Association between Stenotrophomonas maltophilia and lung function in Cystic Fibrosis

Department of Pediatrics, University of Washington Seattle, Seattle, Washington, United States
Thorax (Impact Factor: 8.29). 12/2004; 59(11):955-9. DOI: 10.1136/thx.2003.017707
Source: PubMed


Stenotrophomonas maltophilia (SM) is a Gram-negative non-fermenting bacteria cultured from the sputum of patients with cystic fibrosis (CF). To date, no information is available regarding the effect of this organism on lung function in CF.
A cohort study was conducted to assess the effect of SM on lung function among CF patients aged > or =6 years in the CF Foundation National Patient Registry from 1994 to 1999. Repeated measures regression was used to assess the association between SM and lung function.
The cohort consisted of 20 755 patients with median age at entry of 13.8 years and median follow up time of 3.8 years; 2739 patients (13%) were positive at least once for SM and 18 016 (87%) were never positive. After adjusting for sex, height and age, patients with SM had a mean forced expiratory volume in 1 second which was 0.09 l less (95% CI 0.05 to 0.14) than those without SM. The mean rate of decline associated with SM positivity was 0.025 l/year (95% CI 0.012 to 0.037) but, after adjusting for confounders (sex, height, weight, intravenous antibiotic courses, hospital admissions, pancreatic insufficiency, and Pseudomonas aeruginosa and Burkholderia cepacia status), the mean rate of decline decreased to 0.008 l/year (-0.008, 95% CI -0.019 to 0.003).
Although CF patients with SM have worse lung function at the time of positivity, no association was found between SM and increased rate of decline after controlling for confounders.

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    • "The incidence of S. maltophilia in CF patients varies (Goss et al., 2004; Dalbøge et al., 2011) but has been shown to be increasing in some locations (Emerson et al., 2010). Analyses of the impact of S. maltophilia infection are contradictory with some studies reporting little or no effect on lung function (Goss et al., 2004; Dalbøge et al., 2011) while others report poorer clinical status (Talmaciu et al., 2000) and an increased risk of pulmonary exacerbation with chronic infection (Waters et al., 2011). "
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    ABSTRACT: The genetic disorder cystic fibrosis is a life-limiting condition affecting ∼70,000 people worldwide. Targeted, early, treatment of the dominant infecting species, Pseudomonas aeruginosa, has improved patient outcomes; however, there is concern that other species are now stepping in to take its place. In addition, the necessarily long-term antibiotic therapy received by these patients may be providing a suitable environment for the emergence of antibiotic resistance. To investigate these issues, we employed whole-genome sequencing of 28 non-Pseudomonas bacterial strains isolated from three paediatric patients. We did not find any trend of increasing antibiotic resistance (either by mutation or lateral gene transfer) in these isolates in comparison with other examples of the same species. In addition, each isolate contained a virulence gene repertoire that was similar to other examples of the relevant species. These results support the impaired clearance of the CF lung not demanding extensive virulence for survival in this habitat. By analysing serial isolates of the same species we uncovered several examples of strain persistence. The same strain of Staphylococcus aureus persisted for nearly a year, despite administration of antibiotics to which it was shown to be sensitive. This is consistent with previous studies showing antibiotic therapy to be inadequate in cystic fibrosis patients, which may also explain the lack of increasing antibiotic resistance over time. Serial isolates of two naturally multi-drug resistant organisms, Achromobacter xylosoxidans and Stenotrophomonas maltophilia, revealed that while all S. maltophilia strains were unique, A. xylosoxidans persisted for nearly five years, making this a species of particular concern. The data generated by this study will assist in developing an understanding of the non-Pseudomonas species associated with cystic fibrosis.
    PeerJ 09/2015; 3(23):e1223. DOI:10.7717/peerj.1223 · 2.11 Impact Factor
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    • "In this respect, both the overall prevalence and incidence of Stenotrophomonas maltophilia isolations from CF respiratory tract secretions have been recently reported [14] [17] [28] [46] [47]. Although the pathogenic role of S. maltophilia in CF is still uncertain [20] [28] [33] the problematic drugresistance patterns and the pathogenic role of this microorganism in non-CF diseases [16] [46] make the increasing frequency of isolation in CF patients a cause for concern. CF pathogens are well adapted to the CF pulmonary environment , as suggested by their increased ability to form biofilms [15] [34] [39] [43], sessile communities inherently recalcitrant to immune defenses and available antibiotic treatment schemes. "
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    ABSTRACT: Six different cathelicidin-derived peptides were compared to tobramycin for antibacterial and anti-biofilm effects against S. aureus, P. aeruginosa, and S. maltophilia strains isolated from cystic fibrosis patients. Overall, SMAP-29, BMAP-28, and BMAP-27 showed relevant antibacterial activity (MIC(50) 4-8μg/ml), and in some cases higher than tobramycin. In contrast, indolicidin, LL-37, and Bac7(1-35) showed no significant antimicrobial activity (MIC(50)>32μg/ml). Killing kinetics experiments showed that in contrast to tobramycin the active cathelicidin peptides exert a rapid bactericidal activity regardless of the species tested. All three peptides significantly reduced biofilm formation by S. maltophilia and P. aeruginosa strains at 1/2× MIC, although at a lower extent than tobramycin. In addition, BMAP-28, as well as tobramycin, was also active against S. aureus biofilm formation. Preformed biofilms were significantly affected by bactericidal SMAP-29, BMAP-27 and BMAP-28 concentrations, although at a lesser extent than tobramycin. Overall, our results indicate the potential of some cathelicidin-derived peptides for the development of novel therapeutic agents for cystic fibrosis lung disease.
    Peptides 08/2011; 32(9):1807-14. DOI:10.1016/j.peptides.2011.08.002 · 2.62 Impact Factor
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    • "Data regarding the multi-resistant Gram-negative rod S. maltophilia in CF patients are conflicting. Some authors have recorded a decline in lung function in infected patients [8] [9] [10] whereas others found no influence on the lung function [11] [12] [13]. Newer data suggest that patient-to-patient transmission may occur [14] [15], and that patients chronically infected with S. maltophilia is cable of rising a specific antibody response against this bacteria associated with worse lung function [16]. "
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    ABSTRACT: The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear. All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S. maltophilia for at least 2 years without any other chronic Gram-negative infection were matched to two non-infected CF controls. Twenty-one patients were chronically infected with S. maltophilia during the 2-year study period. Fifteen were infected for at least 2 years. The patients in the S. maltophilia group had a steeper decline (-3.2%/year vs. -0.3%/year) in FEV(1) compared to the non-infected CF controls (P=0.03). The rate of decline was the same as observed 3 years before the patients became chronically infected. Chronic infection with S. maltophilia does not lead to a steeper decline in lung function when compared to the period before chronic infection.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 04/2011; 10(5):318-25. DOI:10.1016/j.jcf.2011.03.006 · 3.48 Impact Factor
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