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ABSTRACT: An increasing body of evidence indicates that nondiphtheria corynebacteria may be responsible for respiratory tract infections. We report an outbreak of Corynebacterium pseudodiphtheriticum infection in children with cystic fibrosis (CF). To identify 18 C. pseudodiphtheriticum strains isolated from 13 French children with CF, we used molecular methods (partial rpoB gene sequencing) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Clinical symptoms were exhibited by 10 children (76.9%), including cough, rhinitis, and lung exacerbations. The results of MALDI-TOF identification matched perfectly with those obtained from molecular identification. Retrospective analysis of sputum specimens by using specific real-time PCR showed that approximately 20% of children with CF were colonized with these bacteria, whereas children who did not have CF had negative test results. Our study reemphasizes the conclusion that correctly identifying bacteria at the species level facilitates detection of an outbreak of new or emerging infections in humans.
Emerging Infectious Diseases 08/2010; 16(8):1231-6. · 6.79 Impact Factor
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ABSTRACT: The annual prevalence of Aspergillus colonization (AC) and allergic bronchopulmonary aspergillosis (ABPA) has recently increased in pediatric patients with cystic fibrosis (CF). The reasons remain unclear although a number of factors have been suggested to be involved. This study was set up to investigate the association between potential predisposing factors, including new therapies recommended in CF, and the occurrence of AC or ABPA in children with CF.
The medical records of 85 children monitored regularly in the Pediatric Reference Centre for Cystic Fibrosis Care (RCCFC) of the University Hospital of Marseille (France) were analyzed from the first time they attended the RCCFC until either the occurrence of an end event, or their last visit to the RCCFC. Risk factors for AC or ABPA were analyzed by univariate and multivariate logistic regression.
Eight children developed ABPA and 18 had AC. In univariate analysis, ABPA was significantly associated with RhDNase therapy, sensitization to Alternaria and Candida, and a low body mass index (BMI). Multivariate analysis identified an independent association between low BMI and ABPA (OR = 10.6, 95% CI [2.2-51.8], P = 0.004), and for the first time, between long-term azithromycin therapy and AC (OR = 6.4, 95% CI [2.1-19.5], P = 0.001). This latter association might be explained by the inhibitory effect of azithromycin on both the recruitment and the activation of neutrophils, which represent the first-line defenses against Aspergillus.
The risk factors associated with AC and ABPA in children with CF identified in this comprehensive exploratory study now need to be confirmed in further prospective studies.
Pediatric Pulmonology 08/2010; 45(8):764-71. · 2.53 Impact Factor
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ABSTRACT: Background
The annual prevalence of Aspergillus colonization (AC) and allergic bronchopulmonary aspergillosis (ABPA) has recently increased in pediatric patients with cystic fibrosis (CF). The reasons remain unclear although a number of factors have been suggested to be involved. This study was set up to investigate the association between potential predisposing factors, including new therapies recommended in CF, and the occurrence of AC or ABPA in children with CF.Methods
The medical records of 85 children monitored regularly in the Pediatric Reference Centre for Cystic Fibrosis Care (RCCFC) of the University Hospital of Marseille (France) were analyzed from the first time they attended the RCCFC until either the occurrence of an end event, or their last visit to the RCCFC. Risk factors for AC or ABPA were analyzed by univariate and multivariate logistic regression.ResultsEight children developed ABPA and 18 had AC. In univariate analysis, ABPA was significantly associated with RhDNase therapy, sensitization to Alternaria and Candida, and a low body mass index (BMI). Multivariate analysis identified an independent association between low BMI and ABPA (OR = 10.6, 95% CI [2.2–51.8], P = 0.004), and for the first time, between long-term azithromycin therapy and AC (OR = 6.4, 95% CI [2.1–19.5], P = 0.001). This latter association might be explained by the inhibitory effect of azithromycin on both the recruitment and the activation of neutrophils, which represent the first-line defenses against Aspergillus.Conclusions
The risk factors associated with AC and ABPA in children with CF identified in this comprehensive exploratory study now need to be confirmed in further prospective studies. Pediatr. Pulmonol. 2010; 45:764–771. © 2010 Wiley-Liss, Inc.
Pediatric Pulmonology 07/2010; 45(8):764 - 771. · 2.53 Impact Factor
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ABSTRACT: Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature.
We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon bacterium in patients with cystic fibrosis was proved using a newly developed real-time polymerase chain reaction assay, which indicates that this bacterium, despite treatment, is difficult to eradicate.
Our case report confirms that this organism can be recovered in persons with cystic fibrosis. Its eradication is necessary especially if the patient is to undergo lung transplantation.
Journal of Medical Case Reports 03/2010; 4:84.
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Jean-Marc Rolain,
Patrice François,
David Hernandez,
Fadi Bittar,
Hervé Richet,
Ghislain Fournous,
Yves Mattenberger,
Emmanuelle Bosdure,
Nathalie Stremler,
Jean-Christophe Dubus, Jacques Sarles,
Martine Reynaud-Gaubert,
Stephanie Boniface,
Jacques Schrenzel,
Didier Raoult
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ABSTRACT: Staphylococcus aureus is a major human pathogen responsible for a variety of nosocomial and community-acquired infections. Recent reports show that the prevalence of Methicillin-Resistant S. aureus (MRSA) infections in cystic fibrosis (CF) patients is increasing. In 2006 in Marseille, France, we have detected an atypical MRSA strain with a specific antibiotic susceptibility profile and a unique growth phenotype. Because of the clinical importance of the spread of such strain among CF patients we decided to sequence the genome of one representative isolate (strain CF-Marseille) to compare this to the published genome sequences. We also conducted a retrospective epidemiological analysis on all S. aureus isolated from 2002 to 2007 in CF patients from our institution.
CF-Marseille is multidrug resistant, has a hetero-Glycopeptide-Intermediate resistance S. aureus phenotype, grows on Cepacia agar with intense orange pigmentation and has a thickened cell wall. Phylogenetic analyses using Complete Genome Hybridization and Multi Locus VNTR Assay showed that CF-Marseille was closely related to strain Mu50, representing vancomycin-resistant S. aureus. Analysis of CF-Marseille shows a similar core genome to that of previously sequenced MRSA strains but with a different genomic organization due to the presence of specific mobile genetic elements i.e. a new SCCmec type IV mosaic cassette that has integrated the pUB110 plasmid, and a new phage closely related to phiETA3. Moreover this phage could be seen by electron microscopy when mobilized with several antibiotics commonly used in CF patients including, tobramycin, ciprofloxacin, cotrimoxazole, or imipenem. Phylogenetic analysis of phenotypically similar h-GISA in our study also suggests that CF patients are colonized by polyclonal populations of MRSA that represents an incredible reservoir for lateral gene transfer.
In conclusion, we demonstrated the emergence and spreading of a new isolate of MRSA in CF patients in Marseille, France, that has probably been selected in the airways by antibiotic pressure. Antibiotic-mediated phage induction may result in high-frequency transfer and the unintended consequence of promoting the spread of virulence and/or antibiotic resistance determinants. The emergence of well-adapted MRSA is worrying in such population chronically colonized and receiving many antibiotics and represents a model for emergence of uncontrollable super bugs in a specific niche.
This article was reviewed by Eric Bapteste, Pierre Pontarotti, and Igor Zhulin. For the full reviews, please go to the Reviewers' comments section.
Biology Direct 02/2009; 4:1. · 4.02 Impact Factor
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ABSTRACT: Cystic fibrosis afflicted lungs support the growth of many bacteria rarely implicated in other cases of human infections.
We report the isolation and identification, by 16S rRNA amplification and sequencing, of two emerging pathogens resistant to colistin, Brevundimonas diminuta and Ochrobactrum anthropi, in a 17-year-old woman with cystic fibrosis and pneumonia. The patient eventually responded well to a 2-week regime of imipenem and tobramycin.
Our results clearly re-emphasize the emergence of new colistin-resistant pathogens in patients with cystic fibrosis.
Journal of Medical Case Reports 01/2009; 2:373.
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Fadi Bittar,
Anne Leydier,
Emmanuelle Bosdure,
Alexandre Toro,
Martine Reynaud-Gaubert,
Stéphanie Boniface,
Nathalie Stremler,
Jean-Christophe Dubus, Jacques Sarles,
Didier Raoult,
Jean-Marc Rolain
Emerging Infectious Diseases 07/2008; 14(6):993-5. · 6.79 Impact Factor
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ABSTRACT: There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients.
Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.2+/-3.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus.
Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgently needed to better understand those complex communities in CF pulmonary infections.
PLoS ONE 02/2008; 3(8):e2908. · 4.09 Impact Factor
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ABSTRACT: This randomised cross-over pilot study was undertaken in 10 cystic fibrosis children aged 10 to 63 months to describe lung absorption of tobramycin delivered by the PariLC+/PariTurboboyN (Pari GmbH) and the disposable NL9M/AtomisorBoxPlus (Diffusion Technique Française) nebulising systems.
Each child inhaled 300 mg tobramycin delivered with one or the other apparatus via a facemask in two separate and standardised sessions. Urine was collected for 6 h. Tobramycin concentrations determined by immunoprecipitation were expressed in mg per g of creatinine and compared by a Wilcoxon test for matched pairs. The influences of age, weight and Brasfield score on this parameter were evaluated by correlation tests, and those of sex, previous nebulisation treatment, and crying or coughing were evaluated by Student's t-test.
The amount of tobramycin measured in urines was low and variable. Median values for urinary tobramycin concentration were 47.6 mg/g (14.9-79.6) with the PariLC+ and 42.6 mg/g (6.3-112.8) with the NL9M (p=0.6). PariLC+ delivered tobramycin in 22 min and NL9M in 12 min (p=0.005). Crying or coughing dramatically reduced the amount of tobramycin collected.
This pilot study shows that evaluation of nebulisers based on tobramycin renal excretion is feasible in young children with cystic fibrosis.
Journal of Cystic Fibrosis 05/2007; 6(2):137-43. · 3.19 Impact Factor
