Risk factors for emergence ofStenotrophomonas maltophilia in cystic fibrosis

Talmaciu, Isaac; Varlotta, Laurie; Mortensen, Joel E.; Schidlow, Daniel V.

doi:10.1002/1099-0496(200007)30:1<10::aid-ppul3>3.0.co;2-q

Cited by 81 publications

(65 citation statements)

References 21 publications

(23 reference statements)

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“…maltophilia, like P. aeruginosa, has the potential to contribute to the inflammatory process that compromises respiratory function in CF and in hospital-acquired pneumonias. Since few CF patients have an S. maltophilia infection without a concomitant P. aeruginosa infection (34), it is difficult to sort out the relative contribution of each organism to ongoing lung damage. However, our data suggest that targeting S. maltophilia with antimicrobial therapy and perhaps even anti-inflammatory therapy may decrease overall levels of inflammation that contribute to pathology.…”

Section: Discussionmentioning

confidence: 99%

“…maltophilia has been isolated from 10% of CF patients in the United States (Cystic Fibrosis Foundation registry data) (14) and from up to 25% of CF patients in Europe (12,33). Epidemiological studies have suggested that, unlike Burkholderia cenocepacia complex and Pseudomonas aeruginosa infections, the presence of S. maltophilia in CF patients is not associated with a worse clinical outcome (14,34). However, the contribution of this organism to chronic airway inflammation and its ability to persist within biofilms in vivo have not been well studied.…”

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confidence: 99%

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Immunostimulatory Properties of the Emerging Pathogen Stenotrophomonas maltophilia

et al. 2007

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Stenotrophomonas maltophilia is a multiple-antibiotic-resistant opportunistic pathogen that is being isolated with increasing frequency from patients with health-care-associated infections and especially from patients with cystic fibrosis (CF). While clinicians feel compelled to treat infections involving this organism, its potential for virulence is not well established. We evaluated the immunostimulatory properties and overall virulence of clinical isolates of S. maltophilia using the well-characterized opportunistic pathogen Pseudomonas aeruginosa PAO1 as a control. The properties of CF isolates were examined specifically to see if they have a common phenotype. The immunostimulatory properties of S. maltophilia were studied in vitro by stimulating airway epithelial and macrophage cell lines. A neonatal mouse model of pneumonia was used to determine the rates of pneumonia, bacteremia, and mortality, as well as the inflammatory response elicited by S. maltophilia infection. Respiratory and nonrespiratory S. maltophilia isolates were highly immunostimulatory and elicited significant interleukin-8 expression by airway epithelial cells, as well as tumor necrosis factor alpha (TNF-␣) expression by macrophages. TNF-␣ signaling appears to be important in the pathogenesis of S. maltophilia infection as less than 20% of TNFR1 null mice (compared with 100% of wild-type mice) developed pneumonia and bacteremia following intranasal inoculation. The S. maltophilia isolates were weakly invasive, and low-level bacteremia with no mortality was observed. Despite the lack of invasiveness of S. maltophilia, the immunostimulatory properties of this organism and its induction of TNF-␣ expression specifically indicate that it is likely to contribute significantly to airway inflammation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Immunostimulatory Properties of the Emerging Pathogen Stenotrophomonas maltophilia

et al. 2007

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“…Spicuzza et al (46), in a retrospective evaluation of a cohort of Italian CF patients from 1996 to 2006, found that S. maltophilia was the only truly emerging pathogen, as it had never been isolated until 2004, when an incidence of 7% among all patients was recorded and remained constant through 2006. In non-CF patients (e.g., immunocompromised or intensive care unit patients), exposure to wide-spectrum antimicrobial drugs, long-term antimicrobial therapy, previous pulmonary infections, and chronic respiratory disease contribute to S. maltophilia acquisition and increase the risk for respiratory infection with this microorganism (49,51,52). All of these risk factors are present in the CF population (49).…”

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confidence: 99%

“…Although Karpati et al (30) reported that prolonged infection with S. maltophilia was generally associated with worse lung function in CF patients, most studies reported only a mild effect on lung function (2,14,15,29,46,49).…”

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Role of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis

et al. 2010

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Stenotrophomonas maltophilia is a pathogen that causes infections mainly in immunocompromised patients. Despite increased S. maltophilia isolation from respiratory specimens of patients with cystic fibrosis (CF), the real contribution of the microorganism to CF pathogenesis still needs to be clarified. The aim of the present study was to evaluate the pathogenic role of S. maltophilia in CF patients by using a model of acute respiratory infection in DBA/2 mice following a single exposure to aerosolized bacteria. The pulmonary bacterial load was stable until day 3 and then decreased significantly from day 3 through day 14, when the bacterial load became undetectable in all infected mice. Infection disseminated in most mice, although at a very low level. Severe effects (swollen lungs, large atelectasis, pleural adhesion, and hemorrhages) of lung pathology were observed on days 3, 7, and 14. The clearance of S. maltophilia observed in DBA/2 mouse lungs was clearly associated with an early and intense bronchial and alveolar inflammatory response, which is mediated primarily by neutrophils. Significantly higher levels of interleukin-1␤ (IL-1␤), IL-6, IL-12, gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), GRO␣/KC, MCP-1/JE, MCP-5, macrophage inflammatory protein 1␣ (MIP-1␣), MIP-2, and TARC were observed in infected mice on day 1 with respect to controls. Excessive pulmonary infection and inflammation caused systemic effects, manifested by weight loss, and finally caused a high mortality rate. Taken together, our results show that S. maltophilia is not just a bystander in CF patients but has the potential to contribute to the inflammatory process that compromises respiratory function.

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“…When the laboratories were wrong, the three most common species misidentified as P. aeruginosa were A. xylosoxidans, S. maltophilia, and I. limosus. These three species are regarded as emerging pathogens, although their pathogenic role in CF lung disease is unclear and subject to controversy, especially for patients already chronically infected with P. aeruginosa (3,9,19,31,36,38). Fortunately, none of the misidentified bacteria included recognized gram-negative bacillary CF pathogens from the B. cepacia complex (12).…”

Section: Discussionmentioning

confidence: 99%

Low Rates of Pseudomonas aeruginosa Misidentification in Isolates from Cystic Fibrosis Patients

Kidd

Ramsay

et al. 2009

J Clin Microbiol

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Pseudomonas aeruginosa is an important cause of pulmonary infection in cystic fibrosis (CF). Its correct identification ensures effective patient management and infection control strategies. However, little is known about how often CF sputum isolates are falsely identified as P. aeruginosa. We used P. aeruginosa-specific duplex real-time PCR assays to determine if 2,267 P. aeruginosa sputum isolates from 561 CF patients were correctly identified by 17 Australian clinical microbiology laboratories. Misidentified isolates underwent further phenotypic tests, amplified rRNA gene restriction analysis, and partial 16S rRNA gene sequence analysis. Participating laboratories were surveyed on how they identified P. aeruginosa from CF sputum. Overall, 2,214 (97.7%) isolates from 531 (94.7%) CF patients were correctly identified as P. aeruginosa. Further testing with the API 20NE kit correctly identified only 34 (59%) of the misidentified isolates. Twelve (40%) patients had previously grown the misidentified species in their sputum. Achromobacter xylosoxidans (n ‫؍‬ 21), Stenotrophomonas maltophilia (n ‫؍‬ 15), and Inquilinus limosus (n ‫؍‬ 4) were the species most commonly misidentified as P. aeruginosa. Overall, there were very low rates of P. aeruginosa misidentification among isolates from a broad cross section of Australian CF patients. Additional improvements are possible by undertaking a culture history review, noting colonial morphology, and performing stringent oxidase, DNase, and colistin susceptibility testing for all presumptive P. aeruginosa isolates. Isolates exhibiting atypical phenotypic features should be evaluated further by additional phenotypic or genotypic identification techniques.

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Risk factors for emergence ofStenotrophomonas maltophilia in cystic fibrosis

Cited by 81 publications

References 21 publications

Immunostimulatory Properties of the Emerging Pathogen Stenotrophomonas maltophilia

Immunostimulatory Properties of the Emerging Pathogen Stenotrophomonas maltophilia

Role of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis

Low Rates of Pseudomonas aeruginosa Misidentification in Isolates from Cystic Fibrosis Patients

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