196 (57.5%) were related to medical management. These 196 HA-BSIs were related to an invasive procedure (n=163), a non-invasive medical management (n=30) or both (n=3). Of the 272 patients with HA-BSIs from identifiable sources, 55 (20.2%) had no underlying disease, 115 (42.3%) had an ultimately fatal underlying disease, 99 (36.4%) had a rapidly fatal disease, and three (1.1%) were not evaluated. Of the 196 iatrogenic HA-BSIs, 66 were considered preventable (most of them being related to an intravascular catheter), 84 were of uncertain preventability, and 46 were not preventable. In total, 66 of the 341 HA-BSIs (19.4%) were considered preventable, and 191 (56.0%) were not preventable. Although evaluation of the preventability of hospital-associated adverse events has been reported to be difficult and of limited reliability, our simple method may help to identify wards or HA-BSI types that warrant in-depth evaluation.
    Quality and Safety in Health Care 10/2010; 19(5):e30. · 2.16 Impact Factor

Publication Stats

597 Citations
145.59 Total Impact Points

Institutions

  • 2007–2014
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2004–2013
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2003–2013
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
  • 2009
    • University Joseph Fourier - Grenoble 1
      Grenoble, Rhône-Alpes, France