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.
    Full-text · Article · Sep 2015 · PeerJ
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    • "Previous studies have shown that, in addition to a lack of effect on lung function decline [3], detection of S. maltophilia in the respiratory tract of individuals with CF was not associated with increased mortality [4]. However, this study did not distinguish between intermittent and chronic infection; subsequent studies of methicillin-resistant Staphylococcus aureus (MRSA) infection in CF, for example, have shown that persistence of infection is an important determinant of poor clinical outcomes [5] [6]. "
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    ABSTRACT: Background: Chronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF. Methods: This was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV1), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection. Results: A total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV1, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09-2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65-4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant. Conclusions: Baseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression.
    Preview · Article · Jan 2013 · Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society
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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.
    Full-text · Article · Aug 2011 · Peptides
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