化脓性中耳炎病原菌感染的研究进展

化脓性中耳炎是耳鼻喉科临床常见疾病,可导致听力下降、鼓膜充血、鼓膜穿孔、耳鸣、耳痛及流脓等。化脓性中耳炎主要由微生物进入中耳引起感染,使中耳黏膜发生化脓性病变,且不同患者感染的病原菌不同。本文从化脓性中耳炎的发病机制、病原菌及其耐药性和治疗方法等几个方面进行综述,以期为临床化脓性中耳炎的诊断及合理用药提供参考。     

Identification of biofilm proteins in non-typeable Haemophilus Influenzae

Background  

Non-typeable Haemophilus influenzae biofilm formation is implicated in a number of chronic infections including otitis media, sinusitis and bronchitis. Biofilm structure includes cells and secreted extracellular matrix that is "slimy" and believed to contribute to the antibiotic resistant properties of biofilm bacteria. Components of biofilm extracellular matrix are largely unknown. In order to identify such biofilm proteins an ex-vivo biofilm of a non-typeable Haemophilus influenzae isolate, originally from an otitis media patent, was produced by on-filter growth. Extracellular matrix fraction was subjected to proteomic analysis via LC-MS/MS to identify proteins.     

Anaerobic bacteria in upper respiratory tract and head and neck infections: microbiology and treatment

Anaerobes are the predominant components of oropharyngeal mucous membranes bacterial flora, and are therefore a common cause of bacterial infections of endogenous origin of upper respiratory tract and head and neck. This review summarizes the aerobic and anaerobic microbiology and antimicrobials therapy of these infections. These include acute and chronic otitis media, mastoiditis and sinusitis, pharyngo-tonsillitis, peritonsillar, retropharyngeal and parapharyngeal abscesses, suppurative thyroiditis, cervical lymphadenitis, parotitis, siliadenitis, and deep neck infections including Lemierre Syndrome. The recovery from these infections depends on prompt and proper medical and when indicated also surgical management.     

Respiratory Infections in Adults with Atopic Disease and IgE Antibodies to Common Aeroallergens

Background

Atopic diseases, including allergic rhinitis, allergic dermatitis and asthma, are common diseases with a prevalence of 30–40% worldwide and are thus of great global public health importance. Allergic inflammation may influence the immunity against infections, so atopic individuals could be susceptible to respiratory infections. No previous population-based study has addressed the relation between atopy and respiratory infections in adulthood. We assessed the relation between atopic disease, specific IgE antibodies and the occurrence of upper and lower respiratory infections in the past 12 months among working-aged adults.

Methods and Findings

A population-based cross-sectional study of 1008 atopic and non-atopic adults 21–63 years old was conducted. Information on atopic diseases, allergy tests and respiratory infections was collected by a questionnaire. Specific IgE antibodies to common aeroallergens were measured in serum. Adults with atopic disease had a significantly increased risk of lower respiratory tract infections (LRTI; including acute bronchitis and pneumonia) with an adjusted risk ratio (RR) 2.24 (95% confidence interval [CI] 1.43, 3.52) and upper respiratory tract infections (URTI; including common cold, sinusitis, tonsillitis, and otitis media) with an adjusted RR 1.55 (1.14, 2.10). The risk of LRTIs increased with increasing level of specific IgE (linear trend P = 0.059).

Conclusions

This study provides new evidence that working-aged adults with atopic disease experience significantly more LRTIs and URTIs than non-atopics. The occurrence of respiratory infections increased with increasing levels of specific IgE antibodies to common aeroallergens, showing a dose-response pattern with LRTIs. From the clinical point of view it is important to recognize that those with atopies are a risk group for respiratory infections, including more severe LRTIs.     

The role of the local microbial ecosystem in respiratory health and disease

Respiratory tract infections are a major global health concern, accounting for high morbidity and mortality, especially in young children and elderly individuals. Traditionally, highly common bacterial respiratory tract infections, including otitis media and pneumonia, were thought to be caused by a limited number of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. However, these pathogens are also frequently observed commensal residents of the upper respiratory tract (URT) and form—together with harmless commensal bacteria, viruses and fungi—intricate ecological networks, collectively known as the ‘microbiome’. Analogous to the gut microbiome, the respiratory microbiome at equilibrium is thought to be beneficial to the host by priming the immune system and providing colonization resistance, while an imbalanced ecosystem might predispose to bacterial overgrowth and development of respiratory infections. We postulate that specific ecological perturbations of the bacterial communities in the URT can occur in response to various lifestyle or environmental effectors, leading to diminished colonization resistance, loss of containment of newly acquired or resident pathogens, preluding bacterial overgrowth, ultimately resulting in local or systemic bacterial infections. Here, we review the current body of literature regarding niche-specific upper respiratory microbiota profiles within human hosts and the changes occurring within these profiles that are associated with respiratory infections.     

Immunity to antigens of nontypeable Haemophilus influenzae strains

Nonencapsulated (nontypeable) Haemophilus influenzae (NTHi) is a Gram-negative coccobacillus colonizing upper respiratory tract of most healthy people and causing such diseases as otitis media, sinusitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. NTHi may cause systemic infection. As a result, over the past decade the bacterium has been the subject of intense research. However immune response to NTHi has not been well characterized. Data on research of immune response to NTHi are presented.     

Treatment of acute otitis media: a controlled study of 142 children

Results of the use of ampicillin, penicillin G and symptomatic therapy in the treatment of acute otitis media in 142 children were compared. Antibiotic therapy conveyed significant benefit. No major differences were observed between penicillin and ampicillin, except in the age group under 3 years where ampicillin was associated with the best results. Ampicillin appears to be the drug of choice. Its superiority over symptomatic therapy was statistically significant. Long-term sequelae were not observed in any of the three treatment groups. The relative merits of erythromycin and ampicillin require further study.     

Dr. Mary Fanning: caring for AIDS patients at Toronto General.

Although amoxicillin has long been the preferred drug for treatment of acute otitis media, resistant strains of two relatively common causal organisms have emerged, prompting a search for other antibiotics. We performed a randomized double-blind trial comparing amoxicillin and trimethoprim-sulfamethoxazole in 221 children in whom acute otitis media was diagnosed in an outpatient setting. Diagnosis was on the basis of symptoms, otoscopic examination and acoustic reflectometry. No culture specimens were taken. A research nurse, using the same methods, evaluated patients in a follow-up home visit at around 14 days and measured compliance by examination of the medicine bottle. Equal proportions of children in the two groups were cured or improved (88% and 87%). Therapeutic efficacy was related to compliance in both groups, and there were few side effects in either group. This study had statistical power of 80% to detect a difference of 15%. We conclude that trimethoprim-sulfamethoxazole can be considered a first-line antibiotic in the treatment of acute otitis media.     

Pasteurella multocida infection in man; a review of the literature

Pasteurella multocida has been isolated from infected lesions of nearly all regions of the body. Cat and dog bite wounds are frequently infected by this organism. The severity of the lesion varies from trivial sepsis to a severe wound abscess with sloughing and septicaemia. Bone involvement is frequent. Despite the apparent sensitivity of the organism to a wide range of antibiotics, chemotherapy may be of little avail. Frequently, extensive débridement and skin grafting is required. In the respiratory tract, the clinical picture extends over bronchitis, bronchiectasis, pneumonia, empyema, otitis media, mastoiditis and sinusitis. In these latter infections a history of contact with animals may not be elicited. Examination of the patient's serum may not be helpful as antibody titers are often low, even in the presence of severe acute infection.     

Otitis Media Impacts Hundreds of Mouse Middle and Inner Ear Genes

Objective

Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.

Methods

To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes.

Results

Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear.

Conclusion

Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.     

Antibiotics in bacterial acute respiratory tract infection in children]

The data on changes in the susceptibility of the most frequent respiratory tract pathogens i.e. Pneumococcus spp. and Haemophilus influenzae within the last 15 years and Streptococcus spp., Staphylococcus spp. and Moraxella spp. at the present time as well as recommendations based on the original and some literature data on the choice of the antibacterial drugs for the initial treatment of bacterial complications of acute respiratory tract viral infections such as otitis, sinusitis and pharyngitis are presented. The necessity of decreasing the unjustified use of antibiotics in cases of uncomplicated acute respiratory tract viral infections is indicated.     

Comparison of Four Agar Plating Media with and Without Added Novobiocin for Isolation of Salmonellae from Beef and Deboned Poultry Meat

Four plating media, Hektoen enteric (HE), xylose-lysine deoxycholate (XLD), tryptic soy-xylose-lysine (TSXL), and tryptic soy-brillant green (TSBG) agars with and without 10 mg of added novobiocin per ml, were evaluated for recovery of Salmonella from roast beef and deboned turkey. Colonies producing a reaction typical of H₂S-positive salmonellae (alkaline with black centers) were picked. On the media without novobiocin, from 109 determinations on 75 samples, number of salmonellae found and false-positives were, respectively: HE—13, 58; XLD—17, 18; TSXL—23, 0; TSBG—22, 7. When novobiocin was present the corresponding results were: HE—17, 24; XLD—21, 2; TSXL—23, 3; TSBG—20, 7. A total of 25 determinations were positive on one or more agars. False-positives on HE and XLD without novobiocin were predominantly Proteus, which were almost totally eliminated by addition of 10 mg of novobiocin per liter. If alkaline H₂S-negative colonies had been considered, many more false-positives would have been found on HE and XLD but not on TSBG or TSXL. Addition of novobiocin markedly improved isolations of salmonellae from XLD and HE and reduced the number of false-positives. Addition of novobiocin did not improve performance of TSXL and slightly impaired differentiation of salmonellae from Citrobacter on TSBG. XLD with novobiocin and TSXL are highly specific for H₂S-positive salmonellae, and the appearance of Salmonella-like colonies on these media can be considered a presumptive test for H₂S-positive salmonellae.     

Primary ciliary dyskinesia.

Primary ciliary dyskinesia represents a group of heritable disorders of cilia and sperm affecting between 1 in 15,000 and 1 in 30,000 persons. Those affected lack measurable mucociliary clearance and suffer the constant misery of rhinorrhea and chronic productive cough. Because mucociliary clearance constitutes one of the respiratory system''s major lines of defense, these patients are vulnerable to chronic sinusitis, bronchitis, pneumonia, and otitis media. Left untreated, these problems may progress to bronchiectasis, found frequently in adult patients, or pulmonary hypertension with eventual cor pulmonale. Screening for this disorder includes some simple and inexpensive methods as well as more exotic techniques requiring special camera equipment and an electron microscope to make a definitive diagnosis. Physiotherapy techniques can be taught to patients with primary ciliary dyskinesia and go a long way toward making up for the lack of mucociliary clearance. Vigorous bronchopulmonary toilet and palliative measures may enable these patients to enjoy relatively normal lives.     

Adaptive Landscape by Environment Interactions Dictate Evolutionary Dynamics in Models of Drug Resistance

The adaptive landscape analogy has found practical use in recent years, as many have explored how their understanding can inform therapeutic strategies that subvert the evolution of drug resistance. A major barrier to applications of these concepts is a lack of detail concerning how the environment affects adaptive landscape topography, and consequently, the outcome of drug treatment. Here we combine empirical data, evolutionary theory, and computer simulations towards dissecting adaptive landscape by environment interactions for the evolution of drug resistance in two dimensions—drug concentration and drug type. We do so by studying the resistance mediated by Plasmodium falciparum dihydrofolate reductase (DHFR) to two related inhibitors—pyrimethamine and cycloguanil—across a breadth of drug concentrations. We first examine whether the adaptive landscapes for the two drugs are consistent with common definitions of cross-resistance. We then reconstruct all accessible pathways across the landscape, observing how their structure changes with drug environment. We offer a mechanism for non-linearity in the topography of accessible pathways by calculating of the interaction between mutation effects and drug environment, which reveals rampant patterns of epistasis. We then simulate evolution in several different drug environments to observe how these individual mutation effects (and patterns of epistasis) influence paths taken at evolutionary “forks in the road” that dictate adaptive dynamics in silico. In doing so, we reveal how classic metrics like the IC₅₀ and minimal inhibitory concentration (MIC) are dubious proxies for understanding how evolution will occur across drug environments. We also consider how the findings reveal ambiguities in the cross-resistance concept, as subtle differences in adaptive landscape topography between otherwise equivalent drugs can drive drastically different evolutionary outcomes. Summarizing, we discuss the results with regards to their basic contribution to the study of empirical adaptive landscapes, and in terms of how they inform new models for the evolution of drug resistance.     

Use of a Novel Fluorinated Organosulfur Compound To Isolate Bacteria Capable of Carbon-Sulfur Bond Cleavage

The vacuum residue fraction of heavy crudes contributes to the viscosity of these oils. Specific microbial cleavage of C—S bonds in alkylsulfide bridges that form linkages in this fraction may result in dramatic viscosity reduction. To date, no bacterial strains have been shown conclusively to cleave C—S bonds within alkyl chains. Screening for microbes that can perform this activity was greatly facilitated by the use of a newly synthesized compound, bis-(3-pentafluorophenylpropyl)-sulfide (PFPS), as a novel sulfur source. The terminal pentafluorinated aromatic rings of PFPS preclude growth of aromatic ring-degrading bacteria but allow for selective enrichment of strains capable of cleaving C—S bonds. A unique bacterial strain, Rhodococcus sp. strain JVH1, that used PFPS as a sole sulfur source was isolated from an oil-contaminated environment. Gas chromatography-mass spectrometry analysis revealed that JVH1 oxidized PFPS to a sulfoxide and then a sulfone prior to cleaving the C—S bond to form an alcohol and, presumably, a sulfinate from which sulfur could be extracted for growth. Four known dibenzothiophene-desulfurizing strains, including Rhodococcus sp. strain IGTS8, were all unable to cleave the C—S bond in PFPS but could oxidize PFPS to the sulfone via the sulfoxide. Conversely, JVH1 was unable to oxidize dibenzothiophene but was able to use a variety of alkyl sulfides, in addition to PFPS, as sole sulfur sources. Overall, PFPS is an excellent tool for isolating bacteria capable of cleaving subterminal C—S bonds within alkyl chains. The type of desulfurization displayed by JVH1 differs significantly from previously described reaction results.     

Affinity Distance Values among Somatic Metaphase Chromosomes in Maize

In maize root-tip metaphase preparations, all distances between two chromosomes were measured in 50 cells from each of seven stocks and in 30 from one stock; four were arrested with cold, two with 8-hydroxyquinoline, one with colchicine and one with monobromonaphthalene. Standardized, affinity-distance values were calculated for all pairs of homologues and pairs of nonhomologues from each preparation. The homologues of pair X were the least separated, those of pair I the most separated in the cold-arrested stocks. All but pairs I and VIII were shown to be significantly different from the observed mean. The observed mean was less than but not significantly different from the theoretical value for a random distribution. The use of chemical agents for metaphase arrest increased the separation of homologues, except for pair I.—Eleven percent of the comparisons of nonhomologues from cold-arrested, as contrasted to none of the comparisons from the c-metaphase treatments, were significantly different from the theoretical value for a random distribution. This was considered evidence for limited primary nonhomologue association in maize. Although there were specific, differential responses to the two arrest agents, the population of homologous pairs approached a random distribution only in chemically arrested stocks.—Primary homologue association was considered to be maintained by two mechanisms, the more common involving the microtubules and the second involving the nucleolus.—Interpretations are offered regarding the claims of somatic association in other species, especially man. The opportunity in maize for experimentally modifying distance values by cytogenetic techniques is discussed.     

Risk Factors for Chronic and Recurrent Otitis Media–A Meta-Analysis

Risk factors associated with chronic otitis media (COM) and recurrent otitis media (ROM) have been investigated in previous studies. The objective of this study was to integrate the findings and determine the possible risk factors for COM/ROM based on our meta-analysis. A comprehensive search of electronic bibliographic databases (PubMed, Embase, CNKI and Wanfang database) from 1964 to Dec 2012, as well as a manual search of references of articles, was performed. A total of 2971 articles were searched, and 198 full-text articles were assessed for eligibility; 24 studies were eligible for this meta-analysis. Regarding risk factors for COM/ROM, there were two to nine different studies from which the odds ratios (ORs) could be pooled. The presence of allergy or atopy increased the risk of COM/ROM (OR, 1.36; 95% CI, 1.13–1.64; P = 0.001). An upper respiratory tract infection (URTI) significantly increased the risk of COM/ROM (OR, 6.59; 95% CI, 3.13–13.89; P<0.00001). Snoring appeared to be a significant risk factor for COM/ROM (OR, 1.96; 95% CI, 1.78–2.16; P<0.00001). A patient history of acute otitis media (AOM)/ROM increased the risk of COM/ROM (OR, 11.13; 95% CI, 1.06–116.44; P = 0.04). Passive smoke significantly increased the risk of COM/ROM (OR, 1.39; 95% CI, 1.02–1.89 P = 0.04). Low social status appeared to be a risk factor for COM/ROM (OR, 3.82; 95% CI, 1.11–13.15; P = 0.03). Our meta-analysis identified reliable conclusions that allergy/atopy, URTI, snoring, previous history of AOM/ROM, Second-hand smoke and low social status are important risk factors for COM/ROM. Other unidentified risk factors need to be identified in further studies with critical criteria.     

Colonization and turnover of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in otitis-prone children

Recurrent otitis media are frequently intractable during childhood. It is unclear whether recurrent otitis media is caused by etiological bacteria colonization or by new infections. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were isolated from the nasopharynx of 7 otitisprone and 2 non-prone children with recurrent otitis media. Plural bacterial species and strains were found in all children while affected by otitis media. The same strain was repeatedly isolated from all otitisprone children even after administration of antibiotics but was not from the non-prone children. Antibiotic susceptibility did not differ significantly among the same repeatedly isolated strains. This pilot study suggests that the etiological bacteria tend to colonize and is hard to eliminate in otitis-prone children.     

Evaluation of Replication of Variants Associated with Genetic Risk of Otitis Media

The first Genome Wide Association Study (GWAS) of otitis media (OM) found evidence of association in the Western Australian Pregnancy Cohort (Raine) study, but lacked replication in an independent OM population. The aim of this study was to investigate association at these loci in our family-based sample of chronic otitis media with effusion and recurrent otitis media (COME/ROM). Autosomal SNPs were selected from the Raine OM GWAS results. SNPs from the Raine cohort GWAS genotyped in our GWAS of COME/ROM had P-values ranging from P = 0.06–0.80. After removal of SNPs previously genotyped in our GWAS of COME/ROM (N = 21) and those that failed Fluidigm assay design (N = 1), 26 SNPs were successfully genotyped in 716 individuals from our COME/ROM family population. None of the SNP associations replicated in our family-based population (unadjusted P = 0.03–0.93). Replication in an independent sample would confirm that these represent novel OM loci, and that further investigation is warranted.