Outbreak of Corynebacterium pseudodiphtheriticum Infection in Cystic Fibrosis Patients, France

Respiratory tract colonization with these bacteria may be common in this population

Genomic analysis of an emerging multiresistant Staphylococcus aureus strain rapidly spreading in cystic fibrosis patients revealed the presence of an antibiotic inducible bacteriophage

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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. REVIEWERS: This article was reviewed by Eric Bapteste, Pierre Pontarotti, and Igor Zhulin. For the full reviews, please go to the Reviewers' comments section

Inquilinus limosus and Cystic Fibrosis

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Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium chimaera </it>is a recently described species within the <it>Mycobacterium avium </it>complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection.</p> <p>Case presentation</p> <p>An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a <it>Mycobacterium avium </it>complex organism further identified as <it>M. chimaera</it>.</p> <p>Conclusion</p> <p>Using sequencing-based methods of identification, we observed that <it>M. chimaera </it>organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with <it>M. avium </it>subsp. <it>hominissuis </it>isolates. We believe that <it>M. chimaera </it>should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.</p

First isolation of two colistin-resistant emerging pathogens, Brevundimonas diminuta and Ochrobactrum anthropi, in a woman with cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis afflicted lungs support the growth of many bacteria rarely implicated in other cases of human infections.</p> <p>Case presentation</p> <p>We report the isolation and identification, by 16S rRNA amplification and sequencing, of two emerging pathogens resistant to colistin, <it>Brevundimonas diminuta </it>and <it>Ochrobactrum anthropi</it>, 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.</p> <p>Conclusion</p> <p>Our results clearly re-emphasize the emergence of new colistin-resistant pathogens in patients with cystic fibrosis.</p

Nocardia farcinica lung infection in a patient with cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. <it>Nocardia </it>are rarely implicated in these infections and few reports of the involvement of this species are found in the literature.</p> <p>Case presentation</p> <p>We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant <it>Nocardia farcinica </it>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.</p> <p>Conclusion</p> <p>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.</p

Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients

Background: 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. Methodology/Principal Findings: 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 (7.263.9 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. Conclusions/Significance: 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 urgentl

Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor

International audienceBackground: As Cystic Fibrosis (CF) treatments drastically improved in recent years, tools to assess their efficiency need to be properly evaluated, especially cross-sectional imaging techniques. High-resolution computed tomography (HRCT) scan response to combined lumacaftor- ivacaftor therapy (Orkambi®) in patients with homozygous for F508del CFTR has not yet been assessed.Methods: We conducted a retrospective observational study in two French reference centers in CF in Marseille hospitals, including teenagers (>12 years old) and adults (>18 years) who had received lumacaftor-ivacaftor and for whom we had at disposal at least two CT scans, one at before therapy and one at least six months after therapy start. CT scoring was performed by using the modified version of the Brody score.Results: 34 patients have been included. The mean age was 26 years (12-56 years). There was a significant decrease in the total CT score (65.5 to 60.3, p = 0.049) and mucous plugging subscore (12.3 to 8.7, p = 0.009). Peribronchial wall thickening (PWT) was significantly improved only in the adult group (29.1 to 27.0, p = 0.04). Improvements in total score, peribronchial thickening, and mucous pluggings were significantly correlated with improvement in FEV1 (forced expiratory volume in 1 s).Conclusions: Treatment with lumacaftor-ivacaftor was associated with a significant improvement in the total CT score, which was mainly related to an improvement in mucous pluggings

Use of high-flow nasal cannula in infants with viral bronchiolitis outside pediatric intensive care units

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