ABSTRACT
SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.
Subject(s)
Advisory Committees/organization & administration , Antitubercular Agents/administration & dosage , Extensively Drug-Resistant Tuberculosis/drug therapy , Tuberculosis, Multidrug-Resistant/drug therapy , Disease Notification , Female , France , Humans , Interdisciplinary Communication , Male , Retrospective StudiesABSTRACT
OBJECTIVES: Carbapenems are among the most powerful antipseudomonal agents. Limited data is available on drug susceptibility testing by routine methods (disc diffusion and Etest) for meropenem and doripenem. We aimed to compare the in vitro activity of imipenem, meropenem, and doripenem against Pseudomonas aeruginosa. METHODS: A total of 311 P. aeruginosa strains isolated from respiratory specimens in 170 patients who developed ventilator-associated pneumonia in two intensive care units were collected over a period of 31 months. The susceptibility of these isolates to imipenem, meropenem, and doripenem were determined by Etest and disc diffusion method. RESULTS: Considering either all isolates or only the first isolates recovered per patient (311 and 170 respectively), the susceptibility rate for doripenem was higher than that for meropenem and imipenem. When MICs determined by Etest were converted into interpretative categories (S, I, R) using French (CA-SFM) guidelines, a poor correlation was observed for meropenem and doripenem. The percentages of correlation with the disc diffusion method were 90.6% and 89.7% for imipenem, 80.5% and 82.6% for meropenem, and 80.5% and 73.3% for doripenem, for the first isolates and all isolates, respectively. The rate of minor errors was as high as 17.7% and 16.1% for meropenem and 17.7% and 25.7% for doripenem for the first isolates and all isolates, respectively. CONCLUSION: The accuracy of disc diffusion using CA-SFM guidelines appears unsatisfactory for all three carbapenems justifying guideline update for P. aeruginosa and carbapenems.
Subject(s)
Carbapenems/pharmacology , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , beta-Lactam Resistance , Disk Diffusion Antimicrobial Tests , Doripenem/pharmacology , Humans , Imipenem/pharmacology , Meropenem/pharmacology , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/microbiology , Practice Guidelines as Topic , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/isolation & purification , Reagent Strips , Sensitivity and SpecificityABSTRACT
SETTINGS: Identification of extensively drug-resistant tuberculosis (XDR-TB) may be delayed because of the lack of availability of molecular testing for second-line drugs (SLDs). Early suspicion of XDR-TB is therefore necessary to avoid developing further drug resistance. OBJECTIVE: To identify the characteristics associated with XDR-TB among multidrug-resistant TB (MDR-TB) cases before the availability of second-line drug susceptibility testing (DST) results. METHODS: All MDR-TB cases with available second-line DST results recorded in France from 1998 to 2013 were classified as simple MDR-TB (no resistance to fluoroquinolones [FQs] or second-line injectable drugs [SLIDs]), pre-XDR-TB (resistance to FQs or SLIDs) and XDR-TB cases (resistance to both). RESULTS: A total of 833 MDR-TB cases were analysed, including 168 (20%) pre-XDR and 62 (7%) XDR-TB cases. A previous history of treatment was acknowledged among 41% of the cases; 12% were human immunodeficiency virus-positive. Characteristics independently associated with XDR-TB were foreign birth (OR 9.5), previous anti-tuberculosis treatment (OR 2.6), smear positivity (OR 4.5) and ethambutol (EMB) resistance (OR 9.1). Characteristics independently associated with pre-XDR-TB compared to simple MDR-TB cases were male sex (OR 1.6), birth in Europe (OR 2.6) and EMB resistance (OR 1.9). CONCLUSION: The presence of clinical or bacteriological characteristics associated with XDR-TB should lead to rapid molecular testing for resistance to SLDs before starting tailored treatment.
Subject(s)
Antitubercular Agents/pharmacology , Extensively Drug-Resistant Tuberculosis/drug therapy , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Adult , Aged , Drug Resistance, Multiple, Bacterial , Extensively Drug-Resistant Tuberculosis/epidemiology , Extensively Drug-Resistant Tuberculosis/microbiology , Female , France/epidemiology , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Risk Factors , Sex Factors , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Young AdultABSTRACT
OBJECTIVE: Molecular methods predict drug resistance several weeks before phenotypic methods and enable rapid implementation of appropriate therapeutic treatment. We aimed to detail the most representative molecular tools used in routine practice for the rapid detection of resistance to antituberculosis drugs among Mycobacterium tuberculosis strains. MATERIALS AND METHODS: The molecular diagnosis of resistance to antituberculosis drugs in clinical samples or from in vitro cultures is based on the detection of the most common mutations in the genes involved in the development of resistance in M. tuberculosis strains (encoding either protein targets of antibiotics, or antibiotic activating enzymes) by commercial molecular kits or by sequencing. RESULTS: Three hypotheses could explain the discrepancies between the genotypic results and the phenotypic drug susceptibility testing results: a low percentage of resistant mutants precluding the detection by genotypic methods on the primary culture; a low level of resistance not detected by phenotypic testing; and other resistance mechanisms not yet characterized. DISCUSSION/CONCLUSIONS: Molecular methods have varying sensitivity with regards to detecting antituberculosis drug resistance; that is why phenotypic susceptibility testing methods are mandatory for detecting antituberculosis drug-resistant isolates that have not been detected by molecular methods. The questionable ability of existing phenotypic and genotypic drug susceptibility testing to properly classify strains as susceptible or resistant, and at what level of resistance, was raised for several antituberculosis agents.
Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , DNA, Bacterial/analysis , Drug Resistance, Bacterial , Genotype , Humans , Microbial Sensitivity Tests , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/genetics , PhenotypeSubject(s)
Bacteremia/complications , HIV Infections/complications , Helicobacter Infections/complications , Adult , Humans , MaleABSTRACT
Fifty-two multidrug-resistant isolates of Mycobacterium tuberculosis representative of the currently predominant lineages in France were analyzed using repetitive-sequence-based PCR (rep-PCR) DiversiLab (DL), spoligotyping, 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing (MIRU-VNTR), and restriction fragment length polymorphism of IS6110 (IS6110-RFLP). DL, as opposed to MIRU-VNTR and IS6110-RFLP analysis, did not allow discrimination among half of the isolates, an indication of comparatively lower resolving power.
Subject(s)
Automation, Laboratory/methods , Molecular Typing/methods , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/genetics , Drug Resistance, Multiple, Bacterial , France , Humans , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
We report here false-positive urinary Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigen test results due to rabbit antilymphocyte serum treatment and provide a simple and fast solution to rule them out by heating urine.
Subject(s)
Antigens, Bacterial/urine , Hot Temperature , Legionella pneumophila/isolation & purification , Legionellosis/diagnosis , Pneumococcal Infections/diagnosis , Specimen Handling/methods , Streptococcus pneumoniae/isolation & purification , Adolescent , Animals , False Positive Reactions , Humans , Male , Urine/chemistry , Urine/microbiologyABSTRACT
The attenuated BCG strain of Mycobacterium bovis is widely used as a vaccine against tuberculosis. However, in rare cases, it can be pathogenic to humans. Here, we report the first draft of a whole-genome sequence of a multidrug-resistant clinical isolate of M. bovis BCG.
Subject(s)
Antigens, Bacterial/cerebrospinal fluid , Chromatography, Affinity , Enterococcus faecalis/immunology , Meningitis, Bacterial/immunology , Streptococcus pneumoniae/immunology , Aged , Amoxicillin/therapeutic use , Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Bacterial Typing Techniques , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Cross Reactions , Delayed Diagnosis , Drug Resistance, Bacterial , Drug Substitution , Drug Therapy, Combination , Endocarditis/complications , Endocarditis/microbiology , Enterococcus faecalis/drug effects , Enterococcus faecalis/isolation & purification , False Positive Reactions , Gentamicins/therapeutic use , Humans , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/etiology , Meningitis, Bacterial/microbiology , Species Specificity , Spinal PunctureABSTRACT
A marked increase in the number of multidrug-resistant (MDR) tuberculosis (TB) cases entirely related to patients born in the Former Soviet Union was observed in France in the last two years. Very few cases were clustered, suggesting it is a consequence of recent immigration of patients already infected in their country of origin. This major increase challenges the existing structures for management of MDR and extensively drug-resistant TB (XDR-TB).
Subject(s)
Extensively Drug-Resistant Tuberculosis/diagnosis , Extensively Drug-Resistant Tuberculosis/ethnology , Mycobacterium tuberculosis/isolation & purification , Patients/statistics & numerical data , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/ethnology , Adult , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Female , France/epidemiology , Genotype , Humans , Incidence , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Risk Factors , Tandem Repeat Sequences , Tuberculosis, Multidrug-Resistant/drug therapy , USSR/ethnology , Young AdultABSTRACT
PCR targeting the gene encoding 16S ribosomal RNA (commonly named broad-range PCR or 16S PCR) has been used for 20 years as a polyvalent tool to study prokaryotes. Broad-range PCR was first used as a taxonomic tool, then in clinical microbiology. We will describe the use of broad-range PCR in clinical microbiology. The first application was identification of bacterial strains obtained by culture but whose phenotypic or proteomic identification remained difficult or impossible. This changed bacterial taxonomy and allowed discovering many new species. The second application of broad-range PCR in clinical microbiology is the detection of bacterial DNA from clinical samples; we will review the clinical settings in which the technique proved useful (such as endocarditis) and those in which it did not (such as characterization of bacteria in ascites, in cirrhotic patients). This technique allowed identifying the etiological agents for several diseases, such as Whipple disease. This review is a synthesis of data concerning the applications, assets, and drawbacks of broad-range PCR in clinical microbiology.
Subject(s)
Bacteriology/trends , Polymerase Chain Reaction/methods , Ribotyping/methods , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , DNA, Bacterial/genetics , DNA, Ribosomal/genetics , False Positive Reactions , Forecasting , Humans , Mass Spectrometry , Polymerase Chain Reaction/economics , Polymerase Chain Reaction/trends , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Ribotyping/economics , Ribotyping/trends , Sensitivity and Specificity , Species SpecificityABSTRACT
Repeated outbreaks of vancomycin-resistant Enterococcus faecium (VRE) occurred between 2004 and 2010 in Assistance Publique--Hôpitaux de Paris (AP-HP), a 23,000-bed multi-hospital institution. From August 2004 to December 2005, the French guidelines for preventing cross-transmission of multiresistant bacteria were applied. Because the number of VRE cases continued to increase, an institutional control programme was implemented from January 2006 onwards: it foresees stopping transfer of VRE and contact patients, separating VRE and contact patients in distinct cohorts, intervention of a central infection control team to support local teams, and quick application of measures as soon as first VRE cases are identified. Between August 2004 and December 2010, 45 VRE outbreaks occurred in 21 of the 38 AP-HP hospitals, comprising 533 cases. Time series analysis showed that the mean number of cases increased by 0.8 cases per month (95% confidence interval (CI): 0.3 to 1.3, p=0.001) before, and decreased by 0.7 cases per month after implementation of the programme (95% CI: -0.9 to -0.5, p<0.001), resulting in a significant trend change of -1.5 cases per month (95% CI: -2.1 to -0.9, p<0.001). The number of cases per outbreak was significantly lower after implementation of the programme. A sustained and coordinated strategy can control emerging bacteria at the level of a large regional multihospital institution.
Subject(s)
Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Enterococcus faecium , Gram-Positive Bacterial Infections/prevention & control , Infection Control/methods , Vancomycin Resistance , Anti-Bacterial Agents/pharmacology , Cross Infection/epidemiology , Cross Infection/microbiology , Electrophoresis, Gel, Pulsed-Field , Enterococcus faecium/drug effects , Enterococcus faecium/genetics , Enterococcus faecium/isolation & purification , France/epidemiology , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Hospital Bed Capacity, 500 and over , Hospitals, Teaching , Humans , Microbial Sensitivity Tests , Practice Guidelines as Topic , Program Evaluation , Prospective Studies , Vancomycin/pharmacologyABSTRACT
OBJECTIVE: To evaluate the impact of an active case-finding programme on tuberculosis (TB) transmission in homeless shelters in Paris, France. DESIGN: Between 1994 and 1997, an active case-finding programme was implemented in homeless shelters using a mobile radiological screening unit, and continued from 1997 to 2007. During these periods, the strains isolated from TB cases diagnosed in the homeless were genotyped by restriction fragment length polymorphism analysis using the insertion sequence IS6110 as a probe. RESULTS: Between 1994 and 2007, 313 new TB cases were diagnosed among the homeless population: 179 through the programme among shelter users, and 134 among homeless people not using shelters. Half of the strains were clustered in 35 distinct patterns (2-48 cases/cluster). The clustering of TB cases steadily decreased in shelters during the 13 years of the survey, from 14.3 to 2.7 related cases per year (P < 0.01) and from 75% to 30% of related cases among all TB cases (P < 0.01). In contrast, there was only a slight trend towards a decrease in homeless people not using shelters. CONCLUSION: Active case finding in homeless shelters resulted in a decrease in case clustering, mainly in shelter users. Genotyping contributed to confirming the positive impact of the intervention.
Subject(s)
Ill-Housed Persons/statistics & numerical data , Mass Screening/methods , Tuberculosis/epidemiology , Cluster Analysis , DNA Fingerprinting , Genotype , Housing/statistics & numerical data , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Paris/epidemiology , Polymorphism, Restriction Fragment Length , Tuberculosis/diagnosis , Tuberculosis/transmissionSubject(s)
Bronchoalveolar Lavage Fluid/microbiology , Coloring Agents , Gentian Violet , Legionella/isolation & purification , Legionellosis/microbiology , Phenazines , Pneumonia, Bacterial/microbiology , Staining and Labeling , Aged, 80 and over , Bacteriological Techniques , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Humans , Legionella/classification , Legionella/genetics , Legionella/growth & development , Macrophages/microbiology , Male , Molecular Sequence Data , Sensitivity and Specificity , Species SpecificityABSTRACT
Non-tuberculous mycobacteria (NTM) infections usually occur in immunocompromised patients but also in immunocompetent patients following invasive procedures, especially for esthetic purposes. Since 2001, 20 episodes (57 cases) of NTM infections, seven of which (43 cases) were related to esthetic care, have been reported to the regional infection control coordinating centers (RICCC), the local health authorities (LHA), and the national institute for public health surveillance. Four notifications (40 cases) were related to non-surgical procedures performed by general practitioners in private settings: mesotherapy, carboxytherapy, and sclerosis of microvaricosities. The three other notifications (three cases) concerned surgical procedures-lifting and mammary prosthesis. Practice evaluations performed by the RICCC and LHA for five notifications showed deficiency of standard hygiene precautions and tap water misuse for injection equipment cleaning, or skin disinfection. Microbiological investigations (national reference center for mycobacteria) demonstrated the similarity of patient and environmental strains: in one episode (16 cases after mesotherapy), M. chelonae isolated from tap water was similar to those isolated from 11 cases. Healthcare-associated NTM infections are rare but have a potentially severe outcome. These cases stress the need of healthcare-associated infection notifications in outpatient settings.
Subject(s)
Cosmetic Techniques/adverse effects , Mycobacterium Infections, Nontuberculous/etiology , Adult , Disease Notification , Disinfection , Equipment Contamination , Female , France/epidemiology , Humans , Hygiene , Male , Mesotherapy/adverse effects , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/transmission , Mycobacterium chelonae/isolation & purification , Nontuberculous Mycobacteria/isolation & purification , Population Surveillance , Postoperative Complications/epidemiology , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/transmission , Sclerotherapy/adverse effects , Water MicrobiologyABSTRACT
Ethionamide (ETH) needs to be activated by the mono-oxygenase EthA, which is regulated by EthR, in order to be active against Mycobacterium tuberculosis. The activated drug targets the enzyme InhA, which is involved in cell wall biosynthesis. Resistance to ETH has been reported to result from various mechanisms, including mutations altering EthA/EthR, InhA and its promoter, the NADH dehydrogenase encoded by ndh, and the MshA enzyme, involved in mycothiol biosynthesis. We searched for such mutations in 87 clinical isolates: 47 ETH-resistant (ETH(r)) isolates, 24 ETH-susceptible (ETH(s)) isolates, and 16 isolates susceptible to ETH but displaying an intermediate proportion of resistant cells (ETH(Sip); defined as ≥1% but <10% resistant cells). In 81% (38/47) of the ETH(r) isolates, we found mutations in ethA, ethR, or inhA or its promoter, which mostly corresponded to new alterations in ethA and ethR. The 9 ETH(r) isolates without a mutation in these three genes (9/47, 19%) had no mutation in ndh, and a single isolate had a mutation in mshA. Of the 16 ETH(Sip) isolates, 7 had a mutation in ethA, 8 had no detectable mutation, and 1 had a mutation in mshA. Finally, of the 24 ETH(s) isolates, 23 had no mutation in the studied genes and 1 displayed a yet unknown mutation in the inhA promoter. Globally, the mechanism of resistance to ETH remained unknown for 19% of the ETH(r) isolates, highlighting the complexity of the mechanisms of ETH resistance in M. tuberculosis.