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 13,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The morbidity and mortality of patients with cystic fibrosis (CF) is primarily determined by chronic and debilitating lung infections caused by a surprisingly narrow spectrum of bacterial pathogens. Pseudomonas aeruginosa is by far the most prevalent life-threatening CF pathogen. In the absence of aggressive early therapy, it infects the majority of adult patients and determines long-term survival. The epidemiology of CF pulmonary infections continues to evolve. Amongst the most recent CF pathogens to have emerged are a group of closely related bacteria, known as the Burkholderia cepacia complex. These organisms are a particular challenge due to inherent antibiotic resistance, the potential for patient-to-patient spread, and the risk of 'cepacia syndrome', a rapid fulminating pneumonia sometimes accompanied by bacteremia. Strict cross-infection control was prompted by early epidemiological experience of the B. cepacia complex and is essential in the management of all CF pathogens.
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PMID:Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. 1766 52

Systematic reviews and meta-analyses have put into perspective the clinical implications of in vitro synergy (Box 1). Randomized, controlled trials are the cornerstone of evidence-based medicine. The trials included in the meta-analyses described in this article are the building blocks of evidence. Individual trials, however, were individually underpowered to address the broader clinical question and relevant patient-related outcomes. On the question of combination therapy, meta-analyses have shaped the complete picture. The interactions observed in vitro have not been shown to improve patient-related outcomes. Authors of systematic reviews have the privilege of considering and selecting the clinical outcomes most relevant for the individual patient. Thus, all-cause mortality, rather than treatment failure with antibiotic modifications or infection-related mortality, has been selected for the assessment of patients who had severe gram-negative infections and febrile neutropenia. Mortality and relapse were assessed for patients who had endocarditis, and clinical and lung function scores were assessed for patients who had cystic fibrosis. The authors hope that the dissemination of these reviews will lead clinicians and researchers to consider primarily these outcomes when appraising or designing clinical research. These are the outcomes that clinicians target when treating the patient. Systematic reviews have the virtue of a broad, systematic, and explicit search. In some areas, such as the use of combination therapy to treat gram-positive infections in general, and specifically to treat endocarditis and Pseudomonas aeruginosa bacteremia, the main contribution of the reviews was to show that current practice is based on very limited clinical evidence. This finding does not refute current practice but should serve to guide future trials and opens the possibility for a different choice of therapy when standard guidelines are difficult to implement. The fact that to date no evidence has been accrued for these infections is not surprising. The clinical question of combination therapy is of no major interest to pharmaceutical companies sponsoring most trials; the infections are rare; and the study design is complex. This gap in knowledge calls for a new trial paradigm: collaborative investigator-initiated, multicenter trials. When randomized, controlled trials are unfeasible, the use of novel methods for adjustments in observational studies, such as propensity analyses using large databases, might approximate the true effect of combination therapy in a wider patient population.
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PMID:Combination antimicrobial treatment versus monotherapy: the contribution of meta-analyses. 1939 9

Over 60% of bacterial infections (and up to 80% of chronic infections) are currently considered to involve microbial growth in biofilms. This peculiar form of life poses an array of problems in human clinical practice, from infections associated with the implant of prosthetic devices and dental plaque formation to diseases such as cystic fibrosis, otitis media, and endocarditis. Biofilms are also at the basis of a variety of problems in industry. This report describes the biofilms produced by Streptococcus pneumoniae. This bacterium often colonizes the upper airways in humans as a normal commensal, yet it may spread to other areas of the body, causing otitis media, pneumonia, or invasive diseases such as bacteremia and meningitis. The capacity of S. pneumoniae to form biofilms had not been explored until recently. Several newly developed in vitro systems have allowed to test the capacity of S. pneumoniae to form biofilms, and to analyze the influence of several factors, including DNA and proteins-which play a role in the virulence of this "supergerm" in the formation and development of biofilms. In this brief review, we update the knowledge available on pneumococcal biofilm formation and the unusual features of this structure.
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PMID:Pneumococcal biofilms. 1978 27

Bacteria belonging to the "Burkholderia cepacia complex" (Bcc) often cause fatal pulmonary infections in cystic fibrosis patients, yet little is know about the underlying molecular mechanisms. These Gram-negative bacteria can adopt an intracellular lifestyle, although their ability to replicate intracellularly has been difficult to demonstrate. Here we show that Bcc bacteria survive and multiply in macrophages of zebrafish embryos. Local dissemination by nonlytic release from infected cells was followed by bacteremia and extracellular replication. Burkholderia cenocepacia isolates belonging to the epidemic electrophoretic type 12 (ET12) lineage were highly virulent for the embryos; intravenous injection of <10 bacteria of strain K56-2 killed embryos within 3 days. However, small but significant differences between the clonal ET12 isolates K56-2, J2315, and BC7 were evident. In addition, the innate immune response in young embryos was sufficiently developed to control infection with other less virulent Bcc strains, such as Burkholderia vietnamiensis FC441 and Burkholderia stabilis LMG14294. A K56-2 cepR quorum-sensing regulator mutant was highly attenuated, and its ability to replicate and spread to neighboring cells was greatly reduced. Our data indicate that the zebrafish embryo is an excellent vertebrate model to dissect the molecular basis of intracellular replication and the early innate immune responses in this intricate host-pathogen interaction.
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PMID:Burkholderia cenocepacia creates an intramacrophage replication niche in zebrafish embryos, followed by bacterial dissemination and establishment of systemic infection. 2008 83

Emergence of multidrug-resistant Gram-negative nosocomial pathogens has led to resurgence of colistin use. Safety and efficacy data regarding colistin use in pediatric patients are sparse, while optimal dosage has not been defined. We present a case series of neonates and children without cystic fibrosis treated with various doses of colistin intravenously. The records of patients who received colistin in a tertiary-care hospital from January 2007 to March 2009 were reviewed. Thirteen patients (median age 5 years, range 22 days to 14 years) received 19 courses of colistin as treatment of pneumonia, central nervous system infection, bacteremia, or complicated soft tissue infection. The isolated pathogens were Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Daily dose of colistin (colistimethate) ranged between 40,000 and 225,000 IU/kg. Duration of administration ranged from 1 to 133 days. Other antimicrobials were co-administered in 18/19 courses. Increase of serum creatinine in one patient was associated with co-administration of colistin and gentamicin. Sixteen of 19 courses had a favorable outcome, and only two of the three deaths were infection-related. Colistin intravenous administration appears well tolerated even at higher than previously recommended doses and of prolonged duration.
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PMID:Colistin administration to pediatric and neonatal patients. 2150 29

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and severe chronic lung infections in cystic fibrosis patients. The reference strains PA14 and PAO1 have been studied extensively, revealing that PA14 is more virulent than PAO1 in diverse infection models. Among other factors, this may be due to two pathogenicity islands, PAPI-1 and PAPI-2, both present in PA14 but not in PAO1. We compared the global contributions to virulence of PAPI-1 and PAPI-2, rather than that of individual island-borne genes, using murine models of acute pneumonia and bacteremia. Three isogenic island-minus mutants (PAPI-1-minus, PAPI-2-minus, and PAPI-1-minus, PAPI-2-minus mutants) were compared with the wild-type parent strain PA14 and with PAO1. Our results showed that both islands contributed significantly to the virulence of PA14 in acute pneumonia and bacteremia models. However, in contrast to the results for the bacteremia model, where each island was found to contribute individually, loss of the 108-kb PAPI-1 island alone was insufficient to measurably attenuate the mutant in the acute pneumonia model. Nevertheless, the double mutant was substantially more attenuated, and exhibited a lesser degree of virulence, than even PAO1 in the acute pneumonia model. In particular, its ability to disseminate from the lungs to the bloodstream was markedly inhibited. We conclude that both PAPI-1 and PAPI-2 contribute directly and synergistically in a major way to the virulence of PA14, and we suggest that analysis of island-minus strains may be a more appropriate way than individual gene knockouts to assess the contributions to virulence of large, horizontally acquired segments of DNA.
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PMID:Pathogenicity islands PAPI-1 and PAPI-2 contribute individually and synergistically to the virulence of Pseudomonas aeruginosa strain PA14. 2012 16

We report for the first time 2 cases of multidrug-resistant Burkholderia cenocepacia J2315 isolated from blood samples of patients without cystic fibrosis from a pediatric unit in a hospital in India. The first patient presented with community-acquired bacteremia, and the second patient was immunocompromised and developed hospital-acquired infection approximately 17 days after admission. The isolates from both patients were multidrug-resistant and strong biofilm producers. Surveillance cultures identified the secondary sources of the infections, but not the primary sources.
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PMID:Isolation of Burkholderia cenocepacia J 2315 from non-cystic fibrosis pediatric patients in India. 2153 Dec 70

Data describing the risk of lung transplantation (LT), clinical features, and outcomes of patients with cystic fibrosis (CF) infected with Burkholderia gladioli are limited. Herein, we report a case of disseminated B. gladioli infection characterized by bacteremia, necrotizing pneumonia, lung abscess, and empyema in a lung transplant recipient with CF, highlight the importance of accurate microbiological identification, and review published outcomes of LT in CF patients infected with B. gladioli, which include cases of pneumonia, tracheobronchitis, bacteremia, and abscesses, and demonstrate an all-cause 1-year mortality of approximately 23%, often after combined medical and surgical treatment.
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PMID:Fatal Burkholderia gladioli infection misidentified as Empedobacter brevis in a lung transplant recipient with cystic fibrosis. 2242 3

Burkholderia cepacia complex (BCC) bacteria can cause devastating chronic infections in people with cystic fibrosis. Of particular concern is "cepacia syndrome," a rapidly progressive and usually fatal decline in health, characterized by a necrotizing bacteremic pneumonia. An important component of defense against bloodstream infections is the bactericidal action of serum. Traditional methods to determine the capacity of bacterial isolates to resist the bactericidal effects of serum are relatively low-throughput viability assays. In this study, we developed a novel growth-based assay for serum susceptibility, which allows for high throughput analysis. We applied this assay to a range of clinical isolates of BCC as well as isolates comprising the BCC experimental strain panel. Our data demonstrate that isolates from all species of BCC examined can possess serum resistant or serum sensitive/intermediate phenotypes. Of particular clinical significance, we also found no direct link between the last saved pulmonary isolate from patients who subsequently developed "cepacia syndrome" and their capacity to resist the inhibitory effects of human serum, suggesting serum resistance cannot be used as a marker of an isolate's capacity to escape from the lung and cause bacteremia.
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PMID:Serum susceptibility in clinical isolates of Burkholderia cepacia complex bacteria: development of a growth-based assay for high throughput determination. 2291 58

Lung transplantation has become an excellent treatment option for patients with cystic fibrosis (CF) and bronchiectasis with very advanced lung disease. Despite the challenges that the CF patients present, survival is more favorable than that seen in patients with chronic obstructive pulmonary disease and pulmonary fibrosis. Although those CF and bronchiectasis patients with severe respiratory disease are often infected with organisms that display in vitro resistance to the commonly used antibiotics, they usually have successful outcomes with transplantation, which are reported to be the same as in those patients with less resistant bacteria. Preoperative synergy testing has been demonstrated to reduce the presence of postoperative bacteremia and empyema in patients with CF. Newer challenges include the increasing presence of nontuberculous mycobacteria and in particular the rapid grower Mycobacterium abscessus, for which patient-to-patient spread has been recently recognized. The increased recognition of gastroesophageal reflux offers challenges regarding when and to whom one should offer fundoplication. Most potential CF recipients have metabolic bone disease warranting treatment, especially with the significant loss of bone density seen in the first year after transplantation. Diabetes mellitus, renal dysfunction, and hypertension and their consequences remain common and are of increasing importance as median survival increases in excess of 10 years. With increased experience, more programs are now transplanting patients who require membrane oxygenator support in addition to noninvasive ventilation pretransplantation and the use of a membrane device in the awake patient principally to remove excessive CO2 and reduce acidemia is worthy of note (Novalung; Novalung GmbH, Heilbronn, Federal Republic of Germany). Many centers now take the view that an awake and ambulant patient receiving such support represents a more favorable option than an intubated patient. The limiting factor in lung transplantation remains the number of organs available. Efforts to increase the donor pool, such as low tidal volume ventilation, are effective in allowing a greater percentage of offered organs to be accepted. Perhaps the most encouraging development, however, is that of ex vivo lung perfusion. This permits not only the ability to measure the function of the lungs, something of great value for lungs from donors with circulatory death (donation after cardiac death), but also the potential to introduce lung repair and convert a nonusable lung to one that can be safely used for transplantation.
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PMID:Lung transplantation for cystic fibrosis and bronchiectasis. 2382 5


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