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Infecção e Antibióticos

Horsley A, Jones AM, Lord R.

Cochrane Database Syst Rev. 2016 Jan 20;1:CD009529. doi: 10.1002/14651858.CD009529.pub3.
 

Abstract

BACKGROUND
Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis. Infections dominated by organisms of theBurkholderia cepacia complex, a group of at least 18 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia. Burkholderia cepacia complex bacteria are resistant to many common antibiotics and able to acquire resistance against many more. Following patient segregation in cystic fibrosis medical care, the more virulent epidemic strains are not as frequent, and new infections are more likely to be with less virulent environmentally-acquired strains. Although evidence-based guidelines exist for treating respiratory exacerbations involving Pseudomonas aeruginosa, these cannot be extended toBurkholderia cepacia complex infections. This review, which is an update of a previous review, aims to assess the available trial evidence for the choice and application of treatments for these infections.

OBJECTIVES
To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation and chronically infected with organisms of the Burkholderia cepacia complex.

SEARCH METHODS
We 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.Date of latest search: 28 August 2015.

SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in people with cystic fibrosis chronically infected with organisms of the Burkholderia cepacia complex.

DATA COLLECTION AND ANALYSIS
No relevant trials were identified.

MAIN RESULTS
No trials were included in this review.

AUTHORS’ CONCLUSIONS
Burkholderia cepacia complex infections present a significant challenge for people with cystic fibrosis and their clinicians. The incidence is likely to increase as the cystic fibrosis population ages; and managing and treating these infections will become more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for people with cystic fibrosis who have chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each person individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. Multicentre randomised clinical trials are needed to assess the effectiveness of different antibiotic regimens in people with cystic fibrosisinfected with organisms of the Burkholderia cepacia complex.

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Firmida MC, Pereira RH, Silva EA, Marques EA, Lopes AJ.

Braz J Med Biol Res. 2016;49(4). pii: S0100-879X2016000400703. doi: 10.1590/1414-431X20155097. Epub 2016 Feb 23.

Abstract

The rate of diagnosis of colonization/infection of the airways with Achromobacter xylosoxidans has increased in cystic fibrosis patients, but its clinical significance is still controversial. This retrospective, case-control study aimed to evaluate the clinical impact of A. xylosoxidans colonization/infection in cystic fibrosis patients. Individuals who were chronically colonized/infected (n=10), intermittently colonized/infected (n=15), and never colonized/infected with A. xylosoxidans (n=18) were retrospectively evaluated during two periods that were 2 years apart. Demographic characteristics, clinical data, lung function, and chronic bacterial co-colonization data were evaluated. Of the total study population, 87% were pediatric patients and 65.1% were female. Individuals chronically colonized/infected with A. xylosoxidans had decreased forced expiratory volume in 1 s (51.7% in the chronic colonization/infection group vs 82.7% in the intermittent colonization/infection group vs 76% in the never colonized/infected group). Compared with the other two groups, the rate of co-colonization with methicillin-resistant Staphylococcus aureus was higher in individuals chronically colonized/infected with A. xylosoxidans (P=0.002). Changes in lung function over 2 years in the three groups were not significant, although a trend toward a greater decrease in lung function was observed in the chronically colonized/infected group. Compared with the other two groups, there was a greater number of annual hospitalizations in patients chronically colonized/infected with A. xylosoxidans (P=0.033). In cystic fibrosis patients, there was an increased frequency of A. xylosoxidans colonization/infection in children, and lung function was reduced in patients who were chronically colonized/infected with A. xylosoxidans. Additionally, there were no differences in clinical outcomes during the 2-year period, except for an increased number of hospitalizations in patients with A. xylosoxidans.

PMID: 26909788

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Fusco NM, Toussaint KA, Prescott WA Jr.

Ann Pharmacother. 2015 Apr;49(4):458-68. doi: 10.1177/1060028014567526. Epub 2015 Jan 12.

Abstract

OBJECTIVE
To review the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) in cystic fibrosis (CF).

DATA SOURCES
A search of PubMed, MEDLINE, Cochrane Library and Clinicaltrials.gov databases through November 2014 was conducted using the search terms Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, pulmonary exacerbations, and cystic fibrosis.

STUDY SELECTION AND DATA EXTRACTION
All English-language research articles, case reports, and case series were evaluated. A total of 185 articles were identified related to MRSA and CF; 30 articles that studied treatments of MRSA APE in CF were included.

DATA SYNTHESIS
The persistent presence of MRSA in the respiratory tract of patients with CF has been associated with higher morbidity and an increased risk of death. Limited clinical data exist supporting the efficacy of any specific antimicrobial currently available for the treatment of APE secondary to MRSA.

CONCLUSIONS
Data extrapolated from other populations suggest that vancomycin and linezolid are appropriate first-line treatment options for the treatment of APE secondary to MRSA. Second-line options include doxycycline or minocycline and trimethoprim/sulfamethoxazole, each of which may be useful in patients coinfected with other respiratory pathogens, for which they may provide overlapping coverage. Ceftaroline and ceftobiprole are newer antibiotics that appear to have a potential role in the treatment of APE in CF, but the latter is not currently available to the US market. Although potentially useful, clindamycin is limited by high rates of resistance, telavancin is limited by its toxicity profile, and tigecycline is limited by a lack of demonstrated efficacy for infections that are similar to that seen in the CF population. Studies investigating the clinical utility of the above-cited antibiotics for APE in CF secondary to MRSA are desperately needed to broaden the treatment armamentarium for this medical condition.

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Lo DK, Hurley MN, Muhlebach MS, Smyth AR.

Cochrane Database Syst Rev. 2015 Feb 24;(2):CD009650. doi: 10.1002/14651858.CD009650.pub3.


Abstract

BACKGROUND
Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.Meticillin-resistantStaphylococcus aureus (MRSA) has emerged as, not only an important infection in long-term hospitalised patients, but also as a potentially harmful pathogen in cystic fibrosis, and has been increasing steadily in prevalence internationally. Chronic pulmonary infection with MRSA is thought to confer cystic fibrosis patients with a worse overall clinical outcome and, in particular, result in an increased rate of decline in lung function. Clear guidance for the eradication of MRSA in cystic fibrosis, supported by robust evidence from good quality trials, is urgently needed.

OBJECTIVES
To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication ofMRSA confers better clinical and microbiological outcomes for people with cystic fibrosis.

SEARCH METHODS
Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Cystic Fibrosis Trials Register, PUBMED, MEDLINE, Embase, handsearching article reference lists and through contact with local and international experts in the field.Date of the last search of the Group’s Cystic Fibrosis Trials Register: 04 September 2014.

SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment.

DATA COLLECTION AND ANALYSIS
The authors independently assessed all search results for eligibility. No eligible trials were identified for inclusion.

MAIN RESULTS
No current published eligible trials were identified, although three ongoing clinical trials are likely to be eligible for inclusion in future updates of this review.

AUTHORS’ CONCLUSIONS
We did not identify any randomised trials which would allow us to make any evidence-based recommendations. Although the results of several non-randomised studies would suggest that, once isolated, the eradication of MRSA is possible; whether this has a significant impact on clinical outcome is still unclear. Further research is required to guide clinical decision making in the management of MRSA infection in cystic fibrosis.

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Daines C, VanDeVanter D, Khan U, Emerson J, Heltshe S, McNamara S, Anstead M, Langkamp M, Doring G, Ratjen F, Ramsey B, Gibson RL, Morgan W, Rosenfeld M; EPIC Investigators.

J Cyst Fibros. 2014 Sep;13(5):542-9. doi: 10.1016/j.jcf.2014.06.005. Epub 2014 Jul 11.
 

Abstract

RATIONALE
Pseudomonas aeruginosa (Pa) serology could potentially be a useful adjunct to respiratory culture methods for the detection of initial or early Pa infection in patients with cystic fibrosis (CF).

OBJECTIVE
To evaluate the utility of Pa serology to predict Pa isolation from respiratory (generally oropharyngeal) cultures in the subsequent 6 or 12 months among young children with CF from whom Pa had never been previously cultured. Pa serology was also evaluated in a group of healthy controls.

METHODS
Children ≤ 12 years of age without prior isolation of Pa from respiratory cultures participating in the Early Pseudomonal Infection Control EPIC Observational Study (EPIC OBS) had annual serum samples for measurement of antibodies against alkaline protease, elastase and exotoxin A using a commercial kit; controls had a single serum sample. Logistic regression with generalized estimating equations was used to characterize associations between log10 serum antibody titers and first isolation of Pa from a respiratory culture within the subsequent 6 or 12 months, with adjustment for sex and age. Receiver operating characteristic curves were used to optimize antibody titer cutpoints by age group. The diagnostic properties of each antibody were estimated using these optimized cutpoints.

RESULTS
Pa serology was evaluated in 582 children with CF (2084 serum samples) and 94 healthy controls. There was substantial overlap between serum antibody titers among controls, CF patients who did not acquire Pa (N = 261) and CF patients who did acquire Pa (N = 321). The maximum positive predictive value for first Pa positive culture within the ensuing 6 months was 76.2% and maximum negative predictive value was 72.1% for any antigen or combination of antigens; values were similar for 12 months.

CONCLUSIONS
Pa serology does not appear useful for predicting first Pa positive oropharyngeal culture among young CF patients.

Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Keywords: Cystic fibrosis; Pseudomonas; ROC curves; Serology.

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Mauch RM, Rossi CL, Ribeiro JD, Ribeiro AF, Nolasco da Silva MT, Levy CE.

Diagn Pathol. 2014 Aug 22;9:158. doi: 10.1186/s13000-014-0158-z.

 

Abstract

BACKGROUND
The usefulness of serological tests for detection of P. aeruginosa pulmonary infection in cystic fibrosis (CF) is controversial. Here, we assessed the value of detecting anti-P. aeruginosa IgG by a quantitative enzyme-linked immunosorbent assay (ELISA) for identification of P. aeruginosa infection in patients with cystic fibrosis.

METHODS
Serum concentrations of anti-P. aeruginosa IgG were assessed in 117 CF patients classified according to their P. aeruginosa colonization/infection status (never colonized; free of infection; intermittently colonized and chronically infected) and in 53 healthy subjects by the ELISA test standardized with the St-Ag:1-17 antigen.

RESULTS
The rate of IgG seropositivity and the median of IgG concentrations of this antibody in patients chronically infected were significantly higher than those found in the other CF groups and in the healthy control group.

CONCLUSION
Detection of anti-P. aeruginosa IgG can be an useful tool for identification of P. aeruginosa chronic infection in patients with CF.

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Silva Filho LV, Ferreira Fde A, Reis FJ, Britto MC, Levy CE, Clark O, Ribeiro JD.

J Bras Pneumol. 2013 Jun-Aug;39(4):495-512. doi: 10.1590/S1806-37132013000400015.


Abstract

Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO-an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group.

PMID: 24068273

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Folkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O, Høiby N, Molin S.

Nat Rev Microbiol. 2012 Dec;10(12):841-51. doi: 10.1038/nrmicro2907. Epub 2012 Nov 13.

 

Abstract

The airways of patients with cystic fibrosis (CF) are nearly always infected with many different microorganisms. This environment offers warm, humid and nutrient-rich conditions, but is also stressful owing to frequent antibiotic therapy and the host immune response. Pseudomonasaeruginosa is commonly isolated from the airways of patients with CF, where it most often establishes chronic infections that usually persist for the rest of the lives of the patients. This bacterium is a major cause of mortality and morbidity and has therefore been studied intensely. Here, we discuss how P. aeruginosa evolves from a state of early, recurrent intermittent colonization of the airways of patients with CF to a chronic infection state, and how this process offers opportunities to study bacterial evolution in natural environments. We believe that such studies are valuable not only for our understanding of bacterial evolution but also for the future development of new therapeutic strategies to treat severe chronic infection.

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Vandamme P, Dawyndt P.

Syst Appl Microbiol. 2011 Apr;34(2):87-95. doi: 10.1016/j.syapm.2010.10.002. Epub 2011 Jan 22.
 

Abstract

The Burkholderia cepacia complex is a group of closely related species with conflicting biological properties. Triggered by the devastating effect of pulmonary infections in cystic fibrosis patients, the scientific community generated an unusually large amount of taxonomic data for these bacteria during the past 15 years. This review presents the polyphasic, multilocus and genomic methodology used for the classification and identification of these bacteria. The current state-of-the-art demonstrates that present day taxonomists can replace traditional DNA-DNA hybridizations for species level demarcation and 16S rRNA sequence analysis for studying phylogeny by superior whole genome sequence-based parameters within the framework of polyphasic taxonomic studies.

Copyright © 2010 Elsevier GmbH. All rights reserved.

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