|Year : 2016 | Volume
| Issue : 4 | Page : 110-117
Non-cystic fibrosis bronchiectasis: The long road to multidrug resistant bacteria
José Miguel Sahuquillo-Arce1, Raúl Méndez2, Alicia Hernández-Cabezas1, Rosario Menéndez3
1 Department of Microbiology, IIS/University and Polytechnic Hospital La Fe, Valencia, Spain
2 Department of Pneumology, IIS/University and Polytechnic Hospital La Fe, Valencia, Spain
3 Department of Pneumology, IIS/University and Polytechnic Hospital La Fe, Valencia; CIBER Respiratory Diseases, Valencia, Spain
|Date of Web Publication||17-Jan-2017|
Dr. Rosario Menéndez
Department of Pneumology, University and Polytechnic Hospital La Fe, Avenida Fernando Abril Martorell 106, Valencia 46026
Source of Support: None, Conflict of Interest: None
Bronchiectasis is a common progressive respiratory disease characterized by exacerbations and recurrent chest infections with high morbidity and reduced quality of life. Cole's vicious cycle model explains the evolution of this disease, in which an initial insult in the bronchi, often on a background of impaired mucociliary clearance or bactericidal activity, results in persistence of microbes in the sinobronchial tree and microbial colonization. Microbial overgrowth then causes infection and chronic inflammation, resulting in tissue damage, and impaired mucociliary motility. Subsequent antimicrobial treatments, microbiota interactions, and hypermutation can favor the development of resistance and the appearance of multidrug-resistant (MDR) bacteria. In this paper, we summarize the current knowledge on how bacteria become MDR in noncystic fibrosis bronchiectasis, and which are the most common bacterial pathogens, excluding Mycobacteria.
Keywords: Disease progression, multidrug-resistant bacteria, noncystic fibrosis bronchiectasis
|How to cite this article:|
Sahuquillo-Arce JM, Méndez R, Hernández-Cabezas A, Menéndez R. Non-cystic fibrosis bronchiectasis: The long road to multidrug resistant bacteria. Community Acquir Infect 2016;3:110-7
|How to cite this URL:|
Sahuquillo-Arce JM, Méndez R, Hernández-Cabezas A, Menéndez R. Non-cystic fibrosis bronchiectasis: The long road to multidrug resistant bacteria. Community Acquir Infect [serial online] 2016 [cited 2022 Jan 25];3:110-7. Available from: http://www.caijournal.com/text.asp?2016/3/4/110/198491
| Introduction|| |
Bronchiectasis is a suppurative lung disease which is defined by a permanent and abnormal dilatation of the bronchi and is usually diagnosed on axial images of high-resolution computed tomography scans of the chest. It can be considered the result of a variety of different factors, although most cases are idiopathic. Bronchiectasis is a common progressive respiratory disease characterized by exacerbations and recurrent chest infections with high morbidity and reduced quality of life. Cole's vicious cycle model explains the evolution of this disease, in which an initial insult in the bronchi, often on a background of impaired mucociliary clearance or bactericidal activity, results in persistence of microbes in the sinobronchial tree, and microbial colonization. Microbial overgrowth then causes infection and chronic inflammation, resulting in tissue damage, and impaired mucociliary motility. This then leads to more infection with a cycle of progressive inflammation causing lung damage.,,
Subsequent antimicrobial treatments can favor the development of resistance and the appearance of multidrug-resistant (MDR) bacteria. Unlike in the case of cystic fibrosis, there is scarce information about MDR in noncystic fibrosis bronchiectasis (NCFB), but evidence from recent studies shows that these bacteria have a considerable impact on exacerbations and community-acquired pneumonia.
In this review, we will talk about bacteria involved in these processes and how they can become MDR, excluding Mycobacteria.
| Microbiology of Noncystic Fibrosis Bronchiectasis|| |
Until recently, the lower respiratory tract (LRT) was considered a sterile area that could be colonized briefly by microorganisms from the oropharynx or chronically in lungs with some underlying condition.,, This concept has been modified following the development of new-generation molecular biology techniques, particularly the massive sequencing of regions of 16S ribosomal RNA, which made it possible to detect and identify microorganisms that normally do not grow on routine culture media.
Each person has a unique microbiota, with differences in species and proportions that is acquired at the time of delivery or even before birth, through the placenta., Certain species are found in most healthy individuals at a higher rate and are called core microorganisms; the rest are known as satellite microorganisms.
Segal et al. demonstrated that the microbiota of the LRT differs from the higher respiratory tract in composition and number. Supraglottic core microbiota included larger numbers of Gram-negative anaerobes as (Veillonella and Prevotella), while the pulmonary core microbiota had Gram-positive bacteria (Propionibacterium and Staphylococcus). In addition, the flora of the oropharynx was fifty times more abundant than that of the LRT. However, there is continuity between the microbiota of both anatomical sites that would be part of an interactive gastrointestinal respiratory axis.,
The study of the microbiota in chronic diseases such as NCFB has become a crucial issue and is changing the perspective of pathogenesis. In fact, numerous articles find associations between alterations in the microbiota and illness.,,
The role of the microbiota as an inducer or maintainer of chronic respiratory diseases is gaining in importance. Moreover, damage to the lung tissue may begin years before its effects are detected. Lal et al. observed in two cohorts of newborns that the differences in the microbiota at birth was the common factor to developed bronchopulmonary dysplasia, regardless of birth weight, prematurity, and maternal antimicrobial intake, with a decrease in Firmicutes, especially Lactobacillus, and an increase in Proteobacteria, especially Enterobacteriaceae. The scant effect of prior antibiotic consumption endorses other studies showing that the composition of the microbiota is stable and difficult to alter using antimicrobial treatments, although both the structure of the microbial community and the amount of each species are affected, especially anaerobes., In any case, NCFB patients have complex polymicrobial microbiota with population densities similar to patients with cystic fibrosis.
In NCFB patients, Haemophilus spp., Pseudomonas spp., and Streptococcus spp. are the dominant microorganisms of the core microbiota although proportions vary between stable and exacerbation periods. While some studies link exacerbations with increased density of anaerobes, such as Veillonella, others find associations with multiple genres and decreased diversity. Adaptive changes of the main pathogens in the core microbiota may also trigger exacerbations.,,
Furthermore, the microbiota modulates the inflammatory response. A "healthy" microbiota is associated with a balance between inflammation (Th17) and regulation (ThReg) while an abnormal microbiota is associated with an inflammatory state sustained by the direct action of the microorganisms themselves or the metabolites produced.
Thus, the NCFB microbiota is altered and can determine disease progression. Haemophilus influenzae and Pseudomonas aeruginosa play an important role as core microbiota in NCFB. Both are found in patients with more exacerbations and worse evolution, and both influence the diversity of the accompanying microbiota. Interestingly, when one of them prevails, the other is absent or present in very small numbers.,,
| Nonspecialized Antimicrobial Resistance: Biofilms and Escape Mechanisms|| |
Microorganisms exhibit various strategies to survive in hostile environments. Two of these strategies are the production of biofilms and small colony variants (SCVs), both involved in chronicity of infections and antimicrobial treatment failure.
Microorganisms in nature live mainly in biofilms and only a small percentage live as planktonic bacteria. Within a biofilm, there are multiple environments and even specialized cells; some authors therefore consider this type of organization a multicellular organism.,
Furthermore, expression of virulence factors, membrane proteins, nutrient acquisition, metabolic pathways, and antimicrobial resistance is very different from planktonic cells. This is achieved through cooperation and coordination among community members, through chemical signals known as quorum sensing. This arrangement allows microorganisms to have a greater amount of genetic, phenotypic, and metabolic resources.
Clinically, it is important to note that biofilms are a therapeutic challenge because such structures are resistant to elimination: Phagocytosis is inhibited by matrix components, and antimicrobials cannot act for being inactivated, presenting a poor diffusion or not finding metabolically active cells on which to act.,,
In addition, some pathogenic species such as Candida spp., S. aureus, and P. aeruginosa form biofilms more rapidly in the presence of polymorphonuclear leukocytes and take advantage of neutrophil extracellular traps (NETs) to build biofilms.,
The ultimate goal of biofilms is survival; therefore, a strong immune response would be against the interests of its members. Intriguingly, the interaction between species can reduce the expression of virulence factors, such as Candida spp. on P. aeruginosa, or modulate the inflammatory response, thereby altering both local inflammation and phagocytosis.,,
SCV appear spontaneously but are selected in response to stress, whether environmental, immune, or antimicrobial. SCV microorganisms present a slower rate of growth, express fewer virulence factors, respond worse to quorum sensing molecules, produce fewer antigenic molecules, and interestingly, invade host cells more effectively and survive in intracellular environments, even escaping from phagosomes., These variants are responsible for recolonization by pathogenic microorganisms after antimicrobial treatments, usually because they are too short or ineffective to remove them.
| Bacterial Pathogens in Noncystic Fibrosis Bronchiectasis|| |
According to the current data, NCFB microbiota associated with a worse evolution is mainly dominated by two microorganisms: P. aeruginosa and H. influenzae. Nevertheless, recent investigations have provided a broader view and shown that other microorganisms are involved in NCFB progression, exacerbation, and prognosis, especially MDR.,
The risk of MDR in NCFB seems different depending on the origin of the microorganism. Thus, those adapted to the respiratory tract such as S. pneumoniae and H. influenzae are rarely MDR and are easier to eradicate. In contrast, those that come from different environments, such as Enterobacteriaceae, Gram-negative nonfermenters, and S. aureus, develop resistance and are associated with worse clinical conditions, exacerbations, and community-acquired pneumonia., A 1-year study conducted on sputa from NCFB patients at hospital La Fe, Valencia, Spain, detected 23.2%, 5.4%, and 7.7% of MDR among S. aureus, P. aeruginosa, and S. pneumoniae, respectively; Achromobacter xylosoxidans and Stenotrophomonas maltophilia were also isolated, and all were considered MDR (personal communication).
P. aeruginosa is an opportunistic pathogen often associated with colonization and infection, higher number of hospital admissions, older patients, worse lung function, increased mortality, and a preference for infecting the upper lung lobes.,,
Its virulence factors facilitate survival in the lung, where its presence triggers a global response for its elimination. Virulence factors are in the bacterial membrane (pili, flagella, and lipopolysaccharide), inoculated directly into human cells using type III and IV secretion systems, or excreted to defend itself or get nutrients (alginate, exotoxin A, phospholipase, exoproteases, rhamnolipids, etc.). Exoproteases include elastase, a zinc-dependent metalloenzyme capable of breaking down different proteins found in the extracellular matrix, cytokines and chemokines, and pulmonary surfactant. All these allow P. aeruginosa to survive in a harsh environment, avoid phagocytosis, and cause more invasive infections.,,,
Moreover, this microorganism responds to human endocrine signals. In particular, it was noted that noradrenaline activates the expression of virulence factors, and transforms P. aeruginosa into an invasive phenotype. Hypothetically, it could link stress to NCFB exacerbations.
Of note, P. aeruginosa isolates from patients with an NCFB presented a different phenotype from cystic fibrosis or wild strains, exhibiting an inhibition of virulence factors.
This microorganism presents intrinsic resistance to many antibiotics, mainly by modifying enzymes, impermeability, or efflux pumps. Mutations, loss of porins (OprD), or acquisition of plasmids with resistance determinants such as metallo-β-lactamases, make this microorganism a real threat, leaving very few active drugs against it. Despite this and the high rates of colonization of this microorganism, the emergence of MDR is lower than expected and a high percentage of patients achieve eradication. However, it has been observed that patients with NCFB have a high prevalence of hypermutable strains that leads to the development of resistance mechanisms and justifies age and antimicrobial treatments as selective factors for MDR., It would be advisable to investigate whether more virulent MDR clones with a worse prognosis are circulating among NCFB patients as described in patients with cystic fibrosis.
H. influenzae is related to infections and colonization in younger patients with better lung function and a preference for infecting the lower lung lobes.,,
H. influenzae has different mechanisms that allow it to survive in the lung such as the secretion of IgA proteases, adhesion proteins to lung epithelium (HIF, Hmw1/2, Hap, Hia/Hsf, OMP-2.5, OAPA, PCP, proteins E, and F), molecules that allow it to survive phagocytosis and produce invasive infections (msfA1-14), stress response systems that improve survival in biofilms (DPS), and the production of outer membrane vesicles that act as decoys for the immune response.,,,,,
Unlike P. aeruginosa, this opportunist commensal of the normal flora seems designed to thrive in the airway causing minimal damage. Patients with the prevalence of H. influenzae have fewer and milder exacerbations than patients with P. aeruginosa and require less hospitalization. Surprisingly, patients with the prevalence of H. influenzae have higher levels of tissue metalloproteinase (MMP-2, MMP-12, and MMP-8 activity), which degrades the extracellular matrix and causes local damage, than patients with the prevalence of P. aeruginosa. Nevertheless, both groups of patients presented higher proteolytic activity than NCFB patients with other bacteria and healthy individuals., The induced proteolytic activity may be related to the alleged involvement of H. influenzae in the development of NCFB. Alternatively, the proteolytic activity of bacterial origin may be important in NCFB with the prevalence of P. aeruginosa.
H. influenzae has intrinsic resistance to macrolides, lincosamides, streptogramin B, and ketolides associated with an acrAB-like efflux pump; although macrolides may be clinically effective, especially azithromycin. The prophylactic use of macrolides facilitates the acquisition of erm and mef genes (encoding ribosomal RNA methylases and efflux pumps, respectively) or promotes mutations that cause high-level resistance to these antimicrobials., H. influenzae can also acquire conjugative plasmids with antibiotic resistance genes, such as TEM or ROB β-lactamases, or develop mutations as those described in GyrA and ParC, or PBP3, which makes it resistant to quinolones and β-lactams, respectively.,
Hypermutable strains have been described in patients with cystic fibrosis although no studies have been carried out in patients with NCFB.
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) is a common and important pathogen involved in nosocomial and health-care-related infections. Pneumonia by this microorganism is clinically important because of its severity, the high incidence of complications and the increased mortality that is usually associated with inadequate initial antibiotic therapy.
MRSA has also emerged as an increasingly important cause of community-acquired bacterial infection, and these strains frequently carry Panton-Valentine leukocidin genes.
S. aureus has a number of mechanisms to evade the immune response. These include a capsule, surface proteins, exotoxins, and Panton-Valentine leukocidin. The capsule inhibits phagocytosis and promotes adherence to surfaces. Protein A, collagen adhesin, and staphylococcal clumping factor inhibit opsonization and complement activation. S. aureus also produces a wide array of extracellular toxins such DNAse, which breaks down NETs, or Panton-Valentine leukocidin, which specifically targets leukocytes and produces pores in their membrane, resulting in cell death.
Resistance is acquired by horizontal transfer or chromosomal mutation. Methicillin resistance is carried by the chromosome cassette mecA, which is integrated into orfX, a S. aureus gene of unknown function. This cassette codes a mutant PBP (PBP2a), which has low affinity for β-lactams and makes these bacteria resistant to almost all agents in this group. Interestingly, bacteria with this gene produce better biofilms but are less virulent, a possible explanation for its survival in chronic lung diseases.
This microorganism can asymptomatically colonize people and be part of the normal flora. Its interactions with the host and neighbor microbiota are complex; for example, S. aureus downregulates inflammation induced by P. aeruginosa by decreasing interleukin-8. Nevertheless, it has been related to exacerbations and community-acquired pneumonia in NCFB.,
S. pneumoniae is the leading cause of community-acquired pneumonia worldwide and may be considered an airway specialist pathogen, but it is also associated with exacerbations in NCFB. Beyond its well-known virulence factors, such as pneumolysin, new pathogenic mechanisms are being discovered, including the upregulation of virulence factors in coinfections with respiratory syncytial virus.
MDR are rare and one of the principal means of acquiring resistance factors are biofilm-associated hyperrecombinant strains., Exposure to antimicrobials and poor compliance are decisive in the development and selection of resistance.,,
Enterobacteriaceae are important members of the gut microbiota that can be the cause of infections, most frequently by species of Escherichia More Details, Klebsiella, Enterobacter, Proteus, Providencia, and Serratia. Outside their natural environment, they can behave differently and present more antimicrobial resistance mechanisms; for example, Escherichia coli isolated from respiratory samples tend to be more resistant. MDR Enterobacteriaceae due to extended-spectrum β-lactamases or AmpC enzymes, and those producing carbapenemases have spread throughout the world in recent decades. Many of these isolates are also resistant to other agents, such as fluoroquinolones or aminoglycosides. The very limited therapeutic options available for these organisms are a real challenge and although, once associated with nosocomial infections, they are now found in the community.
An in-depth study of Enterobacteriaceae is beyond the scope of this review, but these microorganisms are relevant in chronic obstructive pulmonary disease and NCFB exacerbations and are community-acquired.,
Gram-negative nonfermenters such as S. maltophilia and A. xylosoxidans are usually associated with cystic fibrosis. However, these microorganisms have been isolated in NCFB and pose a serious challenge due to their intrinsic resistance profiles, which makes them MDR pathogens.,
Effects of antimicrobial treatment on multidrug resistance
Long-lasting antimicrobial treatment during the stable phase of NCFB aims to prevent acute exacerbations and slow the progression of the disease; but presents an important drawback: antimicrobial resistance can arise. Until recently, few studies focused specifically on NCFB; therefore, treatments were extrapolated from studies on cystic fibrosis - some with clinically untoward results.,,,
Recently, clinical trials suggest that the use of antibiotics for extended periods may decrease the symptoms, number of exacerbations, and slow reduction in forced expiratory volume in 1 s. Although results are disparate between studies, the development of resistance was a possible outcome in some trials; however, a Cochrane systematic review on this subject by Welsh et al. found no clear evidence to support this, mainly because of the heterogeneity of populations and the lack of stratification by microbiota composition and antimicrobials used.,,,,,
Importantly, the analysis of these studies did not discriminated patients based on the dominant microorganism in their microbiota. P. aeruginosa is usually susceptible to most antimicrobials studied-aminoglycosides, fluoroquinolones, or colistin-, but it is not to macrolides, which were tested in many of these studies and obtained good results. This may be due to the effect of this group of antibiotics on other members of the microbiota, the inhibitory effect on alginate production and quorum sensing molecules, or its intrinsic immunomodulatory effects.
With regard to exacerbations and community-acquired pneumonia, identifying risk factors to predict the presence of MDR organisms is critical for initiating adequate antimicrobial therapies. Several studies have identified various risk factors in patients with community-acquired pneumonia that may be extrapolated to NCFB. Among these, age, prior antimicrobial treatments, recent hospitalization and institutionalization, colonization by MDR microorganisms, and chronic diseases are crucial.,,,
| Conclusion|| |
Although few studies have evaluated the risk factors related to the emergence of MDR microorganisms in NCFB, we can reconstruct the evolutionary history from what we already know [Figure 1].
An alteration in the lower airway favors changes in the normal microbiota and the emergence of potentially pathogenic microorganisms. These would thrive to quantitatively displace other local microorganisms and become the main component of the microbiota. From here, a cycle of tissue destruction, infection, immune response, and inflammation would be established. This would induce the appearance of hypermutant microorganisms, SCV forms, and pathogenic biofilm generation (mucoid forms).
Added to this, vicious cycle is the selective factor of antimicrobials once clinical signs and symptoms appear. Microorganisms with increased tolerance or those that reside in areas where drugs fail to reach would be selected and after treatment ended, recolonize the lower airway and eventually, produce new exacerbations. Moreover, the elimination of the initial microbiota would allow the acquisition of nosocomial microorganisms. The end result would be a damaged lung colonized by MDR.
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Conflicts of interest
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| References|| |
McShane PJ, Naureckas ET, Tino G, Strek ME. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2013;188:647-56.
Gaga M, Bentley AM, Humbert M, Barkans J, O′Brien F, Wathen CG, et al.
Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis. Thorax 1998;53:685-91.
King P, Bennett-Wood V, Hutchinson P, Robins-Browne R, Holmes P, Freezer N, et al.
Bactericidal activity of neutrophils with reduced oxidative burst from adults with bronchiectasis. APMIS 2009;117:133-9.
Alcaraz V, Polverino E, Rosales E, Giron RM, Mendendez R, Vendrell M, et al
. Exacerbations and pneumonia in bronchiectasis: Clinical and microbiological characterization. Eur Respir J 2015;46:PA367.
Einarsson GG, Comer DM, McIlreavey L, Parkhill J, Ennis M, Tunney MM, et al.
Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers. Thorax 2016;71:795-803.
Martin C, Burgel PR, Lepage P, Andréjak C, de Blic J, Bourdin A, et al.
Host-microbe interactions in distal airways: Relevance to chronic airway diseases. Eur Respir Rev 2015;24:78-91.
Marsh RL, Kaestli M, Chang AB, Binks MJ, Pope CE, Hoffman LR, et al
. The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx. Microbiome 2016;4:37.
Lal CV, Travers C, Aghai ZH, Eipers P, Jilling T, Halloran B, et al
. The airway microbiome at birth. Sci Rep 2016;6:31023.
Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med 2014;6:237ra65.
Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, et al.
Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome 2013;1:19.
Bassis CM, Erb-Downward JR, Dickson RP, Freeman CM, Schmidt TM, Young VB, et al.
Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio 2015;6:e00037.
Rogers GB, van der Gast CJ, Cuthbertson L, Thomson SK, Bruce KD, Martin ML, et al.
Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition. Thorax 2013;68:731-7.
Taylor SL, Wesselingh S, Rogers GB. Host-microbiome interactions in acute and chronic respiratory infections. Cell Microbiol 2016;18:652-62.
Tunney MM, Einarsson GG, Wei L, Drain M, Klem ER, Cardwell C, et al.
Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am J Respir Crit Care Med 2013;187:1118-26.
Purcell P, Jary H, Perry A, Perry JD, Stewart CJ, Nelson A, et al.
Polymicrobial airway bacterial communities in adult bronchiectasis patients. BMC Microbiol 2014;14:130.
Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, et al
. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th phenotype. Nat Microbiol 2016;1:16031.
Rogers GB, Zain NM, Bruce KD, Burr LD, Chen AC, Rivett DW, et al.
A novel microbiota stratification system predicts future exacerbations in bronchiectasis. Ann Am Thorac Soc 2014;11:496-503.
Rogers GB, van der Gast CJ, Serisier DJ. Predominant pathogen competition and core microbiota divergence in chronic airway infection. ISME J 2015;9:217-25.
Pragman AA, Berger JP, Williams BJ. Understanding persistent bacterial lung infections: Clinical implications informed by the biology of the microbiota and biofilms. Clin Pulm Med 2016;23:57-66.
Sahuquillo-Arce JM, Yarad-Auad F, Hernández-Cabezas A. Biofilms: A biological antimicrobial resistance system. In: Méndez-Vilas A, editor. Microbial Pathogens and Strategies for Combating Them: Science, Technology and Education. Badajoz, Spain: Formatex; 2013.
Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol 2009;11:1034-43.
Leid JG, Willson CJ, Shirtliff ME, Hassett DJ, Parsek MR, Jeffers AK. The exopolysaccharide alginate protects Pseudomonas aeruginosa
biofilm bacteria from IFN-gamma-mediated macrophage killing. J Immunol 2005;175:7512-8.
Chandra J, McCormick TS, Imamura Y, Mukherjee PK, Ghannoum MA. Interaction of Candida albicans
with adherent human peripheral blood mononuclear cells increases C. albicans
biofilm formation and results in differential expression of pro- and anti-inflammatory cytokines. Infect Immun 2007;75:2612-20.
Leid JG, Shirtliff ME, Costerton JW, Stoodley P. Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus
biofilms. Infect Immun 2002;70:6339-45.
Ader F, Jawhara S, Nseir S, Kipnis E, Faure K, Vuotto F, et al.
Short term Candida albicans
colonization reduces Pseudomonas aeruginosa
-related lung injury and bacterial burden in a murine model. Crit Care 2011;15:R150.
Johns BE, Purdy KJ, Tucker NP, Maddocks SE. Phenotypic and genotypic characteristics of small colony variants and their role in chronic infection. Microbiol Insights 2015;8:15-23.
Kahl BC, Becker K, Löffler B. Clinical significance and pathogenesis of staphylococcal small colony variants in persistent infections. Clin Microbiol Rev 2016;29:401-27.
Menéndez R, Polverino E, Méndez R, Rosales-Mayor E, Amara-Elori I, Posadas T, et al
. Risk Factors for Bronchiectasis Exacerbations Caused by Multidrug-Resistant Microorganisms. 1 st
World Bronchiectasis Conference Abstract Book; 2016. Available from: http://www.world-bronchiectasis-conference.com
. [Last accessed on 2016 Nov 25].
McDonnell MJ, Jary HR, Perry A, MacFarlane JG, Hester KL, Small T, et al.
Non cystic fibrosis bronchiectasis: A longitudinal retrospective observational cohort study of Pseudomonas
persistence and resistance. Respir Med 2015;109:716-26.
Izhakian S, Wasser WG, Fuks L, Vainshelboim B, Fox BD, Fruchter O, et al
. Lobar distribution in non-cystic fibrosis bronchiectasis predicts bacteriologic pathogen treatment. Eur J Clin Microbiol Infect Dis 2016;35:791-6.
Alhede M, Bjarnsholt T, Givskov M, Alhede M. Pseudomonas aeruginosa
biofilms: Mechanisms of immune evasion. Adv Appl Microbiol 2014;86:1-40.
Kuang Z, Hao Y, Walling BE, Jeffries JL, Ohman DE, Lau GW. Pseudomonas aeruginosa
elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A. PLoS One 2011;6:e27091.
Azghani AO. Pseudomonas aeruginosa
and epithelial permeability: Role of virulence factors elastase and exotoxin A. Am J Respir Cell Mol Biol 1996;15:132-40.
Leidal KG, Munson KL, Johnson MC, Denning GM. Metalloproteases from Pseudomonas aeruginosa
degrade human RANTES, MCP-1, and ENA-78. J Interferon Cytokine Res 2003;23:307-18.
Hegde M, Wood TK, Jayaraman A. The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa
PA14 virulence through the las quorum-sensing pathway. Appl Microbiol Biotechnol 2009;84:763-76.
Varga JJ, Barbier M, Mulet X, Bielecki P, Bartell JA, Owings JP, et al
. Genotypic and phenotypic analyses of a Pseudomonas aeruginosa
chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains. BMC Genomics 2015;16:883.
Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa
: Our worst nightmare? Clin Infect Dis 2002;34:634-40.
Maciá MD, Blanquer D, Togores B, Sauleda J, Pérez JL, Oliver A. Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa
strains causing chronic lung infections. Antimicrob Agents Chemother 2005;49:3382-6.
Aaron SD, Vandemheen KL, Ramotar K, Giesbrecht-Lewis T, Tullis E, Freitag A, et al.
Infection with transmissible strains of Pseudomonas aeruginosa
and clinical outcomes in adults with cystic fibrosis. JAMA 2010;304:2145-53.
Mistry DV, Stockley RA. The cleavage specificity of an IgA1 protease from Haemophilus influenzae
. Virulence 2011;2:103-10.
Jalalvand F, Su YC, Mörgelin M, Brant M, Hallgren O, Westergren-Thorsson G, et al. Haemophilus influenzae
protein F mediates binding to laminin and human pulmonary epithelial cells. J Infect Dis 2013;207:803-13.
Kress-Bennett JM, Hiller NL, Eutsey RA, Powell E, Longwell MJ, Hillman T, et al
. Identification and characterization of msf, a novel virulence factor in Haemophilus influenzae
. PLoS One 2016;11:e0149891.
Pang B, Hong W, Kock ND, Swords WE. Dps promotes survival of nontypeable Haemophilus influenzae
in biofilm communities in vitro
and resistance to clearance in vivo
. Front Cell Infect Microbiol 2012;2:58.
Al-Jubair T, Mukherjee O, Oosterhuis S, Singh B, Su YC, Fleury C, et al. Haemophilus influenzae
type F hijacks vitronectin using protein H to resist host innate immunity and adhere to pulmonary epithelial cells. J Immunol 2015;195:5688-95.
Duell BL, Su YC, Riesbeck K. Host-pathogen interactions of nontypeable Haemophilus influenzae
: From commensal to pathogen. FEBS Lett 2016;590:3840-53.
Taylor SL, Rogers GB, Chen AC, Burr LD, McGuckin MA, Serisier DJ. Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis. Ann Am Thorac Soc 2015;12:701-7.
King PT, Sharma R, O′Sullivan K, Selemidis S, Lim S, Radhakrishna N, et al.
Nontypeable Haemophilus influenzae
induces sustained lung oxidative stress and protease expression. PLoS One 2015;10:e0120371.
Wurzel DF, Marchant JM, Yerkovich ST, Upham JW, Petsky HL, Smith-Vaughan H, et al.
Protracted bacterial bronchitis in children: Natural history and risk factors for bronchiectasis. Chest 2016;150:1101-8.
Roberts MC, Soge OO, No DB. Characterization of macrolide resistance genes in Haemophilus influenzae
isolated from children with cystic fibrosis. J Antimicrob Chemother 2011;66:100-4.
Atkinson CT, Kunde DA, Tristram SG. Acquired macrolide resistance genes in Haemophilus influenzae
? J Antimicrob Chemother 2015;70:2234-6.
Molina JM, Córdoba J, Esteban R, Laínez B, Monsoliu A, Gregori V, et al.
Study of the betalactam resistance of Haemophilus influenzae
conferred by the bla (ROB-1) gene. Rev Esp Quimioter 2002;15:148-51.
Pettigrew MM, Tsuji BT, Gent JF, Kong Y, Holden PN, Sethi S, et al.
Effect of fluoroquinolones and macrolides on eradication and resistance of Haemophilus influenzae
in chronic obstructive pulmonary disease. Antimicrob Agents Chemother 2016;60:4151-8.
Pérez-Vázquez M, Román F, García-Cobos S, Campos J. Fluoroquinolone resistance in Haemophilus influenzae
is associated with hypermutability. Antimicrob Agents Chemother 2007;51:1566-9.
Boyle-Vavra S, Daum RS. Community-acquired methicillin-resistant Staphylococcus aureus
: The role of Panton-Valentine leukocidin. Lab Invest 2007;87:3-9.
McNeil JC. Staphylococcus aureus
-antimicrobial resistance and the immunocompromised child. Infect Drug Resist 2014;7:117-27.
Trong HN, Prunier AL, Leclercq R. Hypermutable and fluoroquinolone-resistant clinical isolates of Staphylococcus aureus
. Antimicrob Agents Chemother 2005;49:2098-101.
Pozzi C, Waters EM, Rudkin JK, Schaeffer CR, Lohan AJ, Tong P, et al.
Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus
device-associated infections. PLoS Pathog 2012;8:e1002626.
Chekabab SM, Silverman RJ, Lafayette SL, Luo Y, Rousseau S, Nguyen D. Staphylococcus aureus
inhibits IL-8 responses induced by Pseudomonas aeruginosa
in airway epithelial cells. PLoS One 2015;10:e0137753.
Smith CM, Sandrini S, Datta S, Freestone P, Shafeeq S, Radhakrishnan P, et al.
Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae
by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. Am J Respir Crit Care Med 2014;190:196-207.
Lee JY, Song JH, Ko KS. Recombination rates of Streptococcus pneumoniae
isolates with both erm(B) and mef(A) genes. FEMS Microbiol Lett 2010;309:163-9.
Mostowy R, Croucher NJ, Hanage WP, Harris SR, Bentley S, Fraser C. Heterogeneity in the frequency and characteristics of homologous recombination in pneumococcal evolution. PLoS Genet 2014;10:e1004300.
de la Campa AG, Ferrandiz MJ, Tubau F, Pallarés R, Manresa F, Liñares J. Genetic characterization of fluoroquinolone-resistant Streptococcus pneumoniae
strains isolated during ciprofloxacin therapy from a patient with bronchiectasis. Antimicrob Agents Chemother 2003;47:1419-22.
Hare KM, Grimwood K, Chang AB, Chatfield MD, Valery PC, Leach AJ, et al.
Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo. Eur J Clin Microbiol Infect Dis 2015;34:2275-85.
Hirakata Y, Mizuta Y, Wada A, Kondoh A, Kurihara S, Izumikawa K, et al.
The first telithromycin-resistant Streptococcus pneumoniae
isolate in Japan associated with erm(B) and mutations in 23S rRNA and riboprotein L4. Jpn J Infect Dis 2007;60:48-50.
Sahuquillo-Arce JM, Selva M, Perpiñán H, Gobernado M, Armero C, López-Quílez A, et al.
Antimicrobial resistance in more than 100,000 Escherichia coli
isolates according to culture site and patient age, gender, and location. Antimicrob Agents Chemother 2011;55:1222-8.
Rodríguez-Baño J, Cisneros JM, Cobos-Trigueros N, Fresco G, Navarro-San Francisco C, Gudiol C, et al.
Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae
. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin 2015;33:337.e1-337.e21.
Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J Clin Microbiol 2014;52:2813-23.
Swenson CE, Sadikot RT. Achromobacter respiratory infections. Ann Am Thorac Soc 2015;12:252-8.
Grimwood K, Bell SC, Chang AB. Antimicrobial treatment of non-cystic fibrosis bronchiectasis. Expert Rev Anti Infect Ther 2014;12:1277-96.
Barker AF, Couch L, Fiel SB, Gotfried MH, Ilowite J, Meyer KC, et al.
Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa
density in bronchiectasis. Am J Respir Crit Care Med 2000;162(2 Pt 1):481-5.
Barker AF, O′Donnell AE, Flume P, Thompson PJ, Ruzi JD, de Gracia J, et al.
Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): Two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med 2014;2:738-49.
O′Donnell AE, Barker AF, Ilowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Chest 1998;113:1329-34.
Haworth CS, Bilton D, Elborn JS. Long-term macrolide maintenance therapy in non-CF bronchiectasis: Evidence and questions. Respir Med 2014;108:1397-408.
Haworth CS, Foweraker JE, Wilkinson P, Kenyon RF, Bilton D. Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas aeruginosa
infection. Am J Respir Crit Care Med 2014;189:975-82.
Hnin K, Nguyen C, Carson KV, Evans DJ, Greenstone M, Smith BJ. Prolonged antibiotics for non-cystic fibrosis bronchiectasis in children and adults. Cochrane Database Syst Rev 2015;8:CD001392.
Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: A systematic review. Eur Respir J 2014;44:382-93.
Serisier DJ, Bilton D, De Soyza A, Thompson PJ, Kolbe J, Greville HW, et al.
Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): A randomised, double-blind, placebo-controlled trial. Thorax 2013;68:812-7.
Welsh EJ, Evans DJ, Fowler SJ, Spencer S. Interventions for bronchiectasis: An overview of Cochrane systematic reviews. Cochrane Database Syst Rev 2015;7:CD010337.
Zarogoulidis P, Papanas N, Kioumis I, Chatzaki E, Maltezos E, Zarogoulidis K. Macrolides: From in vitro
anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. Eur J Clin Pharmacol 2012;68:479-503.
MacLeod DL, Barker LM, Sutherland JL, Moss SC, Gurgel JL, Kenney TF, et al.
Antibacterial activities of a fosfomycin/tobramycin combination: A novel inhaled antibiotic for bronchiectasis. J Antimicrob Chemother 2009;64:829-36.
Prina E, Ranzani OT, Polverino E, Cillóniz C, Ferrer M, Fernandez L, et al.
Risk factors associated with potentially antibiotic-resistant pathogens in community-acquired pneumonia. Ann Am Thorac Soc 2015;12:153-60.
Shorr AF, Myers DE, Huang DB, Nathanson BH, Emons MF, Kollef MH. A risk score for identifying methicillin-resistant Staphylococcus aureus
in patients presenting to the hospital with pneumonia. BMC Infect Dis 2013;13:268.
Ma HM, Ip M, Woo J, Hui DS, Lui GC, Lee NL, et al.
Risk factors for drug-resistant bacterial pneumonia in older patients hospitalized with pneumonia in a Chinese population. QJM 2013;106:823-9.
Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Shiraki A, et al.
Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med 2013;188:985-95.
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