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Molecular analysis of Burkholderia cepacia complex isolates from a Portuguese cystic fibrosis center: a 7-year study.

ABSTRACT: This work reports results of a systematic molecular analysis involving 113 Burkholderia cepacia complex isolates obtained from 23 cystic fibrosis (CF) patients under surveillance over a 7-year period at the major Portuguese CF center, the Santa Maria Hospital in Lisbon. The majority of the isolates were serial isolates from persistently infected patients (more than one-half of the population examined). In agreement with previous studies, B. cenocepacia (formerly genomovar III) was the most prevalent species; it was isolated from 52% of the patients infected with B. cepacia complex isolates. Contrasting with previous studies, a very significant percentage of the Portuguese CF subpopulation examined was infected with B. cepacia genomovar I (36%) and B. stabilis (18%). B. multivorans was recovered from two of the infected patients. All four of the species or genomovars were associated with poor clinical outcome, including the cepacia syndrome, and gave rise to chronic and transient infections, with the clinical condition depending on the patient and other still-unidentified factors. The B. cepacia epidemic strain marker region was found exclusively in genomovar III strains, while cblA was detected in genomovars I and III, only. There was no clear relation between the presence of these markers and transmissibility. Altogether, our results indicate that the use of these markers or the genomovar status in identifying patients at higher risk for infection is uncertain.

SUBMITTER: Cunha MV

PROVIDER: S-EPMC193798 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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Molecular analysis of Burkholderia cepacia complex isolates from a Portuguese cystic fibrosis center: a 7-year study.

Cunha Mónica V MV Leitão Jorge H JH Mahenthiralingam Eshwar E Vandamme Peter P Lito Luís L Barreto Celeste C Salgado Maria José MJ Sá-Correia Isabel I

Journal of clinical microbiology 20030901 9

This work reports results of a systematic molecular analysis involving 113 Burkholderia cepacia complex isolates obtained from 23 cystic fibrosis (CF) patients under surveillance over a 7-year period at the major Portuguese CF center, the Santa Maria Hospital in Lisbon. The majority of the isolates were serial isolates from persistently infected patients (more than one-half of the population examined). In agreement with previous studies, B. cenocepacia (formerly genomovar III) was the most preva ...[more]

PMID: 12958234

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Project description:Burkholderia cepacia complex (Bcc) infection, associated with cystic fibrosis (CF) is intrinsically multidrug resistant to antibiotic treatment making eradication from the CF lung virtually impossible. Infection with Bcc leads to a rapid decline in lung function and is often a contraindication for lung transplant, significantly influencing morbidity and mortality associated with CF disease. Standard treatment frequently involves antibiotic combination therapy. However, no formal strategy has been adopted in clinical practice to guide successful eradication. A new class of direct-acting, large molecule polycationic glycopolymers, derivatives of a natural polysaccharide poly-N-acetyl-glucosamine (PAAG), are in development as an alternative to traditional antibiotic strategies. During treatment, PAAG rapidly targets the anionic structural composition of bacterial outer membranes. PAAG was observed to permeabilize bacterial membranes upon contact to facilitate potentiation of antibiotic activity. Three-dimensional checkerboard synergy analyses were used to test the susceptibility of eight Bcc strains (seven CF clinical isolates) to antibiotic combinations with PAAG or ceftazidime. Potentiation of tobramycin and meropenem activity was observed in combination with 8-128 μg/mL PAAG. Treatment with PAAG reduced the minimum inhibitory concentration (MIC) of tobramycin and meropenem below their clinical sensitivity breakpoints (≤4 μg/mL), demonstrating the ability of PAAG to sensitize antibiotic resistant Bcc clinical isolates. Fractional inhibitory concentration (FIC) calculations showed PAAG was able to significantly potentiate antibacterial synergy with these antibiotics toward all Bcc species tested. These preliminary studies suggest PAAG facilitates a broad synergistic activity that may result in more positive therapeutic outcomes and supports further development of safe, polycationic glycopolymers for inhaled combination antibiotic therapy, particularly for CF-associated Bcc infections.

Project description:BackgroundChronic infection with Burkholderia cepacia complex species remains a significant problem for clinicians treating people with cystic fibrosis. Colonisation with Burkholderia cepacia complex species is linked to a more rapid decline in lung function and increases morbidity and mortality. There remain no objective guidelines for strategies to eradicate Burkholderia cepacia complex in cystic fibrosis lung disease, as these are inherently resistant to the majority of antibiotics and there has been very little research in this area. This review aims to examine the current treatment options for people with cystic fibrosis with acute infection with Burkholderia cepacia complex and to identify an evidence-based strategy that is both safe and effective. This is an updated version of the review.ObjectivesTo identify whether treatment of Burkholderia cepacia complex infections can achieve eradication, or if treatment can prevent or delay the onset of chronic infection. To establish whether following eradication, clinical outcomes are improved and if there are any adverse effects.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Last search: 12 March 2019.We also searched electronic clinical trials registers for the USA and Europe.Date of last search: 12 March 2019.Selection criteriaRandomised or quasi-randomised studies in people with cystic fibrosis of antibiotics or alternative therapeutic agents used alone or in combination, using any method of delivery and any treatment duration, to eradicate Burkholderia cepacia complex infections compared to another antibiotic, placebo or no treatment.Data collection and analysisTwo authors independently assessed for inclusion in the review the eligibility of 52 studies (79 references) identified by the search of the Group's Trial Register and the other electronic searches.Main resultsNo studies looking at the eradication of Burkholderia cepacia complex species were identified.Authors' conclusionsThe authors have concluded that there was an extreme lack of evidence in this area of treatment management for people with cystic fibrosis. Without further comprehensive studies, it is difficult to draw conclusions about a safe and effective management strategy for Burkholderia cepacia complex eradication in cystic fibrosis. Thus, while the review could not offer clinicians evidence of an effective eradication protocol for Burkholderia cepacia complex, it has highlighted an urgent need for exploration and research in this area, specifically the need for well-designed multi-centre randomised controlled studies of a variety of (novel) antibiotic agents.

Dataset Information

Molecular analysis of Burkholderia cepacia complex isolates from a Portuguese cystic fibrosis center: a 7-year study.

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Molecular analysis of Burkholderia cepacia complex isolates from a Portuguese cystic fibrosis center: a 7-year study.

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