PubMed Health⌕ Search

Biomedical subjects

V Jarlier

Publications and source records attributed to V Jarlier.

At least 19 recordsLinked to original sources

Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis.

In previous studies, the diarylquinoline R207910 (also known as TMC207) was demonstrated to have high bactericidal activity when combined with first- or second-line antituberculous drugs. Here we extend the evaluation of R207910 in the curative model of murine tuberculosis by assessing the activities of one-, two-, and three-drug combinations containing R207910 and isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or moxifloxacin (MXF) in the setting of a high initial bacillary load (7.2 log(10) CFU). Two months of treatment with the combinations R207910-PZA, R207910-PZA-INH, R207910-PZA-RIF, or R207910-PZA-MXF resulted in culture-negative lung homogenates in 70 to 100% of the mice, while mice treated with INH-RIF-PZA (the reference regimen) or RIF-MXF-PZA remained culture positive. Combinations including R207910 but not PZA (e.g., R207910-INH-RIF and R207910-MXF-RIF) were less active than R207910-PZA-containing regimens administered either alone or with the addition of INH, RIF, or MXF. These results reveal a synergistic interaction between R207910 and PZA. Three-drug combinations containing these two drugs and INH, RIF, or MXF have the potential to significantly shorten the treatment duration in patients, provided that these results can be confirmed in long-term experiments including periods of relapse.

Animals↗

An evaluation of data quality in a network for surveillance of Mycobacterium tuberculosis resistance to antituberculosis drugs in Ile-de-France region-2001-2002.

We evaluated the French Azay-Mycobacteria network for surveillance of Mycobacterium tuberculosis drug resistance by matching data with those collected through the mandatory notification (MNTB). Sensitivity of Azay was 96% by capture-recapture analysis. Cases reported to MNTB were more often smear-positive than non-reported cases. Concordance of data collected for common cases was excellent for a majority of variables (k > 0.79), excepted for tuberculosis site (k = 0.52). These results suggest a good quality of the network.

Antitubercular Agents↗

Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron.

Bacterial Proteins↗

Implementation of isolation precautions: role of a targeted information flyer.

Isolation precautions are advocated in most countries for patients harbouring multi-drug-resistant organisms. We evaluated the impact of a targeted information flyer on the implementation of isolation precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA). A flyer providing a quick reference to the steps to be implemented following detection of MRSA was sent systematically by the microbiologists with all results displaying MRSA. Infection control staff compared isolation precautions in two three-month periods: the first (control) period before implementation of the flyer and the second (intervention) period after implementation of the flyer. Compared with the control period, compliance with isolation precautions increased significantly in the intervention period. In intensive care units, there was a sign posted on the door for 31 of 38 (82%) patients in the control period, and 33 out of 34 (97%) in the intervention period (P=0.06). Use of gowns increased from 82% to 100% (P=0.01), use of dedicated materials increased from 84% to 100% (P=0.03), availability of alcohol hand rub increased from 82% to 94% (P=0.10), and the proportion of MRSA patients in private rooms increased from 71% to 91% of the cases (P=0.07). In conclusion, compliance with isolation precautions increased after attaching a flyer to all MRSA-positive bacteriological results.

Humans↗

Three-year survey of community-acquired methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin in a French university hospital.

A retrospective survey was conducted at Bicêtre Hospital, France from January 2001 to September 2003 to screen for S. aureus isolates with a typical phenotype previously involved in necrotizing pneumonia in France. They were resistant to oxacillin and kanamycin, of intermediate susceptibility to fusidic acid, and susceptible to tobramycin and fluoroquinolones. Seventeen isolates were found and 16 were viable. The Panton-Valentine leukocidin (PVL) genes, various toxin genes and SCCmec IV and agr3 alleles were detected in all isolates. The clonal origin of these isolates was demonstrated by pulsed-field gel electrophoresis. Fourteen isolates were community-acquired methicillin-resistant Staphylococcus (CA-MRSA) isolated from previously healthy patients with skin or soft tissue infections. Three infections were of nosocomial origin, underlining that these PVL-producing CA-MRSA strains may also be hospital acquired. Five CA-MRSA isolates with an identical resistance phenotype collected in a neighbouring teaching hospital (Hôpital Pitié-Salpétrière, Paris, France) were also PVL positive. Three isolates were clonally related to those of the Bicêtre Hospital whereas two were not. This retrospective study identified PVL-producing CA-MRSA in two Parisian hospitals. The incidence at Bicêtre Hospital was 0.8% of all S. aureus and 2% of all MRSA isolated. Our data indicate that these MRSA isolates might become hospital acquired.

Adolescent↗

[Resistance to antituberculous drugs].

Mycobacteria responsible for tuberculosis (M. tuberculosis, M. bovis, M. africanum) are susceptible to a very small number of antibiotics. As soon as these drugs were used in humans all gave rise to the selection of resistant mycobacteria. Study of the mechanisms of acquired resistance, with the help of the genetics of mycobacteria, led to a more accurate understanding of the mode of action of antituberculous drugs. The antibiotics isoniazid, pyrazinamide, ethionamide and ethambutol are mycobacteria-specific because they inhibit the synthesis of mycolic acids, which are specific constituants of the bacterial wall. Mutations responsible for resistance to these drugs affect genes coding for activator enzymes (katg for isoniazid, pncA for pyrazinamide) or genes coding for their target (inhA for isoniazid/ethionamide, embB for ethambutol). With rifamycins, aminosides and quinolones, mechanisms of action and resistance are the same for mycobacteria as for non-mycobacterial organisms. No plasmid or resistance transposon has been described in M. tuberculosis. Currently a test for the quick detection of resistance to rifampicin is widely available but in the future DNA chips may allow the simultaneous detection of multiple resistances. Monitoring of antituberculous drugs shows that in France the prevalence of multiresistance ( resistance to both isoniazid and rifampicin) is 0.5%, primary resistance (before treatment) is 9%, and secondary resistance (after treatment) is 16%.

Antitubercular Agents↗

A case-control study for multidrug-resistant tuberculosis: risk factors in four European countries.

The aim of this study was to detect risk factors for multidrug resistance in patients with pulmonary tuberculosis in four European Union countries: France, Germany, Italy, and Spain. A prospective epidemiological case control study was conducted, made up of patients with clinically diagnosed and microbiologically confirmed pulmonary tuberculosis in the four countries between 1997 and 2000. A total of 138 cases and 276 controls were studied. Considering the four countries as a whole, the most statistically significant risk factors were as follows: intravenous drug use (OR 4.68); asylum-seeker support (OR 2.55) as income factor; living in a nursing home (OR 2.05); previous tuberculosis (OR 2.03) with pulmonary location; prison (OR 2.02); known tuberculosis contacts (OR 2.01); immunosuppression other than human immunodeficiency virus (HIV) (OR 1.96); acquired immunodeficiency syndrome (AIDS) (OR 1.96); current tuberculosis with pulmonary location (OR 1.77); and health-care worker (OR 1.69). These risk factors will have to be taken into account in the European Union as a whole, as well as in each individual country, to establish a health policy of monitoring and control for these cases of multidrug resistance. Although rare, their seriousness makes them particularly important.

Adolescent↗

Efficient intermittent rifapentine-moxifloxacin-containing short-course regimen for treatment of tuberculosis in mice.

Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x10(6) CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.

Animals↗

Cloxacillin versus pristinamycin for superficial pyodermas: a randomized, open-label, non-inferiority study.

BACKGROUND: Superficial pyodermas may require systemic antibiotics. In a previous open-label trial, oxacillin and pristinamycin achieved similar cure rates, but its design was not truly that of a non-inferiority study. OBJECTIVES: To assess the efficacy and safety of oral cloxacillin versus pristinamycin (both 2 g/day) to treat superficial pyodermas. METHODS: Multicentre, parallel-group, open-label, randomized non-inferiority trial. RESULTS: French general practitioners in private practice included 334 out-patients (mean age: 42 years). At the follow-up (day 14), the cure rates (primary efficacy end point) for the intent-to-treat populations were 80.7% (138/171) for cloxacillin and 82.8% (135/163) for pristinamycin. The observed difference between cure rates was -2.1%, with the lower limit of the two-sided 95% confidence interval higher than the non-inferiority threshold of -15%. The per-protocol analysis yielded similar results. Therapy was discontinued for 10 patients (cloxacillin: 1, pristinamycin: 9; p = 0.01). CONCLUSION: Cloxacillin could be an alternative to pristinamycin in out-patients with superficial pyodermas.

Administration, Oral↗

Outbreak of tuberculosis in a migrants' shelter, Paris, France, 2002.

SETTING: An overcrowded 362-bed migrants' shelter in Paris, France. OBJECTIVES: To investigate an outbreak of tuberculosis (TB), to identify a common source of contamination and to prevent further transmission. METHODS: The outbreak was identified by radiographic screening and an active search for undeclared hospital treated cases, completed by strain phenotyping and a search for contact cases. RESULTS: Between October 2001 and October 2002, 56 cases of active TB were identified, 30 by radiological screening and 20 by contacting neighbouring hospitals. All cases involved men, with a median age of 30 years. Pulmonary involvement was present in 54% of cases, and nine patients were sputum smear-positive. Thirty-four of the 37 phenotyped strains clustered together. CONCLUSION: The grouping of the cases in time and place, the large number of cases with early-stage disease and the identical RFLP banding patterns of most of the isolates indicate that this outbreak results from transmission that occurred in France. This report underlines the need for public health departments in industrialised countries to maintain effective anti-tuberculosis control programmes.

Adolescent↗

Incidence of tuberculous meningitis in France, 2000: a capture-recapture analysis.

OBJECTIVE: To estimate the incidence of culture-positive and culture-negative tuberculous meningitis (TBM) in France in 2000. METHODS: Capture-recapture method using two unrelated sources of data: the tuberculosis (TB) mandatory notification system (MNTB), recording patients treated by anti-tuberculosis drugs, and a survey by the National Reference Centre (NRC) for mycobacterial drug resistance, recording culture-positive TBM. RESULTS: Of 112 cases of TBM reported to the MNTB, 28 culture-positive and 34 culture-negative meningitis cases were validated (17 duplicates, 3 cases from outside France, 21 false notifications, and 9 lost records were excluded). The NRC recorded 31 culture-positive cases, including 21 known by the MNTB. When the capture-recapture method was applied to the reported culture-positive meningitis cases, the estimated number of meningitis cases was 41 and the incidence was 0.7 cases per million. Sensitivity was 75.6% for the NRC, 68.3% for the MNTB, and 92.7% for both systems together. When sensitivity of the MNTB for culture-positive cases was applied to culture-negative meningitis, the total estimated number of culture-negative meningitis cases was 50 and the incidence was 0.85 cases per million. CONCLUSION: TBM is underestimated in France. Capture-recapture analysis using different sources to better estimate its incidence is of great interest.

Adult↗

[Descriptive study of bacteremia in a geriatric hospital].

OBJECTIVES: To describe clinical features, microbiologic characteristics and outcome of bacteremia in the elderly patients hospitalized in a geriatric hospital. PATIENTS AND METHODS: All episodes of bacteremia diagnosed from January 1(st) to December 31(st) 1998 were analysed, excluding false-positive cases due to skin contamination. The hospital comprises 1084 geriatric beds distributed as 111 in acute care (ACF), 333 in rehabilitation and intermediate-care (RICF), and 516 in long-term-care facilities (LTCF). RESULTS: Sixty-six episodes of bacteremia were observed in 65 patients. Among them 59 (89%) were nosocomial bacteremia distributed as 20 in ACF, 29 in RICF and 10 in LTCF (rates of 0.6, 0.35, and 0.05 episodes per 1000 patient-days, respectively.). Escherichia coli and Staphylococcus aureus were the main bacterial species involved in 31% and 28% of the cases, respectively. E. coli strains were 50% resistant to amoxicillin and 41% resistant to co-amoxiclav, and 68% of S. aureus strains were resistant to methicillin. Portals of entry were urinary tract (44%), respiratory tract (14%), digestive tract (11%), and soft tissue (8%). The same bacterial strain as in bacteremia was isolated from a peripheric site in 30 cases (47%), most of them being urines. For 15% cases, portal of entry cannot be determined. Mortality associated to nosocomial bacteremia was 25%, and death was significantly associated to MRSA, urinary or intravascular devices, chronic wounds and inappropriate antibiotic prescription. CONCLUSION: In geriatric hospitals, bacteremia are mainly nosocomial cases. Prevention should focus on indwelling devices and antibiotic resistance.

Aged↗

European recommendations for antimicrobial resistance surveillance.

The problem of antimicrobial resistance surveillance in Europe has been debated extensively in many excellent documents issued by national committees that often assume the value of national guidelines. However, a comprehensive document addressing the whole matter from a European perspective, as well as reviewing its present status and drafting future perspectives, has been lacking. The present recommendations have been produced by the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS) through a consensus process involving all members of the Study Group. The recommendations focus on the detection of bacterial resistance and its reporting to clinicians, public health officers and a wider-and ever-increasing-audience. The leading concept is that the basis for resistance monitoring is microbiological diagnostics. The prerequisites for resistance monitoring are findings of adequate quality and quantity, which have been recorded properly and evaluated correctly. Different types of surveillance studies should fulfil different requirements with regard to data collection and reporting, the expected use of data, and the prerequisites for networking such activities. To generate relevant indicators, bacterial resistance data should be reported using adequate denominators and stratification. Reporting of antimicrobial resistance data is necessary for selection of empirical therapy at the local level, for assessing the scale of the resistance problem at the local, national or international levels, for monitoring changes in resistance rates, and for detecting the emergence and spread of new resistances types. Any type of surveillance study should conclude, where appropriate, with a proposal for intervention based on the data obtained.

Anti-Bacterial Agents↗

Use of a high-density DNA probe array for detecting mutations involved in rifampicin resistance in Mycobacterium tuberculosis.

A Mycobacterium high-density DNA probe array designed to detect rpoB mutations conferring rifampicin resistance in Mycobacterium tuberculosis was evaluated. The rpoB hybridisation patterns produced by 41 susceptible (RifS) and 59 rifampicin-resistant (RifR) clinical isolates of M. tuberculosis were compared with the results of conventional dideoxynucleotide sequencing of the rpoB gene. For all the RifR isolates, the rpoB hybridisation patterns correlated with the rpoB sequencing results. Among the 59 isolates, 11 distinct amino-acid changes were detected by the DNA probe array. Of these, 36 (61%) corresponded to replacement of the serine residue found in position 531 (S531L in 34 isolates and S531W in two isolates), 16 (27%) affected histidine 526 (five H526D, five H526Y, four H526L, one H526N and one H526R), four (6.8%) replaced aspartate 516 with a valine, and one (1.7%) replaced glutamine 513 with a leucine. Deletion of the asparagine residue at position 519 was detected in one isolate susceptible to rifampicin, but yielding c. 0.1% resistant colonies on rifampicin-containing medium. No mutation was detected in the rpoB region from one isolate yielding c. 5% of resistant colonies on rifampicin-containing medium. Finally, a D516Y substitution was detected in association with an unexpected mutation, G523W, not tiled on the DNA probe array, but which could be detected by analysing the hybridisation pattern obtained with the wild-type probes covering codon 523. In conclusion, the Mycobacterium probe array is a promising approach to rapid detection of mutations involved in rifampicin resistance in M. tuberculosis.

Amino Acid Substitution↗

Diabetic foot ulcer and multidrug-resistant organisms: risk factors and impact.

AIMS: The primary objective was to characterize factors allowing the colonization of diabetic foot wounds by multidrug-resistant organisms (MDRO), and the secondary objective was to evaluate the influence of MDRO colonization/infection on wound healing. METHODS: In 180 patients admitted to a specialized diabetic foot unit, microbiological specimens were taken on admission. Potential risk factors for MDRO-positive specimens were examined using univariate and multivariate analyses. Prospective follow-up data from 75 patients were used to evaluate the influence of MDRO colonization/infection on time to healing. RESULTS: Eighteen per cent of admission specimens were positive for MDRO. MDRO-positive status was not associated with patient characteristics (age, sex, type of diabetes, complications of diabetes), wound duration, or wound type (neuropathic or ischaemic). In the multivariate analysis, the only factors significantly associated with positive MDRO status on admission were a history of previous hospitalization for the same wound (21/32 compared with 48/148; P = 0.0008) or the presence of osteomyelitis (22/32 compared with 71/148; P = 0.025). In the longitudinal study of 75 wounds, MDRO-positive status on admission or during follow-up (6 months at least or until healing, mean 9 +/- 7 months) was not associated with time to healing (P = 0.71). CONCLUSION: MDROs are often present in severe diabetic foot wounds. About one-third of patients with a history of previous hospitalization for the same wound, and 25% of patients with osteomyelitis, had MDRO-positive specimens. This suggests that hygiene measures, or isolation precautions in the case of admission of patients presenting with these characteristics, should be aggressively implemented to prevent cross-transmission. Positive MDRO status is not associated with a longer time to healing.

Adult↗