-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The incidence of extended-spectrum beta-lactamase producing-enterobacteriacae (ESBL-E) infection is rising worldwide. We aimed to determine the prevalence and nosocomial acquisition rate of ESBL-E as well as the risk factors for ESBL-E carriage and acquisition amongst patients consecutively admitted to 13 internal medicine units at our hospital who were not previously known to be ESBL-E carriers. FINDINGS: We screened all patients admitted or transferred to internal medicine units for ESBL-E on admission and discharge using rectal swabs. Of 1072 patients screened, 51 (4.8%) were carriers of an ESBL-E at admission. Of 473 patients who underwent admission and discharge screening, 21 (4.4%) acquired an ESBL-E. On multivariate analysis, diabetes mellitus without end-organ complications (OR 2.8 [1.1-7.1]), connective tissue disease (OR 7.2 [1.2-44.6], and liver failure (OR 8.4 [1.5-45.4]) were independent risk factors for carriage of an ESBL-E upon admission to hospital (area under the ROC curve, 0.68). Receipt of a first- or second-generation cephalosporin (OR 9.25 [2.2-37.8]), intra-hospital transfer (OR 6.7 [1.7-26.1]), and a hospital stay >21 days (OR 25.1 [4.2-151.7]) were associated with acquisition of an ESBL-E during hospitalisation; whilst admission from home was protective (OR 0.16 [0.06-0.39]) on univariate regression. No risk profile with sufficient accuracy to predict previously unknown carriage on admission or acquisition of ESBL-E could be developed using readily available patient information. CONCLUSIONS: ESBL-E carriage is endemic amongst internal medicine patients at our institution. We were unable to develop a clinical risk profile to accurately predict ESBL-E carriage amongst these patients.
Antimicrobial resistance and infection control. 06/2013; 2(1):20.
-
[show abstract]
[hide abstract]
ABSTRACT: The critical role of non-coding small RNAs (sRNAs) in the bacterial response to changing conditions is increasingly recognized. However, a specific role for sRNAs during antibiotic exposure has not been investigated in S. aureus. Here, we used RNAseq to examine the sRNA response of the multiresistant ST239 S. aureus after exposure to four antibiotics (vancomycin, linezolid, ceftobiprole, and tigecycline) representing the major classes of antimicrobials used to treat methicillin-resistant S. aureus (MRSA) infections. We identified 409 potential sRNAs and then compared global sRNA and mRNA expression profiles at 2 and 6 hours, without antibiotic exposure, and after exposure to each antibiotic, for a vancomycin-susceptible (JKD6009) and a vancomycin-intermediate (JKD6008) strain. Exploration of this dataset by multivariate analysis using a novel implementation of non-negative matrix factorization (NMF) revealed very different responses for mRNA and sRNA. Where mRNA responses clustered with strain or growth phase conditions, the sRNA responses were predominantly linked to antibiotic exposure, including sRNA responses that were specific for particular antibiotics. A remarkable feature of the antimicrobial response was the prominence of antisense sRNAs to genes encoding proteins involved in protein synthesis and ribosomal function. This study has defined a large sRNA repertoire in epidemic ST239 MRSA, and shown for the first time that a subset of sRNAs are part of a coordinated transcriptional response to specific antimicrobial exposures in S. aureus. These data provides a framework for interrogating the role of staphylococcal sRNAs in antimicrobial resistance and exploring new avenues for sRNA-based antimicrobial therapies.
Antimicrobial Agents and Chemotherapy 06/2013; · 4.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Targeted screening of patients at high risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage is an important component of MRSA control programs, which rely on prediction tools to identify those high-risk patients. Most previous risk studies reported a substantial rate of patients who are eligible for screening, but failed to be enrolled. The characteristics of these missed patients are seldom described. We aimed to determine the rate and characteristics of patients who were missed by a MRSA screening programme at our institution to see how the failure to include these patients might impact the accuracy of clinical prediction tools. FINDINGS: From March-June 2010 all patients admitted to 13 internal medicine wards at the University of Geneva Hospital (HUG) were prospectively screened for MRSA carriage. Of 1968 patients admitted to the ward, 267 patients (13.6%) failed to undergo appropriate MRSA screening. Forty-one (2.4%) screened patients were MRSA carriers at admission. On multivariate regression, patients who were missed by screening were more likely to be aged < 50 years (OR 2.4 [1.4-3.9]), transferred to internal medicine from another ward in the hospital (OR 2.8 [1.1-7.1]), and have a history of malignancy (OR 3.2[2.1-5.1]). There was no significant difference in the rate of previous MRSA carriage between screened and unscreened patients. CONCLUSIONS: Our findings highlight the potential bias that "missed" patients may introduce into MRSA risk scores. Reporting on the proportions and characteristics of missed patients is essential for accurate interpretation of MRSA prediction tools.
Antimicrobial resistance and infection control. 05/2013; 2(1):17.
-
Benedikt Huttner,
Thomas Haustein,
Ilker Uçkay,
Gesuele Renzi,
Andrew Stewardson,
Danièle Schaerrer,
Americo Agostinho,
Antoine Andremont, Jacques Schrenzel,
Didier Pittet,
Stephan Harbarth
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES: Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasingly frequent cause of infections in the community and the healthcare setting. In this study, we aimed to investigate whether intestinal carriage of ESBL-E can be eradicated. METHODS: We conducted a double-blind, randomized, placebo-controlled, single-centre trial to assess the efficacy of an oral decolonization regimen on intestinal ESBL-E carriage in adult patients with an ESBL-E-positive rectal swab. Fifty-eight patients were allocated 1 : 1 to either placebo or colistin sulphate (50 mg 4×/day) and neomycin sulphate (250 mg 4×/day) for 10 days plus nitrofurantoin (100 mg 3×/day) for 5 days in the presence of ESBL-E bacteriuria. The primary outcome was detection of ESBL-E by rectal swab 28 ± 7 days after the end of treatment. Missing primary outcome data were imputed based on the last available observation. Additional cultures (rectal, inguinal and urine) were taken on day 6 of treatment and on days 1 and 7 post-treatment. The study protocol has been registered with ClinicalTrials.gov (NCT00826670). RESULTS: Among 54 patients (27 in each group) included in the primary analysis, there was no statistically significant difference between the groups with regard to the primary outcome [14/27 (52%) versus 10/27 (37%), P = 0.27]. During treatment and shortly afterwards, there was significantly lower rectal ESBL-E carriage in the treatment group: 9/26 versus 19/22 on day 6 of treatment (P < 0.001) and 8/25 versus 20/26 on day 1 post-treatment (P = 0.001). This effect had disappeared by day 7 post-treatment (18/27 versus 17/25, P = 0.92). Liquid stools were more common in the treatment group (7/27 versus 2/29, P = 0.05). CONCLUSIONS: The regimen used in this study temporarily suppressed ESBL-E carriage, but had no long-term effect.
Journal of Antimicrobial Chemotherapy 05/2013; · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Bacteria are faced with a diversity of environmental stresses that include high salt concentrations, heavy metals and pH fluctuations. Adaptation to resist such stresses is a complex phenomenon that involves global pathways and simultaneous acquisition of multiple unrelated properties. During the last 3 years, the development of new technologies in the field of molecular biology has led to numerous fundamental and quantitative in vitro and in vivo evolutionary studies that have improved our understanding of the principles underlying bacterial adaptations, and helped us develop strategies to cope with the health burden of bacterial virulence. In this review, the authors discuss the evolution of bacteria in the laboratory and in human patients.
Future Microbiology 05/2013; 8:661-74. · 3.82 Impact Factor
-
Journal of Integrated OMICS. 02/2013; 1:28-35.
-
[show abstract]
[hide abstract]
ABSTRACT: Kingella kingae is a Gram-negative bacterium that is today recognized as the major cause of joint and bone infections in young children. This microorganism is a member of the normal flora of the oropharynx, and the carriage rate among children under 4 years of age is approximately 10%. K. kingae is transmitted from child to child through close personal contact. Key virulence factors of K. kingae include expression of type IV pili, Knh-mediated adhesive activity and production of a potent RTX toxin. The clinical presentation of K. kingae invasive infection is often subtle and may be associated to mild-to-moderate biologic inflammatory responses, highlighting the importance a high index of suspicion. Molecular diagnosis of K. kingae infections by nucleic acid amplification techniques enables identification of this fastidious microorganism. Invasive infections typically respond favorably to medical treatment, with the exception of cases of endocarditis, which may require urgent valve replacement.
Future Microbiology 02/2013; 8:233-45. · 3.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective. To obtain an unbiased estimate of the excess hospital length of stay (LOS) and cost attributable to extended-spectrum β-lactamase (ESBL) positivity in bloodstream infections (BSIs) due to Enterobacteriaceae. Design. Retrospective cohort study. Setting. A 2,200-bed academic medical center in Geneva, Switzerland. Patients. Patients admitted during 2009. Methods. We used multistate modeling and Cox proportional hazards models to determine the excess LOS and adjusted end-of-LOS hazard ratio (HR) for ESBL-positive and ESBL-negative BSI. We estimated economic burden as the product of excess LOS and average bed-day cost. Patient-level accounting data provided a complementary analysis of economic burden. A predictive model was fitted to national surveillance data. Results. Thirty ESBL-positive and 96 ESBL-negative BSI cases were included. The excess LOS attributable to ESBL-positive and ESBL-negative BSI was 9.4 (95% confidence interval [CI], 0.4-18.4) and 2.6 (95% CI, 0.7-5.9) days, respectively. ESBL positivity was therefore associated with 6.8 excess days and CHF 9,473 per BSI. The adjusted end-of-LOS HRs for ESBL-positive and ESBL-negative BSI were 0.62 (95% CI, 0.43-0.89) and 0.90 (95% CI, 0.74-1.10), respectively. After reimbursement, the average financial loss per acute care episode in ESBL-positive BSI, ESBL-negative BSI, and control cohorts was CHF 48,674, 48,131, and 13,532, respectively. Our predictive model estimated that the nationwide cost of third-generation cephalosporin resistance would increase from CHF 2,084,000 in 2010 to CHF 3,526,000 in 2015. Conclusions. This is the first hospital-wide analysis of excess LOS attributable to ESBL positivity determined using multistate modeling to avoid time-dependent bias. These results may inform health-economic evaluations of interventions targeting ESBL control.
Infection Control and Hospital Epidemiology 02/2013; 34(2):133-43. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Streptococcus tigurinus, a novel member of the Streptococcus mitis group, was recently identified as a causative agent of invasive infections. We report the complete genome sequences of the S. tigurinus type strain AZ_3a and S. tigurinus strain 1366. The genome sequences assist in the characterization of virulence determinants of S. tigurinus.
Genome announcements. 01/2013; 1(2).
-
[show abstract]
[hide abstract]
ABSTRACT: Colonization of the oropharynx by Kingella kingae is currently considered to be a pre-requisite for later development of invasive infections. However, the oropharyngeal K kingae DNA bacterial load (DBL) in children with osteoarticular infections caused by this microorganism is not different than that of asymptomatic carriers.
The Pediatric Infectious Disease Journal 12/2012; · 3.58 Impact Factor
-
Cindy Lamamy,
Aline Berthelot,
Xavier Bertrand,
Anne-Sophie Valentin,
Sandra Dos Santos,
Sophie Thiais,
Virginie Morange,
Nicole Girard,
Pierre-Yves Donnio,
Roland Quentin, Jacques Schrenzel,
Patrice François,
Nathalie van der Mee-Marquet
[show abstract]
[hide abstract]
ABSTRACT: We report four bloodstream infections associated with CC9 agr type II S. aureus in patients without animal exposure. We demonstrate, by microarray analysis, the presence of egc cluster, fnbA, cap operon, lukS, set2, set12, splE, splD, sak, epiD and can, genomic features associated with a high virulence potential in humans.
Clinical Infectious Diseases 12/2012; · 9.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE:The purpose of this study was to investigate if oropharyngeal swab polymerase chain reaction (PCR) could predict osteoarticular infection (OAI) due to Kingella kingae in young children.METHODS:One hundred twenty-three consecutive children aged 6 to 48 months presenting with atraumatic osteoarticular complaints were prospectively studied. All had a clinical evaluation, imaging, and blood samples. Blood and oropharyngeal specimens were tested with a PCR assay specific for K kingae. OAI was defined as bone, joint, or blood detection of pathogenic bacteria, or MRI consistent with infection in the absence of positive microbiology. K kingae OAI was defined by blood, bone, or synovial fluid positivity for the organism by culture or PCR.RESULTS:Forty children met the OAI case definition; 30 had K kingae OAI, 1 had another organism, and 9 had no microbiologic diagnosis. All 30 oropharyngeal swabs from the K kingae case patients and 8 swabs from the 84 patients without OAI or with OAI caused by another organism were positive. The sensitivity and specificity of the oropharyngeal swab PCR assay for K kingae were 100% and 90.5%, respectively.CONCLUSIONS:Detection of K kingae DNA in oropharyngeal swabs of children with clinical findings of OAI is predictive of K kingae OAI. If these findings are replicated in other settings, detection of K kingae by oropharyngeal swab PCR could improve the recognition of OAI.
PEDIATRICS 12/2012; · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Background: Surgical site infections (SSIs) after colorectal surgery usually are caused by commensal intestinal bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) may be responsible for additional SSI-related morbidity. The aim of this retrospective cohort study was to describe the epidemiology of SSIs caused by MRSA after colorectal surgery in two tertiary-care centers, one in Geneva, Switzerland (G), and the other in Chicago, Illinois (C). Methods: Adult patients undergoing colorectal resections during periods of universal screening for MRSA on admission were identified retrospectively. Demographic characteristics, surgery-related factors, and occurrence of MRSA SSI were compared in patients with and without MRSA carriage before surgery. Results: There were 1,069 patients (G=194, C=875) with a median age of 67 years fulfilling the inclusion criteria. Of these, 45 patients (4.2%) had a positive MRSA screening result within 30 days before surgery (G=18, C=27; p<0.001). Ten patients (0.9%; G=6, C=4) developed MRSA SSI, detected a median of 17.5 days after surgery, but only two of them were MRSA-positive before surgery. Nine of the 45 MRSA carriers identified by screening received pre-operative prophylaxis with vancomycin (G 6/18, C 3/27), and 17 of these patients (37.8%; G 7/18, C 10/27) were started on MRSA decolonization therapy before surgery. Pre-operative administration of either decolonization or vancomycin was not protective against MRSA SSI (p=0.49). Conclusion: Methicillin-resistant S. aureus seems to be an infrequent cause of SSI after colorectal resections, even in MRSA carriers. Systematic universal screening for MRSA carriage prior to colorectal surgery may not be beneficial for the individual patient. Post-operative factors seem to be important in MRSA infections, as the majority of MRSA SSIs occurred in patients negative for MRSA carriage.
Surgical Infections 12/2012; · 1.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: DEAD-box RNA helicases are present in almost all living organisms and participate in various processes of RNA metabolism. Bacterial proteins of this large family were shown to be required for translation initiation, ribosome biogenesis and RNA decay. The latter is primordial for rapid adaptation to changing environmental conditions. In particular, the RhlB RNA helicase from E. coli was shown to assist the bacterial degradosome machinery. Recently, the CshA DEAD-box proteins from Bacillus subtilis and Staphylococcus aureus were shown to interact with proteins that are believed to form the degradosome. S. aureus can cause life-threatening disease, with particular concern focusing on biofilm formation on catheters and prosthetic devices, since in this form the bacteria are almost impossible to eradicate both by the immune system and antibiotic treatment. This persistent state relies on the expression of surface encoded proteins that allow attachment to various surfaces, and contrasts with the dispersal mode of growth that relies on the secretion of proteins such as hemolysins and proteases. The switch between these two states is mainly mediated by the Staphylococcal cell density sensing system encoded by agr. We show that inactivation of the cshA DEAD-box gene results in dysregulation of biofilm formation and hemolysis through modulation of agr mRNA stability. Importantly, inactivation of the agrA gene in the cshA mutant background reverses the defect, indicating that cshA is genetically upstream of agr and that a delicate balance of agr mRNA abundance mediated through stability control by CshA is critical for proper expression of virulence factors.
RNA biology 12/2012; 10(1). · 5.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The stringent response is initiated by rapid (p)ppGpp synthesis, which leads to a profound reprogramming of gene expression in most bacteria. The stringent phenotype seems to be species specific and may be mediated by fundamentally different molecular mechanisms. In Staphylococcus aureus, (p)ppGpp synthesis upon amino acid deprivation is achieved through the synthase domain of the bifunctional enzyme RSH (RelA/SpoT homolog). In several firmicutes, a direct link between stringent response and the CodY regulon was proposed. Wild-type strain HG001, rsh(Syn), codY and rsh(Syn), codY double mutants were analyzed by transcriptome analysis to delineate different consequences of RSH-dependent (p)ppGpp synthesis after induction of the stringent response by amino-acid deprivation. Under these conditions genes coding for major components of the protein synthesis machinery and nucleotide metabolism were down-regulated only in rsh positive strains. Genes which became activated upon (p)ppGpp induction are mostly regulated indirectly via de-repression of the GTP-responsive repressor CodY. Only seven genes, including those coding for the cytotoxic phenol-soluble modulins (PSMs), were found to be up-regulated via RSH independently of CodY. qtRT-PCR analyses of hallmark genes of the stringent response indicate that an RSH activating stringent condition is induced after uptake of S. aureus in human polymorphonuclear neutrophils (PMNs). The RSH activity in turn is crucial for intracellular expression of psms. Accordingly, rsh(Syn) and rsh(Syn), codY mutants were less able to survive after phagocytosis similar to psm mutants. Intraphagosomal induction of psmα1-4 and/or psmβ1,2 could complement the survival of the rsh(Syn) mutant. Thus, an active RSH synthase is required for intracellular psm expression which contributes to survival after phagocytosis.
PLoS Pathogens 11/2012; 8(11):e1003016. · 9.13 Impact Factor
-
Damien Bouchard,
Vincent Peton,
Sintia Almeida,
Caroline Le Maréchal,
Anderson Miyoshi,
Vasco Azevedo,
Nadia Berkova,
Lucie Rault,
Patrice François, Jacques Schrenzel,
Sergine Even,
David Hernandez,
Yves Le Loir
[show abstract]
[hide abstract]
ABSTRACT: Staphylococcus aureus is a major etiological agent of mastitis in ruminants. We report here the genome sequence of bovine strain Newbould 305, isolated in the 1950s in a case of bovine mastitis and now used as a model strain able to reproducibly induce chronic mastitis in cows.
Journal of bacteriology 11/2012; 194(22):6292-3. · 3.94 Impact Factor
-
International journal of antimicrobial agents 10/2012; · 3.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: New DNA sequencing technologies have emerged in the last decade enabling in-depth study of human gut microbiota. The bacterial communities inhabiting the gut inBuence our immune development and maturation with consequences for general health. However, the balance between host and bacterial community is a5ected by changes in lifestyle. Increasing rates of caesarean delivery, formula-feeding, antibiotic treatments, high fat diet, urbanization and hygiene have led to important changes in the colonization of the gut microbiota. Emergent diseases and conditions including asthma, allergies, autoimmunity, necrotizing enterocolitis (NEC), obesity and type I diabetes may be related to modifications in the microbiota. In this review we focus on studies related to early bacterial colonization of the gut, and how the evolution of gut microbiota during the :rst years of life may lead to new perspectives on the treatment of these diseases. Diet complementation with preor probiotics in formula or replacement of a disease associated-microbiota with a healthy one are currently the most studied approaches in the treatment of microbiota-related disorders. Bacteriophages may provide an alternative means for manipulating gut bacterial communities. However, the question is whether we can alter infant gut microbiota without any risk to health. High-throughput sequencing (HTS) techniques give access to the composition of the gut microbiome, and its evolution over time or in response to di5erent circumstances. This review discusses these techniques, evaluates the impact of microbiome composition on infant development and outlines possible improvements in health care based on this knowledge.
Journal of Integrated OMICS. 05/2012; Vol 2(No 1):1-16.
-
[show abstract]
[hide abstract]
ABSTRACT: Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection.
Critical care (London, England) 05/2012; 16(3):222. · 4.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to evaluate the absolute risk for children younger than 4 years of age with asymptomatic oropharyngeal carriage of Kingella kingae to sustain an osteoarticular infection. The rate of K. kingae carriage in the oropharyngeal mucosa was 9% among healthy children, and the risk for an asymptomatic carrier to develop an osteoarticular infection due to K. Kingae was estimated to be lower than 1%.
The Pediatric Infectious Disease Journal 05/2012; 31(9):983-5. · 3.58 Impact Factor
