Staphylococcus aureus bloodstream infections: diverging trends of meticillin-resistant and meticillin-susceptible isolates, EU/EEA, 2005 to 2018.

BackgroundInvasive infections caused by Staphylococcus aureus have high clinical and epidemiological relevance. It is therefore important to monitor the S. aureus trends using suitable methods.AimThe study aimed to describe the trends of bloodstream infections (BSI) caused by meticillin-resistant S. aureus (MRSA) and meticillin-susceptible S. aureus (MSSA) in the European Union (EU) and the European Economic Area (EEA).MethodsAnnual data on S. aureus BSI from 2005 to 2018 were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net). Trends of BSI were assessed at the EU/EEA level by adjusting for blood culture set rate (number of blood culture sets per 1,000 days of hospitalisation) and stratification by patient characteristics.ResultsConsidering a fixed cohort of laboratories consistently reporting data over the entire study period, MRSA percentages among S. aureus BSI decreased from 30.2% in 2005 to 16.3% in 2018. Concurrently, the total number of BSI caused by S. aureus increased by 57%, MSSA BSI increased by 84% and MRSA BSI decreased by 31%. All these trends were statistically significant (p < 0.001).ConclusionsThe results indicate an increasing health burden of MSSA BSI in the EU/EEA despite a significant decrease in the MRSA percentage. These findings highlight the importance of monitoring antimicrobial resistance trends by assessing not only resistance percentages but also the incidence of infections. Further research is needed on the factors associated with the observed trends and on their attributable risk.

Fully weekly antituberculosis regimen: a proof-of-concept study.

BACKGROUND: The World Health Organization recommends supervising the treatment of tuberculosis. Intermittent regimens have the potential to simplify the supervision and improve compliance. Our objective was to analyse the sterilising activity of once-weekly regimens based on drugs with a long half-life, bedaquiline and rifapentine, in a murine model of tuberculosis. METHODS: 300 Swiss mice were infected intravenously infected with ×10-6 CFU Mycobacterium tuberculosis H37Rv. Mice were treated once weekly with regimens containing: 1) bedaquiline, rifapentine and pyrazinamide (BPZ); 2) BPZ plus moxifloxacin (BPZM); 3) BPZM plus clofazimine (BPZMC); 4) the standard daily regimen of tuberculosis. All regimens were given for 4 or 6 months. Bactericidal and sterilising activity were assessed. RESULTS: After 2 months of treatment, the mean count in lungs was 0.76±0.60 log10 CFU in mice treated with the daily control regimen and negative in all mice treated with once-weekly regimens (p<0.05 compared to the daily control). All mice had negative lung cultures on completion of either 4 or 6 months of treatment, whereas 3 months after 4 and 6 months of treatment, respectively, the relapse rate was 64% and 13% in the standard daily regimen, 5% and 0% in BPZ, 0% and 0% in BPMZ and 0% and 5% in BPMZC (p<0.05 for all once-weekly regimens versus 4-month daily control; p>0.05 for all once-weekly regimens versus 6-month daily control). CONCLUSIONS: BPZ-based once-weekly regimens have higher sterilising activity than the standard daily regimen and could greatly simplify treatment administration and possibly shorten the duration of tuberculosis treatment.

Poor Performance of Rapid Molecular Tests to Define Eligibility for the Shortcourse Multidrug-resistant Tuberculosis Regimen.

The World Health Organization recommends shortcourse regimen (SCR) to treat multidrug resistant tuberculosis for patients with strains susceptible by line-probe assays (LPAs) to second-line drugs. Our retrospective study shows LPAs have suboptimal specificity in predicting eligibility for SCR; a quarter of eligible patients would receive inadequate therapy with SCR.

Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in Gram-negative species causing bacteraemia, EU/EEA, 2016.

BackgroundAntibiotic resistance, either intrinsic or acquired, is a major obstacle for treating bacterial infections.AimOur objective was to compare the country-specific species distribution of the four Gram-negative species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter species and the proportions of selected acquired resistance traits within these species.MethodWe used data reported for 2016 to the European Antimicrobial Resistance Surveillance Network (EARS-Net) by 30 countries in the European Union and European Economic Area.ResultsThe country-specific species distribution varied considerably. While E. coli accounted for 31.9% to 81.0% (median: 69.0%) of all reported isolates, the two most common intrinsically resistant species P. aeruginosa and Acinetobacter spp. combined (PSEACI) accounted for 5.5% to 39.2% of isolates (median: 10.1%). Similarly, large national differences were noted for the percentages of acquired non-susceptibility to third-generation cephalosporins, carbapenems and fluoroquinolones. There was a strong positive rank correlation between the country-specific percentages of PSEACI and the percentages of non-susceptibility to the above antibiotics in all four species (rho > 0.75 for 10 of the 11 pairs of variables tested).ConclusionCountries with the highest proportion of P. aeruginosa and Acinetobacter spp. were also those where the rates of acquired non-susceptibility in all four studied species were highest. The differences are probably related to national differences in antibiotic consumption and infection prevention and control routines.

Efficiency of different control measures for preventing carbapenemase-producing enterobacteria and glycopeptide-resistant Enterococcus faecium outbreaks: a 6-year prospective study in a French multihospital institution, January 2010 to December 2015.

An infection control programme was implemented in a 21,000-bed multihospital institution for controlling the spread of carbapenemase-producing Enterobacteriaceae (CPE) and glycopeptide-resistant Enterococcus faecium (GRE), classified as 'emergent extensively drug-resistant bacteria' (eXDR) in France. We evaluated factors associated with outbreaks occurrence (n = 103), which followed 901 eXDR introductions (index case followed or not by secondary cases) from 2010 to 2015. In univariate analysis, knowing that patients had been hospitalised abroad, bacterial species (GRE vs CPE, as well as the CPE Klebsiella pneumoniae compared with the other Enterobacteriaceae species) and type of measures implemented within the first 2 days of hospitalisation were associated with outbreaks occurrence, but not the type of wards where carriers were hospitalised, nor the eXDR colonisation or infection status. In multivariate analysis, occurrence of outbreaks was significantly lower when contact precautions (odds ratio (OR): 0.34; 95% confidence interval (CI): 0.22-0.54) and even more when dedicated nursing staff (OR: 0.09; 95% CI: 0.02-0.39) were implemented around eXDR index cases within the first 2 days of hospitalisation (p < 10 - 3). GRE introductions were more frequently associated with occurrence of outbreaks than CPE (OR: 3.58; 95% CI: 2.32-5.51, p < 10 - 3). A sustained and coordinated strategy is efficient to limit the spread of eXDR at the scale of a large health institution.

Molecular Investigation of Resistance to Second-Line Injectable Drugs in Multidrug-Resistant Clinical Isolates of Mycobacterium tuberculosis in France.

The second-line injectable drugs (SLID, i.e., amikacin, kanamycin, capreomycin) are key drugs for the treatment of multidrug-resistant tuberculosis. Mutations in rrs region 1400, tlyA, and eis promoter are associated with resistance to SLID, to capreomycin, and to kanamycin, respectively. In this study, the sequencing data of SLID resistance-associated genes were compared to the results of phenotypic drug susceptibility testing by the proportion method for the SLID in 206 multidrug-resistant clinical isolates of Mycobacterium tuberculosis collected in France. Among the 153 isolates susceptible to the 3 SLID, 145 showed no mutation, 1 harbored T1404C and G1473A mutations in rrs, and 7 had an eis promoter mutation. Among the 53 strains resistant to at least 1 of the SLID, mutations in rrs accounted for resistance to amikacin, capreomycin, and kanamycin for 81%, 75%, and 44% of the isolates, respectively, while mutations in eis promoter were detected in 44% of the isolates resistant to kanamycin. In contrast, no mutations in tlyA were observed in the isolates resistant to capreomycin. The discrepancies observed between the genotypic (on the primary culture) and phenotypic drug susceptibility testing were explained by (i) resistance to SLID with MICs close to the critical concentration used for routine DST and not detected by phenotypic testing (n = 8, 15% of SLID-resistant strains), (ii) low-frequency heteroresistance not detected by sequencing of drug resistance-associated genes on the primary culture (n = 8, 15% of SLID-resistant strains), and (iii) other resistance mechanisms not yet characterized (n = 7, 13% of SLID-resistant strains).

Evaluation of the new GenoType NTM-DR kit for the molecular detection of antimicrobial resistance in non-tuberculous mycobacteria.

Objectives: Non-tuberculous mycobacteria (NTM) are emerging pathogens causing difficult-to-treat infections. We tested a new assay (GenoType NTM-DR) that detects natural and acquired resistance mechanisms to macrolides and aminoglycosides in frequently isolated NTM species. Methods: Performance was assessed on 102 isolates including reference strains [16 Mycobacterium avium , 10 Mycobacterium intracellulare , 8 Mycobacterium chimaera , 15 Mycobacterium chelonae and 53 Mycobacterium abscessus (including subsp. abscessus isolates, 18 with a t28 in erm(41) and 10 with a c28, 13 subsp. bolletii isolates and 12 subsp. massiliense isolates)]. Genotypes were determined by PCR sequencing of erm(41) and rrl for clarithromycin resistance and of the 1400-1480 rrs region for aminoglycoside resistance. Phenotypes were determined by MIC microdilution. Results: GenoType NTM-DR yielded results concordant with Sanger sequencing for 100/102 (98%) isolates. The erm(41) genotypic pattern was accurately identified for M. abscessus isolates . Mutations in rrl were detected in 15 isolates (7 M. avium complex, 5 M. abscessus and 3 M. chelonae ) with acquired clarithromycin resistance harbouring rrl mutations (a2057c, a2058g, a2058t or a2059c). Mutations in rrs were detected in five isolates with amikacin resistance harbouring the rrs mutation a1408g. In two isolates, the NTM-DR test revealed an rrl mutation (initial sequencing being WT), which was confirmed by re-sequencing. The test results were concordant with phenotypic susceptibility testing in 96/102 (94.1%) isolates, with four clarithromycin-resistant and two amikacin-resistant isolates not harbouring mutations. Conclusions: The GenoType NTM-DR test is efficient in detecting mutations predictive of antimicrobial resistance in M. avium complex, M. abscessus and M. chelonae.

Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis?

Background: Moxifloxacin retains partial activity against some fluoroquinolone-resistant mutants of Mycobacterium tuberculosis . Levofloxacin is presumed to be as active as moxifloxacin against drug-susceptible tuberculosis and to have a better safety profile. Objectives: To compare the in vivo activity of levofloxacin and moxifloxacin against M. tuberculosis strains with various levels of fluoroquinolone resistance. Methods: BALB/c mice were intravenously infected with 10 6 M. tuberculosis H37Rv and three isogenic mutants: GyrA A90V, GyrB E540A and GyrB A543V. Treatment with 50 or 100 mg/kg levofloxacin and 60 or 66 mg/kg moxifloxacin was given orally every 6 h, for 4 weeks. Results: Levofloxacin 50 and 100 mg/kg q6h and moxifloxacin 60 and 66 mg/kg q6h generated AUCs in mice equivalent to those of levofloxacin 750 and 1000 mg/day and moxifloxacin 400 and 800 mg/day, respectively, in humans. Moxifloxacin 60 and 66 mg/kg q6h had bactericidal activity against strain H37Rv (MIC ≤ 0.25 mg/L) and mutants GyrB E540A and GyrB A543V (MIC = 0.5 mg/L). Against mutant GyrA A90V (MIC = 2 mg/L), moxifloxacin 60 mg/kg q6h did not prevent bacillary growth, whereas 66 mg/kg q6h had bacteriostatic activity. Levofloxacin 50 mg/kg q6h had bactericidal activity against H37Rv (MIC ≤ 0.25 mg/L) but not against the mutant strains. Levofloxacin 100 mg/kg q6h had bactericidal activity against H37Rv and mutants GyrB E540A (MIC = 0.5 mg/L) and GyrB A543V (MIC= 1 mg/L) but not against mutant GyrA A90V (MIC = 4 mg/L). Conclusions: All mutations reduced fluoroquinolone activity, even those classified as susceptible according to phenotypic tests. High-dose levofloxacin is less effective than high-dose moxifloxacin against both fluoroquinolone-resistant and -susceptible M. tuberculosis strains in mice.

Molecular diagnosis of fluoroquinolone resistance in Mycobacterium tuberculosis.

As a consequence of the use of fluoroquinolones (FQ), resistance to FQ has emerged, leading to cases of nearly untreatable and extensively drug-resistant tuberculosis. Mutations in DNA gyrase represent the main mechanism of FQ resistance. A full understanding of the pattern of mutations found in FQ-resistant (FQ(r)) clinical isolates, and of their proportions, is crucial for improving molecular methods for the detection of FQ resistance in Mycobacterium tuberculosis. In this study, we reviewed the detection of FQ resistance in isolates addressed to the French National Reference Center for Mycobacteria from 2007 to 2012, with the aim of evaluating the performance of PCR sequencing in a real-life context. gyrA and gyrB sequencing, performed prospectively on M. tuberculosis clinical isolates, was compared for FQ susceptibility to 2 mg/liter ofloxacin by the reference proportion method. A total of 605 isolates, of which 50% were multidrug resistant, were analyzed. The increase in FQ(r) strains among multidrug-resistant (MDR) strains during the time of the study was alarming (8% to 30%). The majority (78%) of the isolates with gyrA mutations were FQ(r), whereas only 36% of those with gyrB mutations were FQ(r). Only 12% of the FQ(r) isolates had a single mutation in gyrB. Combined gyrA and gyrB sequencing led to >93% sensitivity for detecting resistance. The analysis of the four false-positive and the five false-negative results of gyrA and gyrB sequencing illustrated the actual limitations of the reference proportion method. Our data emphasize the need for combined gyrA and gyrB sequencing in the investigation of FQ susceptibility in M. tuberculosis and challenge the validity of the current phenotype-based approach as the diagnostic gold standard for determining FQ resistance.

Molecular Analysis of the embCAB Locus and embR Gene Involved in Ethambutol Resistance in Clinical Isolates of Mycobacterium tuberculosis in France.

Modification of codon 306 in embB is regarded as the main mechanism leading to ethambutol (ETB) resistance in clinical isolates of Mycobacterium tuberculosis. However, numerous mutations elsewhere in the embCAB locus and in embR, a putative transcriptional activator of this locus, have been reported to be involved in ETB resistance. Here, we investigated the diversity of nucleotide variations observed in embCAB and embR in M. tuberculosis complex isolates from France. These regions were sequenced in 71 ETB-resistant (ETB-R) and 60 ETB-susceptible (ETB-S) clinical isolates of known phylogenetic lineages. The 131 isolates had 12 mutations corresponding to phylogenetic markers. Among the 60 ETB-S isolates, only 3 (5%) had nonsynonymous mutations that were not phylogenetic markers. Among the 71 ETB-R isolates, 98% had mutations in embCAB that likely contribute to ETB resistance: 70% had mutations located in embB codon 306, 406, or 497; 13% had mutations located outside these three positions between codons 296 and 426; and 15% had mutations corresponding to mutations in the embC-embA intergenic region. We found a strong association between resistance to ETB and the presence of mutations in embB and the embC-embA intergenic region (P < 0.001). In contrast, the mutations detected in embC and embA were not involved in ETB resistance, and no mutation was detected in embR. These results strongly suggest that the sensitivity of diagnostic assays for detecting ETB resistance based on testing of embB codon 306 can be increased by testing of the embB region between codons 296 and 497 and by including the embC-embA intergenic region between positions -8 and -21.

First multicenter study on multidrug resistant bacteria carriage in Chinese ICUs.

BACKGROUND: The importance of multidrug-resistant organisms (MDRO) in Chinese hospitals is not clearly delineated. Thus we sought to assess the prevalence of MDRO in Chinese intensive care units (ICUs). METHODS: Prospective study of inpatients admitted consecutively to eight ICUs in four Chinese cities in 2009-10. Admission and weekly screenings were performed by using selective media for methicillin resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa. For the two latters, resistance to ceftazidime defined MDRO. Backward logistic regression models were designed to assess factors independently associated with MDRO carriage on admission and MDRO acquisition within ICUs. RESULTS: 686 patients were included, and the MDRO prevalence rate on admission was 30.5 % (32.7 % for ESBL-positive Enterobacteriaceae, 3.2 % for MRSA). Antibiotic treatment prior to ICU admission was independently associated with carriage on admission (OR: 1.4) in multivariate analysis. A total of 104 patients acquired ≥1 MDRO in ICU (overall attack rate: 23.7 %; 14.9 % for ESBL-positive Enterobacteriaceae, and 5.1 % for MRSA). The MDRO attack rate increased from 13.2 % in the first week to 82.1 % for ICU stay > 3 weeks. Duration of antibiotic exposure (OR: 1.16; 1.1-1.2) and prior antibiotic treatment before ICU (OR: 2.1; 1.1-3.3) were associated with MDRO acquisition in multivariate analysis. The MDRO prevalence rate on ICU discharge was 51.2 % and the global prevalence density rate 71 per 1000 hospital-days. CONCLUSION: More than one out of two patients was MDRO carrier on ICU discharge in Chinese hospitals. This is the result of the combination of a high MDRO prevalence rate on ICU admission and a high MDRO acquisition rate within ICU.

Could the DiversiLab® semi-automated repetitive-sequence-based PCR be an acceptable technique for typing isolates of Pseudomonas aeruginosa? An answer from our experience and a review of the literature.

Recently the DiversiLab® (DL) system (bioMérieux) was developed as an automated platform that uses repetitive element polymerase chain reaction (rep-PCR) technology for standardized, reproducible DNA fingerprinting of bacteria. The purpose of this study was to evaluate the usefulness of DL rep-PCR for typing Pseudomonas aeruginosa isolates. The performance of DL rep-PCR was compared with that of pulsed-field gel electrophoresis (PFGE) in a prospective multicenter study of patients with ventilator-associated pneumonia due to P. aeruginosa, conducted in 3 intensive care units over a 31-month period. In total, 203 P. aeruginosa isolates from 66 patients, from whom at least 2 consecutive respiratory samples each were collected more than 48 h apart, were typed using DL rep-PCR. Forty isolates (corresponding to 20 patients) were also typed using PFGE of SpeI-digested DNA. The typeability was 100% with DL rep-PCR and 95% with PFGE. The discriminatory power was close for DL rep-PCR and for PFGE (Simpson's diversity indices of 0.901 and 0.947, respectively). Insufficient agreement between DL rep-PCR and PFGE typing results was observed for the 40 selected isolates (adjusted Rand coefficient of 0.419), mostly due to isolates of the same DL rep-PCR type but of different PFGE types (adjusted Wallace coefficients of 0.306 for DL rep-PCR with PFGE, and of 0.667 for PFGE with DL rep-PCR). Considered together with published data, DL rep-PCR results should be interpreted with caution for the investigation of outbreaks caused by P. aeruginosa and evaluated in conjunction with epidemiological data.

Ongoing increasing temporal and geographical trends of the incidence of extended-spectrum beta-lactamase-producing Enterobacteriaceae infections in France, 2009 to 2013.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are a major focus of multidrug-resistant organisms (MRO) surveillance programmes in France. To describe the temporal and geographical trends of these pathogens, we conducted an epidemiological study based on data extracted from the nationwide MRO surveillance network from 2009 to 2013. During this time, the incidence of ESBL-E infections in French hospitals increased by 73%, from 0.35 to 0.60 per 1,000 patient days (PD) (p<0.001) and ESBL-E bacteraemia by 77%, from 0.03 to 0.05 per 1,000 PD (p<0.001). The incidence of ESBL-E infections was higher in intensive-care units (1.62 to 2.44 per 1,000 PD (p<0.001)) than in recovery and long-term care facilities (0.20 to 0.31 per 1,000 PD (p<0.001)). Escherichia coli was the most frequent extended-spectrum beta-lactamase-producing (ESBL) pathogen, representing 59% (26,238/44,425) of all ESBL isolates, followed by Klebsiella pneumoniae (20%; 8,856/44,425) in 2013. The most frequent infection was urinary tract infection, for all species. The incidence of ESBL-E varied by region but showed an upward trend overall. Reinforcement of control measures for halting the spread of such MRO is crucial.

In vivo evaluation of antibiotic activity against Mycobacterium abscessus.

BACKGROUND: The prognosis of Mycobacterium abscessus infections is poor due to the lack of effective drug treatment. The objective of this study was to set up an animal model suitable to test antibiotic activity against M. abscessus. METHODS: The following mouse strains were evaluated: Swiss, BALB/c, C57BL/6, nude, beige, A/J, and GKO. Antibiotic activity was tested for clarithromycin, amikacin, cefoxitin, tigecycline, and bedaquiline (TMC207). Finally, we evaluated the 3-drug combination clarithromycin, cefoxitin, and amikacin. RESULTS: Nude and GKO mice fulfilled criteria for the model but only nude mice offered sufficient availability for large therapeutic experiments. Among the 3 drugs usually combined for treatment of M. abscessus infection, cefoxitin was the most active because it improved survival and reduced bacillary loads in spleen whereas clarithromycin and amikacin prevented death but had little impact on bacillary loads. The triple-drug combination was not more active than cefoxitin alone. Tigecycline displayed bactericidal activity whereas bedaquiline was almost inactive. CONCLUSIONS: Nude mice are an adequate model for in vivo chemotherapy studies. Among tested drugs, cefoxitin and tigecycline showed promising in vivo activity against M. abscessus. The best drug combination remains to be determined.

Imipenem, meropenem, or doripenem to treat patients with Pseudomonas aeruginosa ventilator-associated pneumonia.

Only limited data exist on Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) treated with imipenem, meropenem, or doripenem. Therefore, we conducted a prospective observational study in 169 patients who developed Pseudomonas aeruginosa VAP. Imipenem, meropenem, and doripenem MICs for Pseudomonas aeruginosa isolates were determined using Etests and compared according to the carbapenem received. Among the 169 isolates responsible for the first VAP episode, doripenem MICs were lower (P<0.0001) than those of imipenem and meropenem (MIC50s, 0.25, 2, and 0.38, respectively); 61%, 64%, and 70% were susceptible to imipenem, meropenem, and doripenem, respectively (P was not statistically significant). Factors independently associated with carbapenem resistance were previous carbapenem use (within 15 days) and mechanical ventilation duration before VAP onset. Fifty-six (33%) patients had at least one VAP recurrence, and 56 (33%) died. Factors independently associated with an unfavorable outcome (recurrence or death) were a high day 7 sequential organ failure assessment score and mechanical ventilation dependency on day 7. Physicians freely prescribed a carbapenem to 88 patients: imipenem for 32, meropenem for 24, and doripenem for 32. The remaining 81 patients were treated with various antibiotics. Imipenem-, meropenem-, and doripenem-treated patients had similar VAP recurrence rates (41%, 25%, and 22%, respectively; P=0.15) and mortality rates (47%, 25%, and 22%, respectively; P=0.07). Carbapenem resistance emerged similarly among patients treated with any carbapenem. No carbapenem was superior to another for preventing carbapenem resistance emergence.

Illustration of the difficulty of identifying Streptococcus equi strains at the subspecies level through a case of endocarditis in an immunocompetent man.

We report a case of endocarditis caused by Streptococcus equi in an immunocompetent patient who was subsequently cured after appropriate antibiotherapy and cardiac surgery. However, it was challenging to identify the strain to the subspecies level, which highlights the necessity of developing reliable molecular tools to discriminate between the subspecies.

Rifampicin mono-resistant tuberculosis in France: a 2005-2010 retrospective cohort analysis.

BACKGROUND: Rifampicin resistance is a risk factor for poor outcome in tuberculosis. Therefore, we sought to describe the characteristics and management of Rifampicin monoresistant (RMR) tuberculosis (TB) in France. METHODS: We conducted a retrospective cohort analysis in 2012 on RMR TB patients diagnosed in France between 2005 and 2010 by using a national laboratory network. A standardized questionnaire was used to collect basic demographic data, region of birth, history of TB, HIV-coinfection, alcohol use, and antituberculosis treatment. Outcome was assessed after at least 18 months of follow-up. RESULTS: A total of 39 patients with RMR TB were reported (0.12% of all TB cases). Overall, 19 (49%) had a previous history of treatment, 9 (23%) were HIV-coinfected, and 24 (62%) were smear-positive. Patient with secondary RMR were more likely to have alcohol abuse (P = 0.04) and HIV-coinfection (p = 0.04). Treatment outcome could be assessed for 30 patients, the nine others being dead or lost to follow-up. A total of 20 (67%) of the 30 assessed were cured, 3 (10%) died, 3 (10%) relapsed, and 4 (13%) were lost to follow up. Four (13%) received less than 6 months of treatment, 3 did not have any modification of the standardized regimen, 13 (43%) received fluoroquinolones, 4 (13%) aminoglycosides, and 8 (26%) a combination of both. CONCLUSIONS: RMR TB is a rare disease in France, and its management was heterogeneous. The lack of treatment standardization may be a consequence of low expertise and may lead to the unsatisfactory low success rate.

[Antibiotic resistance: a good example of the "one health" concept]. / L'antibiorésistance : un bon exemple du concept « une seule santé ¼.

Antibiotic resistance is the direct deleterious consequence of two synergistic causes linked to human activity: the massive use of antibiotics in human and animal health, which leads to the selection of the most resistant bacteria, and the spread of these selected resistant bacteria, directly by cross-transmission within human and animal populations and indirectly via the environment. The "one health" concept enables an integrated approach of the various components of the issue, linking human, animal and environmental ecosystems and their dynamics.

La résistance aux antibiotiques est la conséquence délétère directe de deux causes synergiques liées à l'activité humaine : l'utilisation massive d'antibiotiques en santé humaine et animale, qui entraîne la sélection des bactéries les plus résistantes, et la dissémination des bactéries résistantes ainsi sélectionnées, directement par transmission au sein des populations humaines et animales (« transmission croisée ¼), et indirectement via l'environnement. Le concept « une seule santé ¼ permet une approche intégrée des différentes composantes de la question, en permettant de relier les écosystèmes humains, animaux et environnementaux et leurs dynamiques.

Impact of fluoroquinolone resistance on bactericidal and sterilizing activity of a moxifloxacin-containing regimen in murine tuberculosis.

It has been shown previously that fluoroquinolone resistance (defined by resistance to at least 2 mg/liter ofloxacin) has a different impact on moxifloxacin monotherapy depending on the mutation in the sole fluoroquinolone target in Mycobacterium tuberculosis, i.e., DNA gyrase. Since tuberculosis treatment relies on multidrug therapy, we wished to determine the impact of fluoroquinolone resistance on the bactericidal and sterilizing activity of a second-line antituberculous regimen containing moxifloxacin. A total of 280 mice were inoculated with the wild-type Mycobacterium tuberculosis H37Rv strain or one of 3 isogenic fluoroquinolone-resistant mutant strains with increasing moxifloxacin resistance (the GyrB D500N, GyrA A90V, and GyrA D94G strains) and then treated for 6 months with a second-line regimen containing moxifloxacin, pyrazinamide, and ethionamide supplemented with amikacin during the first 2 months. Mice were sacrificed during treatment for measurement of bactericidal activity and 3 months after treatment completion for measurement of relapse rates (sterilizing activity). The CFU counts decreased faster in mice inoculated with the wild type than in mice inoculated with the mutant strains. The relapse rate after treatment completion was different among mice inoculated with mutant strains in relation to the drug resistance level: wild type, 0%; GyrB D500N strain, 33%; GyrA A90V strain, 50%; and GyrA D94G strain, 86%. The relapse rate observed with the GyrB D500N strain was the only one not statistically different from that observed with the wild-type strain. We demonstrated that the impact on sterilizing activity of the most active second-line drug regimen containing moxifloxacin depends on the MIC of moxifloxacin. We suggest that the precise level of moxifloxacin resistance be determined for all strains resistant to 2 mg/liter ofloxacin.

Complete nucleotide sequence of the first KPC-2- and SHV-12-encoding IncX plasmid, pKpS90, from Klebsiella pneumoniae.

We report the complete nucleotide sequence of the pKpS90 plasmid, carrying the bla(KPC-2) and bla(SHV-12) genes. This plasmid was isolated from a sequence type 258 (ST258) Klebsiella pneumoniae strain responsible for an outbreak in a French university hospital in 2009. pKpS90 is a 53,286-bp plasmid that belongs to the IncX incompatibility group. pKpS90 consists of a backbone from IncX plasmids, in which the KPC-2-encoding Tn4401 transposon and a bla(SHV-12)-encoding region have been inserted.