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5.
BMJ Open ; 11(8): e048187, 2021 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-34408046

RESUMEN

INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.


Asunto(s)
COVID-19 , Neumonía , Adulto , Antibacterianos/uso terapéutico , Humanos , Unidades de Cuidados Intensivos , Reacción en Cadena de la Polimerasa Multiplex , Neumonía/tratamiento farmacológico , Polipéptido alfa Relacionado con Calcitonina
6.
Ther Adv Respir Dis ; 15: 17534666211003012, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34098822

RESUMEN

BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors. METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded. RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p = 0.03), the absence of smoking or emphysema (p = 0.05), Staphylococcus aureus (p = 0.001) or Streptococcus spp. (p = 0.05) isolation, and the smaller size of their abscess (p = 0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p = 0.02), particularly when they spontaneously discharged (p = 0.04). Relapses were more frequent in patients with emphysema (p = 0.04) and when Haemophilus influenzae was isolated (p = 0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p = 0.02), and in those who received antibiotics during less than 6 weeks (p = 0.05). CONCLUSION: A duration of antibiotic treatment of less than 6 weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.


Asunto(s)
Absceso Piógeno Hepático , Unidades Hospitalarias , Humanos , Absceso Piógeno Hepático/epidemiología , Absceso Piógeno Hepático/terapia , Estudios Retrospectivos , Factores de Riesgo
8.
BMC Infect Dis ; 19(1): 252, 2019 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-30871501

RESUMEN

BACKGROUND: During fulminant meningococcal septicaemia, meningococci are often observed in the cerebrospinal fluid (CSF) although the patients have frequently no meningeal symptoms. Meningococcal meningitis, by contrast, usually features clinical meningeal signs and biochemical markers of inflammation with elevated white blood cell count (pleiocytosis) in the CSF. Cases of typical symptomatic meningitis without these biochemical features are uncommon in adults. CASE PRESENTATION: A 21-year-old male presented with meningococcal purpura fulminans and disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome requiring hospitalization in the Intensive Care Unit. Despite typical meningeal clinical signs, lumbar puncture showed no pleiocytosis, normal glycorachia and normal proteinorachia, whereas the lactate concentration in the CSF was high (5.8 mmol/L). CSF culture showed a high inoculum of serogroup C meningococci. On day 2, after initial improvement, a recurrence of hypotension led to the diagnosis of acute meningococcal myocarditis, which evolved favourably within a week. During the hospitalization, distal ischemic and necrotic lesions were observed, predominantly on the fingertips, which were treated with local and systemic vasodilators. CONCLUSIONS: We report a rare case of adult meningococcal disease characterized by an intermediate form of meningitis between purulent meningitis and meningeal inoculation from fulminant meningococcal septicaemia, without classical signs of biological inflammation. It highlights the diagnostic value of CSF lactate, which may warrant administration of a meningeal dosing regimen of beta-lactam antibiotics. This case also demonstrates the potential severity of meningococcal myocarditis; we discuss its pathophysiology, which is distinct from other sepsis-related cardiomyopathies. Finally, the observed effects of vasodilators on the meningococcal skin ischemia in this case encourages future studies to assess their efficacy in DIC-associated necrosis.


Asunto(s)
Meningitis Meningocócica/diagnóstico , Miocarditis/diagnóstico , Neisseria meningitidis Serogrupo C/aislamiento & purificación , Púrpura Fulminante/diagnóstico , Adulto , Humanos , Masculino , Meningitis Meningocócica/microbiología , Miocarditis/microbiología , Neisseria meningitidis Serogrupo C/genética , Neisseria meningitidis Serogrupo C/fisiología , Púrpura Fulminante/microbiología , Adulto Joven
10.
Respir Care ; 61(2): 225-34, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26647452

RESUMEN

BACKGROUND: Early recognition and an attempt at obtaining microbiological documentation are recommended in patients with non-community-acquired pneumonia (NCAP), whether hospital-acquired (HAP) or health care-associated (HCAP). We aimed to characterize the clinical features and microbial etiologies of NCAP to assess the impact of microbiological investigation on their management. METHODS: This was a prospective 1-y study in a university hospital with 141 non-mechanically ventilated subjects suspected of having HAP (n = 110) or HCAP (n = 31). RESULTS: Clinical criteria alone poorly identified pneumonia (misdiagnosis in 50% of cases). Microbiological confirmation was achievable in 80 subjects (57%). Among 79 microorganisms isolated, 28 were multidrug-resistant aerobic Gram-negative bacilli and group III Enterobacteriaceae and 6 were methicillin-resistant Staphylococcus aureus. Multidrug-resistant aerobic Gram-negative bacilli accounted for one third of the microorganisms in early-onset HAP and for 50% in late-onset HAP. Methicillin-resistant S. aureus was most often recovered from subjects with HCAP. Inappropriate empirical antibiotics were administered to 36% of subjects with confirmed pneumonia. Forty subjects were admitted to the ICU, 13 (33%) of whom died. Overall, 39 subjects (28%) died in the hospital. CONCLUSIONS: Integrating the microbiological investigation in the complex clinical diagnostic workup of patients suspected of having NCAP is mandatory. Respiratory tract specimens should be obtained whenever possible for appropriate management.


Asunto(s)
Técnicas de Tipificación Bacteriana , Infección Hospitalaria/diagnóstico , Neumonía Bacteriana/diagnóstico , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Errores Diagnósticos , Farmacorresistencia Bacteriana , Enterobacteriaceae/aislamiento & purificación , Femenino , Francia , Bacterias Aerobias Gramnegativas/aislamiento & purificación , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Estudios Prospectivos , Sistema Respiratorio/microbiología
12.
Antimicrob Agents Chemother ; 58(7): 4207-10, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24752259

RESUMEN

We report here the complete nucleotide sequence of two IncR replicons encoding multidrug resistance determinants, including ß-lactam (blaDHA-1, blaSHV-12), aminoglycoside (aphA1, strA, strB), and fluoroquinolone (qnrB4, aac6'-1b-cr) resistance genes. The plasmids have backbones that are similar to each other, including the replication and stability systems, and contain a wide variety of transposable elements carrying known antibiotic resistance genes. This study confirms the increasing clinical importance of IncR replicons as resistance gene carriers.


Asunto(s)
Elementos Transponibles de ADN/genética , Genes MDR/genética , Klebsiella pneumoniae/genética , Factores R/genética , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Secuencia de Bases , Farmacorresistencia Bacteriana Múltiple/genética , Fluoroquinolonas/farmacología , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Resistencia betalactámica/genética , beta-Lactamasas/genética
13.
J Clin Microbiol ; 49(8): 3012-4, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21677064

RESUMEN

Severe infections caused by hypermucoviscous Klebsiella pneumoniae have been reported in Southeast Asian countries over the past several decades. This report shows their emergence in France, with 12 cases observed during a 2-year period in two university hospitals. Two clones (sequence type 86 [ST86] and ST380) of serotype K2 caused five rapidly fatal bacteremia cases, three of which were associated with pneumonia, whereas seven liver abscess cases were caused by K1 strains of ST23.


Asunto(s)
Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/mortalidad , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/epidemiología , Bacteriemia/mortalidad , Bacteriemia/patología , Francia/epidemiología , Hospitales Universitarios , Humanos , Infecciones por Klebsiella/patología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/inmunología , Absceso Hepático/epidemiología , Absceso Hepático/mortalidad , Absceso Hepático/patología , Persona de Mediana Edad , Tipificación Molecular , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/mortalidad , Neumonía Bacteriana/patología , Serotipificación
14.
Microb Drug Resist ; 15(4): 279-86, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19857134

RESUMEN

Eighty-four isolates of Salmonella enterica serovar Livingstone were collected from patients hospitalized in a pediatric ward in Sfax Hospital (South Tunisia). These isolates were responsible for two nosocomial outbreaks in 2000 and 2002. Twenty-eight clinical isolates of S. enterica serovar Livingstone were also obtained in two other Tunisian hospitals in Monastir (Central Tunisia) and Tunis (North Tunisia), respectively, in 2002 and 2003. Pulsed-field gel electrophoresis yielded that these isolates were closely related. Antimicrobial susceptibility testing showed a particular beta-lactam resistance phenotype, suggestive of the presence of an AmpC-type enzyme in 111 of the 112 clinical isolates. bla(ACC-1) was characterized by polymerase chain reaction (PCR) and sequence analysis in the 111 isolates. TEM-1 was characterized in all strains and SHV-2a in only two strains. The genetic organization of bla(ACC-1) was determined by PCR mapping and sequencing. The plasmid-borne bla(ACC-1) gene mapped immediately downstream from ISEcp1. This ISEcp1 insertion sequence was itself disrupted by IS26 insertion sequences. A supplementary deletion of 13 bp was observed in ISEcp1 upstream IS26, in all isolates from Tunis, except one. PCR analysis and sequencing also revealed the presence of tnpR, bla(SCO-1), gdha, IS1353, and TniB Delta 1.


Asunto(s)
Antibacterianos/farmacología , Salmonella enterica/genética , beta-Lactamasas/genética , Secuencia de Bases , Brotes de Enfermedades , Electroforesis en Gel de Campo Pulsado , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Infecciones por Salmonella/epidemiología , Infecciones por Salmonella/microbiología , Salmonella enterica/clasificación , Salmonella enterica/efectos de los fármacos , Salmonella enterica/aislamiento & purificación , Túnez/epidemiología , Resistencia betalactámica/genética
15.
Int J Antimicrob Agents ; 34(4): 340-2, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19570655

RESUMEN

The aim of this study was to investigate the prevalence and diversity of plasmid-mediated AmpC cephalosporinases (PAcBLs) in clinical isolates of Enterobacteriaceae collected between 2003 and 2007 from three Algiers hospitals. Antibiograms were determined on Mueller-Hinton agar plates using the disk diffusion method, and minimum inhibitory concentrations were determined by Etest. Isolates resistant to cefoxitin or ceftazidime were screened for bla(CMY), bla(DHA), bla(FOX) and bla(ACC) as well as extended-spectrum beta-lactamase (ESBL) genes by polymerase chain reaction (PCR). PCR products were sequenced by the Sanger method. Plasmid incompatibility grouping was conducted by PCR-based replicon typing. The prevalence of PAcBLs was 2.18% (11/505), comprising 8 CMY-2 and 3 DHA-1 enzymes. CTX-M-15 was co-produced with CMY-2 in three isolates and with DHA-1 in one isolate; the two remaining DHA-1-producers co-expressed SHV-12 ESBL. This is the first report of plasmid-mediated AmpC from Algeria, with the first detection of DHA-1 in Enterobacter cloacae.


Asunto(s)
Proteínas Bacterianas/genética , Infección Hospitalaria/epidemiología , Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/efectos de los fármacos , Plásmidos/genética , beta-Lactamasas/genética , Argelia/epidemiología , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Cefoxitina/farmacología , Ceftazidima/farmacología , Infección Hospitalaria/microbiología , Enterobacteriaceae/enzimología , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/microbiología , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Prevalencia , Resistencia betalactámica , beta-Lactamasas/metabolismo
16.
J Bacteriol ; 190(15): 5217-23, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18515416

RESUMEN

The plasmid-borne quinolone resistance gene qnrA1 is prevalent in multidrug-resistant Enterobacteriaceae. A chromosomally encoded homologue in Shewanella algae, qnrA3, has been described. We isolated two qnrA3-positive strains, one of Klebsiella pneumoniae (He96) and one of Kluyvera ascorbata (Kas96), from the feces of an immunocompromised outpatient. The qnrA3 allele was identical to that of S. algae except for 5 nucleotides and differed from qnrA1 by 29 nucleotides affecting three amino acids. The analysis of the qnrA3 genetic environment showed that qnrA3 was inserted downstream from an ISCR1 element at a recombination crossover site described for other resistance genes, including qnrA1, and immediately upstream from IS26, a situation not described before. IS26 preceded an incomplete class 1 integron which contained, among other genes, aac(6')-Ib-cr, another transferable quinolone resistance gene, and the beta-lactamase gene bla(OXA-1/30). The 10-kb fragment encompassing qnrA3 was compared to previously described qnrA1-containing plasmids and multidrug-resistant plasmids; it shares identical sequences with pC15a, pHSH2, pQR1, pQKp311H, and pSAL-1 but with rearrangements, deletions, and mutations. Conjugal transfer of qnrA3 was highly efficient (10(-2)) from K. pneumoniae He96 or K. ascorbata Kas96 to Escherichia coli J53 but less so (10(-5)) from either donor to a clinical strain of Enterobacter cloacae. This first description of a plasmid-borne copy and of the in vitro transfer of qnrA3 is taken to illustrate its likely in vivo transfer from S. algae to the Enterobacteriaceae.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Transferencia de Gen Horizontal , Klebsiella pneumoniae/genética , Kluyvera/genética , Plásmidos , Shewanella/genética , Acetiltransferasas/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Secuencia de Bases , Conjugación Genética , Elementos Transponibles de ADN , ADN Bacteriano/química , ADN Bacteriano/genética , Enterobacter cloacae/genética , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/genética , Heces/microbiología , Orden Génico , Humanos , Integrones , Klebsiella pneumoniae/aislamiento & purificación , Kluyvera/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico , beta-Lactamasas/genética
17.
J Clin Microbiol ; 44(11): 4204-7, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16971653

RESUMEN

We report on the first detection of an AmpC-type Ambler class C 1 (ACC-1) beta-lactamase in Citrobacter freundi isolated from a patient also harboring ACC-1-producing Escherichia coli and Klebsiella pneumoniae. We propose a simple cefoxitin-based double-disk synergy test (DDST) for the specific detection of ACC-1 in members of the family Enterobacteriaceae, including natural AmpC producers, in association with a cloxacillin-based DDST as a first-line AmpC-type beta-lactamase screening test.


Asunto(s)
Proteínas Bacterianas/análisis , Citrobacter freundii/enzimología , beta-Lactamasas/análisis , Adolescente , Cefoxitina/farmacología , Citrobacter freundii/efectos de los fármacos , Cloxacilina/farmacología , Conjugación Genética , Heces/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana
19.
Antimicrob Agents Chemother ; 50(2): 607-17, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16436717

RESUMEN

Eleven Klebsiella pneumoniae clinical isolates and one Klebsiella oxytoca clinical isolate showing various pulsed-field gel electrophoresis types and producing an inducible DHA-1 class C beta-lactamase were isolated in the Parisian region between 1998 and 2003. The aim of this study was to compare the genetic organization of the bla(DHA-1) genes in this collection of clinical isolates. In four isolates, the Morganella morganii-derived genomic region containing bla(DHA-1) was inserted in an entire complex sul1-type integron, including a region common to In6-In7 (CR1), as previously described in a bla(DHA-1)-producing Salmonella enterica serovar Enteritidis KF92 isolate from Saudi Arabia in 1992. Different gene cassette arrays were characterized in each of these integrons. In two of them, an additional 10-kb fragment was inserted between the CR1 and the M. morganii-derived region and was similar to the sap (ABC transporter family) and psp (phage shock protein) operons originated from Salmonella enterica serovar Typhimurium. The length of the M. morganii region was variable, suggesting that several independent recombination events have occurred and that open reading frame orf513 encodes a recombinase involved in the mobilization of the resistance genes. The genetic organization of bla(DHA-1) was identical in the eight other isolates. This structure is likely derived from a complex integron following the insertion of IS26, leading to the deletion of the first part of integron. The horizontal transfer of one plasmid carrying that truncated integron was shown for seven of these isolates.


Asunto(s)
Proteínas Bacterianas/genética , Klebsiella/enzimología , Morganella morganii/genética , beta-Lactamasas/genética , Conjugación Genética , Integrones , Klebsiella/efectos de los fármacos , Pruebas de Sensibilidad Microbiana
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