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1.
mBio ; 15(2): e0314423, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38179971

RESUMEN

Persons with cystic fibrosis (CF), starting in early life, show intestinal microbiome dysbiosis characterized in part by a decreased relative abundance of the genus Bacteroides. Bacteroides is a major producer of the intestinal short chain fatty acid propionate. We demonstrate here that cystic fibrosis transmembrane conductance regulator-defective (CFTR-/-) Caco-2 intestinal epithelial cells are responsive to the anti-inflammatory effects of propionate. Furthermore, Bacteroides isolates inhibit the IL-1ß-induced inflammatory response of CFTR-/- Caco-2 intestinal epithelial cells and do so in a propionate-dependent manner. The introduction of Bacteroides-supplemented stool from infants with cystic fibrosis into the gut of CftrF508del mice results in higher propionate in the stool as well as the reduction in several systemic pro-inflammatory cytokines. Bacteroides supplementation also reduced the fecal relative abundance of Escherichia coli, indicating a potential interaction between these two microbes, consistent with previous clinical studies. For a Bacteroides propionate mutant in the mouse model, pro-inflammatory cytokine KC is higher in the airway and serum compared with the wild-type (WT) strain, with no significant difference in the absolute abundance of these two strains. Taken together, our data indicate the potential multiple roles of Bacteroides-derived propionate in the modulation of systemic and airway inflammation and mediating the intestinal ecology of infants and children with CF. The roles of Bacteroides and the propionate it produces may help explain the observed gut-lung axis in CF and could guide the development of probiotics to mitigate systemic and airway inflammation for persons with CF.IMPORTANCEThe composition of the gut microbiome in persons with CF is correlated with lung health outcomes, a phenomenon referred to as the gut-lung axis. Here, we demonstrate that the intestinal microbe Bacteroides decreases inflammation through the production of the short-chain fatty acid propionate. Supplementing the levels of Bacteroides in an animal model of CF is associated with reduced systemic inflammation and reduction in the relative abundance of the opportunistically pathogenic group Escherichia/Shigella in the gut. Taken together, these data demonstrate a key role for Bacteroides and microbially produced propionate in modulating inflammation, gut microbial ecology, and the gut-lung axis in cystic fibrosis. These data support the role of Bacteroides as a potential probiotic in CF.


Asunto(s)
Fibrosis Quística , Niño , Lactante , Humanos , Ratones , Animales , Fibrosis Quística/complicaciones , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Propionatos , Bacteroides/genética , Células CACO-2 , Inflamación/complicaciones , Modelos Animales de Enfermedad , Disbiosis/complicaciones , Escherichia coli
2.
mBio ; 12(5): e0209821, 2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34579569

RESUMEN

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex (Bcc), a group of bacteria with members responsible for causing lung infections in cystic fibrosis (CF) patients. The most severe outcome of Bcc infection in CF patients is cepacia syndrome, a disease characterized by necrotizing pneumonia with bacteremia and sepsis. B. cenocepacia is strongly associated with cepacia syndrome, making it one of the most virulent members of the Bcc. Mechanisms underlying the pathogenesis of B. cenocepacia in lung infections and cepacia syndrome remain to be uncovered. B. cenocepacia is primarily an intracellular pathogen and encodes the type VI secretion system (T6SS) effector TecA, which is translocated into host phagocytes. TecA is a deamidase that inactivates multiple Rho GTPases, including RhoA. Inactivation of RhoA by TecA triggers assembly of the pyrin inflammasome, leading to secretion of proinflammatory cytokines, such as interleukin-1ß, from macrophages. Previous work with the B. cenocepacia clinical isolate J2315 showed that TecA increases immunopathology during acute lung infection in C57BL/6 mice and suggested that this effector acts as a virulence factor by triggering assembly of the pyrin inflammasome. Here, we extend these results using a second B. cenocepacia clinical isolate, AU1054, to demonstrate that TecA exacerbates weight loss and lethality during lung infection in C57BL/6 mice and mice engineered to have a CF genotype. Unexpectedly, pyrin was dispensable for TecA virulence activity in both mouse infection models. Our findings establish that TecA is a B. cenocepacia virulence factor that exacerbates lung inflammation, weight loss, and lethality in mouse infection models. IMPORTANCE B. cenocepacia is often considered the most virulent species in the Bcc because of its close association with cepacia syndrome in addition to its capacity to cause chronic lung infections in CF patients (1). Prior to the current study, virulence factors of B. cenocepacia important for causing lethal disease had not been identified in a CF animal model of lung infection. Results of this study describe a CF mouse model and its use in demonstrating that the T6SS effector TecA of B. cenocepacia exacerbates inflammatory cell recruitment and weight loss and is required for lethality and, thus, acts as a key virulence factor during lung infection. This model will be important in further studies to better understand TecA's role as a virulence factor and in investigating ways to prevent or treat B. cenocepacia infections in CF patients. Additionally, TecA may be the founding member of a family of virulence factors in opportunistic pathogens.


Asunto(s)
Proteínas Bacterianas/metabolismo , Infecciones por Burkholderia/microbiología , Burkholderia cenocepacia/metabolismo , Pulmón/microbiología , Sistemas de Secreción Tipo VI/metabolismo , Factores de Virulencia/metabolismo , Animales , Proteínas Bacterianas/genética , Burkholderia cenocepacia/genética , Fibrosis Quística/microbiología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Sistemas de Secreción Tipo VI/genética , Factores de Virulencia/genética
3.
mBio ; 12(5): e0176321, 2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34544277

RESUMEN

A recent workshop titled "Developing Models to Study Polymicrobial Infections," sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 35+ investigators over two virtual sessions. Here, we present the findings of this workshop, summarize some of the challenges involved with developing such models, and suggest three frameworks to tackle this complex problem. The frameworks proposed here, we believe, could be generally useful in developing new model systems for other infectious diseases. Developing and validating new approaches to study the complex polymicrobial communities in the CF airway could open windows to new therapeutics to treat these recalcitrant infections, as well as uncovering organizing principles applicable to chronic polymicrobial infections more generally.


Asunto(s)
Coinfección/complicaciones , Fibrosis Quística/complicaciones , Modelos Biológicos , Infección Persistente/complicaciones , Animales , Biopelículas , Humanos , Interacciones Microbianas , Sistema Respiratorio/microbiología
4.
J Bacteriol ; 201(8)2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30718303

RESUMEN

Cystic fibrosis (CF) is a genetic disease that causes patients to accumulate thick, dehydrated mucus in the lung and develop chronic, polymicrobial infections due to reduced mucociliary clearance. These chronic polymicrobial infections and subsequent decline in lung function are significant factors in the morbidity and mortality of CF. Pseudomonas aeruginosa and Streptococcus spp. are among the most prevalent organisms in the CF lung; the presence of P. aeruginosa correlates with lung function decline, and the Streptococcus milleri group (SMG), a subgroup of the viridans streptococci, is associated with exacerbations in patients with CF. Here we characterized the interspecies interactions that occur between these two genera. We demonstrated that multiple P. aeruginosa laboratory strains and clinical CF isolates promote the growth of multiple SMG strains and oral streptococci in an in vitro coculture system. We investigated the mechanism by which P. aeruginosa enhances growth of streptococci by screening for mutants of P. aeruginosa PA14 that are unable to enhance Streptococcus growth, and we identified the P. aeruginosapqsL::TnM mutant, which failed to promote growth of Streptococcus constellatus and S. sanguinis Characterization of the P. aeruginosa ΔpqsL mutant revealed that this strain cannot promote Streptococcus growth. Our genetic data and growth studies support a model whereby the P. aeruginosa ΔpqsL mutant overproduces siderophores and thus likely outcompetes Streptococcus sanguinis for limited iron. We propose a model whereby competition for iron represents one important means of interaction between P. aeruginosa and Streptococcus spp.IMPORTANCE Cystic fibrosis (CF) lung infections are increasingly recognized for their polymicrobial nature. These polymicrobial infections may alter the biology of the organisms involved in CF-related infections, leading to changes in growth, virulence, and/or antibiotic tolerance, and could thereby affect patient health and response to treatment. In this study, we demonstrate interactions between P. aeruginosa and streptococci using a coculture model and show that one interaction between these microbes is likely competition for iron. Thus, these data indicate that one CF pathogen may influence the growth of another, and they add to our limited knowledge of polymicrobial interactions in the CF airway.


Asunto(s)
Proteínas Bacterianas/metabolismo , Interacciones Microbianas , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/metabolismo , Sideróforos/metabolismo , Streptococcus milleri (Grupo)/efectos de los fármacos , Streptococcus milleri (Grupo)/crecimiento & desarrollo , Proteínas Bacterianas/genética , Eliminación de Gen , Pruebas Genéticas , Hierro/metabolismo , Mutagénesis Insercional , Pseudomonas aeruginosa/genética
5.
Clin Infect Dis ; 67(6): 813-816, 2018 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-30169655

RESUMEN

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

6.
Otol Neurotol ; 39(9): e837-e842, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30199500

RESUMEN

OBJECTIVE: Ciprofloxacin resistance has been reported in 4.5% of patients with otorrhea and is increasing in prevalence. Due to ototoxicity, only fluoroquinolones are Food and Drug Administration approved for topical therapy in the middle ear. Furthermore, there is an assumption that antibiotic resistance is less relevant to topical therapy due to in vivo concentrations much higher than the minimum inhibitory concentration used to determine resistance. This study investigates ciprofloxacin-resistant infections and seeks to develop a better understanding of treatment options and outcomes. STUDY DESIGN: Retrospective review of 141 ciprofloxacin-resistant otologic infections. SETTING: Tertiary-care hospital. PATIENTS: Patients with culture-proven ciprofloxacin-resistant infections from 2008 to 2017. INTERVENTION(S): Antibiotic treatment with ciprofloxacin topical drops, ciprofloxacin plus oral antibiotics, and nonciprofloxacin therapy. MAIN OUTCOME MEASURE(S): Bacteriology for ciprofloxacin-resistant infections and treatment effectiveness of various therapies. RESULTS: Methicillin-resistant Staphylococcus aureus (33%), Corynebacterium striatum (19%), and non-Methicillin-resistant Staphylococcus aureus (11%) are the most frequent causes of ciprofloxacin-resistant infections. Topical ciprofloxacin monotherapy was successful in 2.7% of infections compared with a 64.7% success rate with the addition of an oral antibiotic (p < 0.001). Nonciprofloxacin drops are more effective with a 70% cure rate compared with the 2.7% of the ciprofloxacin drops p < 0.001. There was no difference in treatment efficacy when comparing nonciprofloxacin topical therapy (70% cure) to nonciprofloxacin topical therapy plus oral antibiotic (83% cure, p = 0.17). CONCLUSIONS: Using ciprofloxacin drops to treat ciprofloxacin-resistant bacteria is ineffective and patients do significantly better with alternative therapy. This finding supports the conclusion that high concentrations achieved in topical applications are not sufficient to overcome antibiotic resistance.


Asunto(s)
Antibacterianos/uso terapéutico , Ciprofloxacina/uso terapéutico , Farmacorresistencia Microbiana/efectos de los fármacos , Otitis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Humanos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Ventilación del Oído Medio , Estudios Retrospectivos , Resultado del Tratamiento
7.
mSphere ; 3(4)2018 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-30089648

RESUMEN

Here, we report an approach to detect diverse bacterial and fungal taxa in complex samples by direct analysis of community RNA in one step using NanoString probe sets. We designed rRNA-targeting probe sets to detect 42 bacterial and fungal genera or species common in cystic fibrosis (CF) sputum and demonstrated the taxon specificity of these probes, as well as a linear response over more than 3 logs of input RNA. Culture-based analyses correlated qualitatively with relative abundance data on bacterial and fungal taxa obtained by NanoString, and the analysis of serial samples demonstrated the use of this method to simultaneously detect bacteria and fungi and to detect microbes at low abundance without an amplification step. Compared at the genus level, the relative abundances of bacterial taxa detected by analysis of RNA correlated with the relative abundances of the same taxa as measured by sequencing of the V4V5 region of the 16S rRNA gene amplified from community DNA from the same sample. We propose that this method may complement other methods designed to understand dynamic microbial communities, may provide information on bacteria and fungi in the same sample with a single assay, and with further development, may provide quick and easily interpreted diagnostic information on diverse bacteria and fungi at the genus or species level.IMPORTANCE Here we demonstrate the use of an RNA-based analysis of specific taxa of interest, including bacteria and fungi, within microbial communities. This multiplex method may be useful as a means to identify samples with specific combinations of taxa and to gain information on how specific populations vary over time and space or in response to perturbation. A rapid means to measure bacterial and fungal populations may aid in the study of host response to changes in microbial communities.


Asunto(s)
Bacterias/clasificación , Biota , Fibrosis Quística/microbiología , Hongos/clasificación , ARN Bacteriano/genética , ARN de Hongos/genética , Esputo/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , Hongos/genética , Hongos/aislamiento & purificación , Humanos , Sondas de Oligonucleótidos/genética , ARN Bacteriano/análisis , ARN de Hongos/análisis , ARN Ribosómico/análisis , ARN Ribosómico/genética , Análisis de Secuencia de ADN
8.
Clin Infect Dis ; 67(6): e1-e94, 2018 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-29955859

RESUMEN

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/normas , Enfermedades Transmisibles/diagnóstico , Control de Enfermedades Transmisibles , Enfermedades Transmisibles/microbiología , Humanos , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Sociedades Científicas , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/microbiología , Manejo de Especímenes , Estados Unidos
9.
Cytojournal ; 15: 5, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29531572

RESUMEN

Cokeromyces recurvatus is a zygomycetes yeast form that is very rarely detected in Papanicolaou (Pap) tests, in which it typically represents an innocuous colonizer. Its morphology closely resembles that of the better known Paracoccidioides brasiliensis, which can disseminate widely and cause clinically significant disease. We present a case of C. recurvatus detected in a cervical liquid-based preparation obtained from a 38-year old healthy woman. Careful cytomorphologic evaluation, in combination with culture and molecular techniques, was utilized to make a diagnosis and prevent the misdiagnosis of P. brasiliensis.

10.
J Breath Res ; 12(2): 026001, 2018 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-28952968

RESUMEN

The identification of pathogen-specific volatile metabolic 'fingerprints' could lead to the rapid identification of disease-causing organisms either directly from ex vivo patient bio-specimens or from in vitro cultures. In the present study, we have evaluated the volatile metabolites produced by 100 clinical isolates belonging to ten distinct pathogen groups that, in aggregate, account for 90% of bloodstream infections, 90% of urinary tract infections, and 80% of infections encountered in the intensive care unit setting. Headspace volatile metabolites produced in vitro were concentrated using headspace solid-phase microextraction and analyzed via two-dimensional gas chromatography time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS). A total of 811 volatile metabolites were detected across all samples, of which 203 were: (1) detected in 9 or 10 (of 10) isolates belonging to one or more pathogen groups, and (2) significantly more abundant in cultures relative to sterile media. Network analysis revealed a distinct metabolic fingerprint associated with each pathogen group, and analysis via Random Forest using leave-one-out cross-validation resulted in a 95% accuracy for the differentiation between groups. The present findings support the results of prior studies that have reported on the differential production of volatile metabolites across pathogenic bacteria and fungi, and provide additional insight through the inclusion of pathogen groups that have seldom been studied previously, including Acinetobacter spp., coagulase-negative Staphylococcus, and Proteus mirabilis, as well as the utilization of HS-SPME-GC×GC-TOFMS for improved sensitivity and resolution relative to traditional gas chromatography-based techniques.


Asunto(s)
Bacterias/metabolismo , Hongos/metabolismo , Metabolómica/métodos , Compuestos Orgánicos Volátiles/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Metaboloma , Análisis de Componente Principal
11.
J Cutan Pathol ; 44(4): 373-375, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28000235

RESUMEN

Dirofilaria species are roundworms responsible for "heartworm" in canines. On occasion, humans are an accidental host, resulting in pulmonary (Dirofilaria immitis) or extrapulmonary (Dirofilaria repens) manifestations. Of the extrapulmonary sites of involvement, subcutaneous involvement is particularly common. We report a case of a 49-year-old female who presented with an erythematous nodule on her shin, which closely resembled necrobiosis lipoidica on histopathologic examination. On closer examination, there were foci of necrosis that harbored segments of the nematode, diagnostic of dirofiliarisis. We present this case to highlight the histopathologic similarities and differences between palisaded necrobiotic conditions and this potentially underrecognized entity.


Asunto(s)
Dermatitis , Dirofilaria repens , Dirofilariasis , Enfermedades Cutáneas Parasitarias , Animales , Dermatitis/parasitología , Dermatitis/patología , Dirofilariasis/parasitología , Dirofilariasis/patología , Femenino , Humanos , Persona de Mediana Edad , Enfermedades Cutáneas Parasitarias/parasitología , Enfermedades Cutáneas Parasitarias/patología
12.
Microb Ecol ; 68(1): 111-20, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24435545

RESUMEN

Pseudomonas aeruginosa, a ubiquitous environmental organism, is a difficult-to-treat opportunistic pathogen due to its broad-spectrum antibiotic resistance and its ability to form biofilms. In this study, we investigate the link between resistance to a clinically important antibiotic, imipenem, and biofilm formation. First, we observed that the laboratory strain P. aeruginosa PAO1 carrying a mutation in the oprD gene, which confers resistance to imipenem, showed a modest reduction in biofilm formation. We also observed an inverse relationship between imipenem resistance and biofilm formation for imipenem-resistant strains selected in vitro, as well as for clinical isolates. We identified two clinical isolates of P. aeruginosa from the sputum of cystic fibrosis patients that formed robust biofilms, but were sensitive to imipenem (MIC ≤ 2 µg/ml). To test the hypothesis that there is a general link between imipenem resistance and biofilm formation, we performed transposon mutagenesis of these two clinical strains to identify mutants defective in biofilm formation, and then tested these mutants for imipenem resistance. Analysis of the transposon mutants revealed a role for previously described biofilm factors in these clinical isolates of P. aeruginosa, including mutations in the pilY1, pilX, pilW, algC, and pslI genes, but none of the biofilm-deficient mutants became imipenem resistant (MIC ≥ 8 µg/ml), arguing against a general link between biofilm formation and resistance to imipenem. Thus, assessing biofilm formation capabilities of environmental isolates is unlikely to serve as a good predictor of imipenem resistance. We also discuss our findings in light of the limited literature addressing planktonic antibiotic resistance factors that impact biofilm formation.


Asunto(s)
Antibacterianos/farmacología , Biopelículas , Farmacorresistencia Bacteriana/genética , Imipenem/farmacología , Porinas/genética , Pseudomonas aeruginosa/efectos de los fármacos , Fibrosis Quística/microbiología , Genes Bacterianos , Humanos , Mutación , Porinas/fisiología , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiología , Esputo/microbiología
13.
Clin Infect Dis ; 57(4): 485-8, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23881727

RESUMEN

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Enfermedades Transmisibles/diagnóstico , Humanos , Estados Unidos
14.
Clin Infect Dis ; 57(4): e22-e121, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23845951

RESUMEN

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Enfermedades Transmisibles/diagnóstico , Humanos , Estados Unidos
15.
J Antimicrob Chemother ; 67(11): 2673-81, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22843834

RESUMEN

OBJECTIVES: Aztreonam for inhalation solution (AZLI) was recently approved by the FDA for treating cystic fibrosis (CF) patients infected with Pseudomonas aeruginosa. Here we investigated the effect of aztreonam alone or in combination with tobramycin on P. aeruginosa biofilms grown on CF airway epithelial cells. METHODS: P. aeruginosa biofilms, produced by laboratory strains or clinical isolates, were formed on confluent CF airway cells before treatment overnight with aztreonam or tobramycin alone or in combination. Alternatively, antibiotics were added 1 h after bacterial inoculation to assess their ability to impair biofilm formation at 5 h. Bacterial cfu remaining after treatment were then determined by plate counting. RESULTS: In the absence of antibiotics, all strains developed biofilms that disrupted CF airway epithelial monolayers overnight. Tobramycin reduced the cfu of all strains grown as biofilms. Aztreonam reduced the cfu of some strains by ∼1 log unit without preserving the integrity of cystic fibrosis airway cell monolayers, while decreasing the biofilms of other clinical isolates by ∼4 log units and protecting the monolayers from being compromised. The combination of aztreonam and tobramycin reduced the cfu of two strains by an additional 0.5 and 2 log units, respectively. Of all the mechanisms explored, Psl exopolysaccharide production might explain the variations in biofilm tolerance to aztreonam in some of the strains. CONCLUSIONS: Effects of aztreonam on P. aeruginosa biofilms in the in vitro co-culture model are strain-dependent. The simultaneous application of aztreonam and tobramycin may be beneficial for a subset of CF patients by eliminating susceptible P. aeruginosa strains.


Asunto(s)
Antibacterianos/farmacología , Aztreonam/farmacología , Biopelículas/efectos de los fármacos , Células Epiteliales/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/farmacología , Fibrosis Quística/complicaciones , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/fisiología , Factores de Tiempo
17.
Infect Immun ; 78(10): 4384-91, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20696829

RESUMEN

The expression of virulence factors in Staphylococcus aureus is tightly coordinated by a vast network of regulatory molecules. In this report, we characterize a genetic locus unique to staphylococci called rsr that has a role in repressing two key virulence regulators, sarR and agr. Using strain SH1000, we showed that the transcription of virulence effectors, such as hla, sspA, and spa, is altered in an rsr mutant in a way consistent with agr upregulation. Analysis of RNAIII expression of the agr locus in rsr and rsr-sarR mutants indicated that rsr likely contributes to agr expression independently of SarR. We also provide evidence using a murine model of S. aureus skin infection that the effects mediated by rsr reduce disease progression.


Asunto(s)
Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica/fisiología , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Transactivadores/metabolismo , Animales , Proteínas Bacterianas/genética , Ligamiento Genético , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Bacteriano/genética , ARN Bacteriano/metabolismo , Infecciones Cutáneas Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Transactivadores/genética , Transcripción Genética , Virulencia , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
18.
Infect Dis Rep ; 2(1)2010 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-21709740

RESUMEN

We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT). To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

19.
J Clin Microbiol ; 48(2): 609-11, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20007392
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