RESUMEN
From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.
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Brotes de Enfermedades , Inmunoglobulina M , Infecciones por Parvoviridae , Parvovirus B19 Humano , Humanos , Francia/epidemiología , Parvovirus B19 Humano/aislamiento & purificación , Adulto , Femenino , Masculino , Niño , Infecciones por Parvoviridae/epidemiología , Infecciones por Parvoviridae/diagnóstico , Inmunoglobulina M/sangre , Adolescente , Preescolar , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Eritema Infeccioso/epidemiología , Eritema Infeccioso/diagnóstico , Adulto Joven , Lactante , AncianoRESUMEN
PURPOSE OF REVIEW: The first studies on COVID-19 patients with acute respiratory distress syndrome (ARDS) described a high rate of secondary bacterial ventilator-associated pneumonia (VAP). The specificity of VAP diagnoses in these patients are reviewed, including their actual rate. RECENT FINDINGS: Published studies described high rates of bacterial VAP among COVID-19 patients with ARDS, and these VAP episodes are usually severe and of specifically poor prognosis with high mortality. Indeed, Severe acute respiratory syndrome - coronavirus disease 19 (SARS-CoV2) infection elicits alterations that may explain a high risk of VAP. In addition, breaches in the aseptic management of patients might have occurred when the burden of care was heavy. In addition, VAP in these patients is more frequently suspected, and more often investigated with diagnostic tools based on molecular techniques. SUMMARY: VAP is frequented and of particularly poor prognosis in COVID-19 patients with ARDS. It can be explained by SARS-CoV-2 pathophysiology, and also breaches in the aseptic procedures. In addition, tools based on molecular techniques allow an early diagnosis and unmask VAP usually underdiagnosed by traditional culture-based methods. The impact of molecular technique-based diagnostics in improving antibacterial therapy and COVID-19 prognosis remain to be evaluated.
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COVID-19 , Neumonía Asociada al Ventilador , Humanos , Neumonía Asociada al Ventilador/diagnóstico , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/microbiología , ARN Viral , Respiración Artificial , SARS-CoV-2RESUMEN
PURPOSE OF REVIEW: We conducted a systematic review of the literature to update findings on the epidemiology and the management of cerebral abscesses in immunocompetent patients. RECENT FINDINGS: Observational studies suggest that the overall prognosis has improved over the last decades but mortality rates remain high. Several parameters may contribute to a better prognosis, including the identification of common risk factors for brain abscess, the systematic use of brain MRI at diagnosis, the implementation of appropriate neurosurgical and microbiological techniques for diagnosis, the optimization of the antibacterial treatment based on epidemiology and pharmacokinetic/pharmacodynamic studies, and a long-term follow-up for detection of secondary complications. Outcome research on brain abscess is mainly based on observational studies. Randomized controlled trials have yet to be performed to identify clinically relevant interventions associated with improved patient-centered outcomes. SUMMARY: Our review highlights the importance of a multidisciplinary approach to optimize brain abscess management both at the acute phase and in the long-term. Randomized controlled studies are urgently needed to identify interventions associated with improved outcomes.
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Absceso Encefálico , Antibacterianos/uso terapéutico , Absceso Encefálico/diagnóstico , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Evaluación de Resultado en la Atención de SaludRESUMEN
Because the diagnosis of co/superinfection in COVID-19 patients is challenging, empirical antibiotic therapy is frequently initiated until microbiological analysis results. We evaluated the performance and the impact of the BioFire® FilmArray® Pneumonia plus Panel on 112 respiratory samples from 67 COVID-19 ICU patients suspected of co/superinfections. Globally, the sensitivity and specificity of the test were 89.3% and 99.1%, respectively. Positive tests led to antibiotic initiation or adaptation in 15% of episodes and de-escalation in 4%. When negative, 28% of episodes remained antibiotic-free (14% no initiation, 14% withdrawal). Rapid multiplex PCRs can help to improve antibiotic stewardship by administering appropriate antibiotics earlier and avoiding unnecessary prescriptions.
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Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Infecciones Bacterianas/tratamiento farmacológico , COVID-19/complicaciones , Reacción en Cadena de la Polimerasa Multiplex/métodos , Anciano , Programas de Optimización del Uso de los Antimicrobianos , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , COVID-19/virología , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/fisiologíaRESUMEN
BACKGROUND: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). METHODS: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. RESULTS: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care. CONCLUSIONS: Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia.
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Antiinfecciosos/administración & dosificación , Reacción en Cadena de la Polimerasa Multiplex/métodos , Neumonía/tratamiento farmacológico , Factores de Tiempo , Adulto , Antiinfecciosos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/fisiopatología , Estudios RetrospectivosRESUMEN
Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.).
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Antibacterianos/uso terapéutico , Cefotaxima/farmacología , Ceftriaxona/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Adolescente , Adulto , Cefalosporinas/uso terapéutico , Heces , Femenino , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/efectos de los fármacos , Adulto JovenRESUMEN
To get insights into the temporal pattern of commensal Escherichia coli populations, we sampled the feces of four healthy cows from the same herd in the Hwange District of Zimbabwe daily over 25 days. The cows had not received antibiotic treatment during the previous 3 months. We performed viable E. coli counts and characterized the 326 isolates originating from the 98 stool samples at a clonal level, screened them for stx and eae genes, and tested them for their antibiotic susceptibilities. We observed that E. coli counts and dominant clones were different among cows, and very few clones were shared. No clone was shared by three or four cows. Clone richness and evenness were not different between cows. Within each host, the variability in the E. coli count was evidenced between days, and no clone was found to be dominant during the entire sampling period, suggesting the existence of clonal interference. Dominant clones tended to persist longer than subdominant ones and were mainly from phylogenetic groups A and B1. Five E. coli clones were found to contain both the stx1 and stx2 genes, representing 6.3% of the studied isolates. All cows harbored at least one Shiga toxin-producing E. coli (STEC) strain. Resistance to tetracycline, penicillins, trimethoprim, and sulfonamides was rare and observed in three clones that were shed at low levels in two cows. This study highlights the fact that the commensal E. coli population, including the STEC population, is host specific, is highly dynamic over a short time frame, and rarely carries antibiotic resistance determinants in the absence of antibiotic treatment.IMPORTANCE The literature about the dynamics of commensal Escherichia coli populations is very scarce. Over 25 days, we followed the total E. coli counts daily and characterized the sampled clones in the feces of four cows from the same herd living in the Hwange District of Zimbabwe. This study deals with the day-to-day dynamics of both quantitative and qualitative aspects of E. coli commensal populations, with a focus on both Shiga toxin-producing E. coli and antibiotic-resistant E. coli strains. We show that the structure of these commensal populations was highly specific to the host, even though the cows ate and roamed together, and was highly dynamic between days. Such data are of importance to understand the ecological forces that drive the dynamics of the emergence of E. coli clones of particular interest within the gastrointestinal tract and their transmission between hosts.
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Bovinos/microbiología , Escherichia coli/fisiología , Animales , Bovinos/fisiología , Escherichia coli/clasificación , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Heces/microbiología , Filogenia , Toxina Shiga/genética , Toxina Shiga/metabolismo , Simbiosis , ZimbabweRESUMEN
A total of 458 patients were prospectively included at hospital admission and screened for extended-spectrum-beta-lactamase-producing (ESBL) Escherichia coli carriage in 2007 and in 2010 to 2012. A 4-fold increase in ESBL carriage (3% to 12%), a 5-fold increase in numbers of community patients among ESBL carriers, and a higher number of multiple ESBL strains was found in the 2010 to 2012 period. ESBL E. coli represented the dominant E. coli strain (relative abundance, >50%) in 10/32 (31%) of ESBL carriers. This represents a major threat in terms of infectious risk and dissemination.
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Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Microbioma Gastrointestinal , beta-Lactamasas/genética , Anciano , Carga Bacteriana , Portador Sano , Femenino , Francia , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The ability to capture iron is a challenge for most bacteria. The neonatal meningitis Escherichia coli strain S88 possesses several iron uptake systems, notably including siderophores. Transcriptional analysis of the ColV plasmid pS88 has shown strong induction of a previously undescribed gene with low identity to three E. coli chromosomal genes encoding phospho-2-dehydro-3-deoxyheptonate aldolases involved in aromatic amino acid and catecholate/phenolate siderophore biosynthesis through the shikimate pathway. Here, we investigated the role of this gene, ssbLp (ssbL carried on the plasmid), in siderophore biosynthesis and, consequently, in S88 virulence. We constructed an S88 mutant designated S88 ΔssbLp, which exhibited reduced growth under low-iron conditions compared to the wild-type strain. Liquid chromatography-mass spectroscopy analysis of culture supernatants showed that the mutant secreted significantly smaller amounts of enterobactin, salmochelin SX, and yersiniabactin than the wild-type strain. The mutant was also less virulent in a neonatal rat sepsis model, with significantly lower bacteremia and mortality. Supplementation with chorismate, the final product of the shikimate pathway, restored the wild-type phenotype in vitro. In a collection of human extraintestinal E. coli isolates, we found that ssbL was present only in strains harboring the iro locus, encoding salmochelins, and was located either on the chromosome or on plasmids. Acquisition of the iro locus has been accompanied by acquisition of the auxiliary gene ssbL, which boosts the metabolic pathway essential for catecholate/phenolate siderophore biosynthesis and could represent potential therapeutic targets.
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Aldehído-Liasas/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Meningitis por Escherichia coli/microbiología , Plásmidos/genética , Ácido Shikímico/metabolismo , Sideróforos/biosíntesis , Factores de Virulencia/metabolismo , Aldehído-Liasas/genética , Animales , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Humanos , Hierro/metabolismo , Redes y Vías Metabólicas , Plásmidos/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the ß-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience. RESULTS: While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of ß-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the ß-lactamase activity of the microbiota. The level of ß-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools. CONCLUSIONS: In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous ß-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon. Video Abstract.
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Microbioma Gastrointestinal , Resiliencia Psicológica , Adulto , Humanos , Microbioma Gastrointestinal/genética , beta-Lactamasas/genética , beta-Lactamas/farmacología , Voluntarios Sanos , Antibacterianos , Bacterias/genética , Heces/microbiologíaRESUMEN
We investigated mechanisms of the false-positive test results on rapid-antigen detection test (RADT) for group A Streptococcal (GAS) pharyngitis. Most RADT false-positives (76%) were associated with polymerase chain reaction-positive GAS results, suggesting that RADT specificity could be considered close to 100%. Finding that 61% of GAS culture-negative but RADT-positive cases were positive on both GAS polymerase chain reaction and Staphylococcus aureus testing, we posit bacterial inhibition as causative.
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Antígenos Bacterianos/análisis , Faringitis/diagnóstico , Faringe/microbiología , Staphylococcus aureus/aislamiento & purificación , Infecciones Estreptocócicas/diagnóstico , Streptococcus pyogenes/aislamiento & purificación , Adolescente , Antígenos Bacterianos/genética , Estudios de Casos y Controles , Niño , Preescolar , Reacciones Falso Positivas , Humanos , Faringitis/microbiología , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad , Staphylococcus aureus/inmunología , Streptococcus pyogenes/inmunologíaRESUMEN
Cefiderocol (FDC) is a siderophore cephalosporin now recognized as a new weapon in the treatment of difficult-to-treat-resistant (DTR) Gram-negative pathogens, including carbapenemase-producing enterobacterales and non-fermentative Gram-negative bacilli (GNB). This article reports our experience with an FDC-based regimen in the treatment of 16 extremely severe patients (invasive mechanical ventilation, 15/16; extracorporeal membrane oxygenation, 9/16; and renal replacement therapy, 8/16) infected with DTR GNB. Our case series provides detailed insight into the pharmacokinetic profile and the microbiological data in real-life conditions. In the narrative review, we discuss the interest of FDC in the treatment of non-fermentative GNB in critically ill patients. We reviewed the microbiological spectrum, resistance mechanisms, pharmacokinetics/pharmacodynamics, efficacy and safety profiles, and real-world evidence for FDC. On the basis of our experience and the available literature, we discuss the optimal FDC-based regimen, FDC dosage, and duration of therapy in critically ill patients with DTR non-fermentative GNB infections.
RESUMEN
We studied the macrolide resistance and serotypes of 585 group A streptococcus (GAS) isolates collected from French children with pharyngitis. Nineteen isolates (3.2%) were erythromycin-resistant and harbored the following resistance genes: 31.6% mef(A), 15.8% erm(A), and 52.6% erm(B). The 19 isolates included 7 different emm types (4, 1, 11, 2, 28, 12, and 77) and 7 corresponding multilocus sequence types. The current fall in macrolide consumption has led to a very low rate of GAS macrolide resistance.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Macrólidos/farmacología , Faringitis/epidemiología , Infecciones Estreptocócicas/epidemiología , Streptococcus pyogenes/efectos de los fármacos , Adolescente , Niño , Preescolar , Análisis por Conglomerados , Francia/epidemiología , Genes Bacterianos , Genotipo , Humanos , Tipificación de Secuencias Multilocus , Faringitis/microbiología , Prevalencia , Serotipificación , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/clasificación , Streptococcus pyogenes/aislamiento & purificación , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: The diagnosis of bacterial infections continues to rely on culture, a slow process in which antibiotic susceptibility profiles of potential pathogens are made available to clinicians 48 hours after sampling, at best. Recently, clinical metagenomics, the metagenomic sequencing of samples with the purpose of identifying microorganisms and determining their susceptibility to antimicrobials, has emerged as a potential diagnostic tool that could prove faster than culture. Clinical metagenomics indeed has the potential to detect antibiotic resistance genes (ARGs) and mutations associated with resistance. Nevertheless, many challenges have yet to be overcome in order to make rapid phenotypic inference of antibiotic susceptibility from metagenomic data a reality. OBJECTIVES: The objective of this narrative review is to discuss the challenges underlying the phenotypic inference of antibiotic susceptibility from metagenomic data. SOURCES: We conducted a narrative review using published articles available in the National Center for Biotechnology Information PubMed database. CONTENT: We review the current ARG databases with a specific emphasis on those which now provide associations with phenotypic data. Next, we discuss the bioinformatic tools designed to identify ARGs in metagenomes. We then report on the performance of phenotypic inference from genomic data and the issue predicting the expression of ARGs. Finally, we address the challenge of linking an ARG to this host. IMPLICATIONS: Significant improvements have recently been made in associating ARG and phenotype, and the inference of susceptibility from genomic data has been demonstrated in pathogenic bacteria such as Staphylococci and Enterobacterales. Resistance involving gene expression is more challenging however, and inferring susceptibility from species such as Pseudomonas aeruginosa remains difficult. Future research directions include the consideration of gene expression via RNA sequencing and machine learning.
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Metagenoma , Metagenómica , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana/genética , Genes BacterianosRESUMEN
Bacteria and archaea have developed multiple antiviral mechanisms, and genomic evidence indicates that several of these antiviral systems co-occur in the same strain. Here, we introduce DefenseFinder, a tool that automatically detects known antiviral systems in prokaryotic genomes. We use DefenseFinder to analyse 21000 fully sequenced prokaryotic genomes, and find that antiviral strategies vary drastically between phyla, species and strains. Variations in composition of antiviral systems correlate with genome size, viral threat, and lifestyle traits. DefenseFinder will facilitate large-scale genomic analysis of antiviral defense systems and the study of host-virus interactions in prokaryotes.
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Antivirales , Archaea , Archaea/genética , Bacterias/genética , Genómica , Células ProcariotasRESUMEN
Multidrug-resistant Enterobacterales, including carbapenemase producers, are currently spreading in health care facilities and the community. The Bichat Claude Bernard hospital in Paris faced a prolonged NDM-producing Enterobacterales (NDM-CPE) outbreak. Whole-genome sequencing (WGS) was performed on all isolated NDM-CPE to evaluate its benefits for outbreak surveillance and comprehension. All NDM-CPE isolates collected during the outbreak period (August 2016 to January 2018) were sequenced using the Illumina NextSeq platform. Gene content and core genomes were compared. Genomics results underwent epidemiological analysis which classified NDM-CPE cases as imported (positive sample during the 48 h after admission), hospital acquired, or uncertain. Over the epidemic period, 61 patients were colonized or infected with 81 distinct NDM-CPE isolates. Klebsiella pneumoniae was the most common species (n = 52, 64%), followed by Escherichia coli (13.5%) and other species (22.5%). In all, 43/52 (83%) K. pneumoniae isolates were clonal (≤18 single nucleotide polymorphisms [SNPs] except for three isolates) and belonged to ST307. The IncFIIK [K2:A-/B-] plasmid carrying blaNDM-1 present in all ST307 K. pneumoniae isolates was also detected in 18 other NDM-CPE isolates. Additionally, eight clonal ST144 Klebsiella oxytoca (≤18 SNPs) isolates lacking the epidemic plasmid were observed. The WGS analyses confirmed the acquired and imported cases except for two patients and resolved uncertain cases, which all turned out to be hospital acquisitions. WGS coupled with epidemiological analysis unraveled three epidemic phenomena: mainly the spread of a clonal ST307 K. pneumoniae strain and its conjugative plasmid carrying blaNDM-1 but also the unexpected clonal spread of an ST144 K. oxytoca strain. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) can spread and cause outbreaks in health care facilities, resulting in increased lengths of stay and morbidity. Control of outbreaks requires epidemiological surveillance, usually based on microbiological screening and patient follow-up. These data are sometimes insufficient to identify the routes of dissemination. There is therefore a need for more accurate tools such as whole-genome sequencing (WGS), which allows comparison of isolates but also plasmids carrying resistance with a high definition. In this work, we retrospectively sequenced the genomes of all NDM-producing Enterobacterales isolated during a prolonged NDM outbreak in our hospital. We demonstrated the value of combining WGS with epidemiological data that unveiled the multiple mechanisms of dissemination involved in the outbreak and confirmed transmission cases. This work reinforces the potential of WGS in outbreak surveillance and suggests that it could improve outbreak control if used in real time by confirming transmission cases more rapidly.
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Brotes de Enfermedades , Klebsiella pneumoniae , Escherichia coli/genética , Hospitales , Humanos , Klebsiella pneumoniae/genética , Estudios Retrospectivos , beta-LactamasasRESUMEN
Recent studies have highlighted the importance of ecological interactions in dysbiosis of gut microbiota, but few focused on their role in antibiotic-induced perturbations. We used the data from the CEREMI trial in which 22 healthy volunteers received a 3-day course of ceftriaxone or cefotaxime antibiotics. Fecal samples were analyzed by 16S rRNA gene profiling, and the total bacterial counts were determined in each sample by flux cytometry. As the gut exposure to antibiotics could not be experimentally measured despite a marked impact on the gut microbiota, it was reconstructed using the counts of susceptible Escherichia coli. The dynamics of absolute counts of bacterial families were analyzed using a generalized Lotka-Volterra equations and nonlinear mixed effect modeling. Bacterial interactions were studied using a stepwise approach. Two negative and three positive interactions were identified. Introducing bacterial interactions in the modeling approach better fitted the data, and provided different estimates of antibiotic effects on each bacterial family than a simple model without interaction. The time to return to 95% of the baseline counts was significantly longer in ceftriaxone-treated individuals than in cefotaxime-treated subjects for two bacterial families: Akkermansiaceae (median [range]: 11.3 days [0; 180.0] vs. 4.2 days [0; 25.6], p = 0.027) and Tannerellaceae (13.7 days [6.1; 180.0] vs. 6.2 days [5.4; 17.3], p = 0.003). Taking bacterial interaction as well as individual antibiotic exposure profile into account improves the analysis of antibiotic-induced dysbiosis.
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Microbioma Gastrointestinal , Antibacterianos/efectos adversos , Bacterias/genética , Cefotaxima/efectos adversos , Ceftriaxona/efectos adversos , Disbiosis/inducido químicamente , Disbiosis/tratamiento farmacológico , Microbioma Gastrointestinal/genética , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
Bone and joint infections (BJIs) are complex infections that require precise microbiological documentation to optimize antibiotic therapy. Currently, diagnosis is based on microbiological culture, sometimes complemented by amplification and sequencing of the 16S rDNA gene. Clinical metagenomics (CMg), that is, the sequencing of the entire nucleic acids in a sample, was previously shown to identify bacteria not detected by conventional methods, but its actual contribution to the diagnosis remains to be assessed, especially with regard to 16S rDNA sequencing. In the present study, we tested the performance of CMg in 34 patients (94 samples) with suspected BJIs, as compared to culture and 16S rDNA sequencing. A total of 94 samples from 34 patients with suspicion of BJIs, recruited from two sites, were analyzed by (i) conventional culture, (ii) 16S rDNA sequencing (Sanger method), and (iii) CMg (Illumina Technology). Two negative controls were also sequenced by CMg for contamination assessment. Based on the sequencing results of negative controls, 414 out of 539 (76.7%) bacterial species detected by CMg were considered as contaminants and 125 (23.2%) as truly present. For monomicrobial infections (13 patients), the sensitivity of CMg was 83.3% as compared to culture, and 100% as compared to 16S rDNA. For polymicrobial infections (13 patients), the sensitivity of CMg was 50% compared to culture, and 100% compared to 16S rDNA. For samples negative in culture (8 patients, 21 samples), CMg detected 11 bacteria in 10 samples from 5 different patients. In 5/34 patients, CMg brought a microbiological diagnosis where conventional methods failed, and in 16/34 patients, CMg provided additional information. Finally, 99 antibiotic resistance genes were detected in 24 patients (56 samples). Provided sufficient genome coverage (87.5%), a correct inference of antibiotic susceptibility was achieved in 8/8 bacteria (100%). In conclusion, our study demonstrated that the CMg provides complementary and potentially valuable data to conventional methods of BJIs diagnosis.
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For decades, the term "anti-anaerobic" has been commonly used to refer to antibiotics exhibiting activity against anaerobic bacteria, also designated as anaerobes. This term is used in various situations ranging from infections associated with well-identified pathogens like Clostridioides difficile, or Fusobacterium necrophorum in Lemierre's syndrome, that require specific antibiotic treatments to polymicrobial infections generally resulting from the decreased permeability of anatomical barriers (e.g., intestinal translocation and stercoral peritonitis) or infectious secondary localizations (e.g., brain abscess and infectious pleurisy). In these cases, the causal bacteria generally remain unidentified and the antimicrobial treatment is empirical. However, major progress in the knowledge of human bacterial microbiotas in the last 10 years has shown how diverse are the species involved in these communities. Here, we sought to reappraise the concept of anti-anaerobic spectrum in the light of recent advances in the microbiota field. We first highlight that the term anaerobic itself does not represent the tremendous diversity of the bacteria it spans, and then we stress that the antibiotic susceptibility profiles for most anaerobic bacteria remain unaddressed. Furthermore, we provide examples challenging the relevance of the "anti-anaerobic" spectrum from a clinical and ecological perspective.
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Antibacterianos/farmacología , Bacterias Anaerobias/efectos de los fármacos , Microbiota/efectos de los fármacos , Anaerobiosis , Animales , Humanos , Terminología como AsuntoRESUMEN
Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of microorganisms and their susceptibility to antimicrobials. Over the last decades, sequencing and bioinformatic solutions supporting CMg have much evolved and an increasing number of case reports and series covering various infectious diseases have been published. Metagenomics is a new approach to infectious disease diagnosis that is currently being developed and is certainly one of the most promising for the coming years. However, most CMg studies are retrospective, and few address the potential impact CMg could have on patient management, including initiation, adaptation, or cessation of antimicrobials. In this narrative review, we have discussed the potential role of CMg in bacteriology, virology, mycology, and parasitology. Several reports and case-series confirm that CMg is an innovative tool with which one can (i) identify more microorganisms than with conventional methods in a single test, (ii) obtain results within hours, and (iii) tailor the antimicrobial regimen of patients. However, the cost-efficiency of CMg and its real impact on patient management are still to be determined.