The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study evaluates in vitro antibiotic resistance among Staphylococcus aureus, coagulase-negative staphylococci (CoNS), ...Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae isolates from ocular infections. Here we report resistance rates and trends among conjunctival-sourced ocular isolates collected across the US from 2009 through 2016. A total of 1198 conjunctival isolates (483 S. aureus, 305 CoNS, 208 H. influenzae, 118 S. pneumoniae, and 84 P. aeruginosa) were collected from patients with presumed bacterial conjunctivitis from 57 sites across 40 states. A large proportion of staphylococci demonstrated resistance to oxacillin and azithromycin, while resistance was low against the majority of antibiotics tested for S. pneumoniae, P. aeruginosa, and H. influenzae. Multidrug resistance (≥3 antibiotic classes) was found in 30.2% of S. aureus and 39.0% of CoNS isolates, and methicillin resistance more than doubled the rate of multi-drug resistance (methicillin-resistant S. aureus MRSA, 76.5%; methicillin-resistant CoNS isolates, 72.8%). There was a pattern of increasing mean percent resistance with increasing age by decade of life among S. aureus, MRSA, and CoNS (P≤0.038). Over the eight-year study period, there were small yet significant decreases in resistance rates among S. aureus to azithromycin, ciprofloxacin, tobramycin, trimethoprim, and oxacillin (P≤0.003), and among CoNS and P. aeruginosa (both P<0.05) to ciprofloxacin. These data indicate that antibiotic resistance is high, but did not increase, among conjunctival-sourced isolates collected in the US from 2009 through 2016. For certain antibiotic/pathogen combinations, there was a trend of decreased resistance, including a decrease in oxacillin resistance among S. aureus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this article is to review the evidence for the hypothesis that the core mechanism of dry eye disease (DED) is inflammation, including evidence from recent basic, clinical, and ...translational research involving human patients, animal models, and cell cultures.
Using the key words "dry eye + inflammation," the authors conducted a comprehensive search of the PubMed and Web of Science databases for scientific articles published in English between January 1, 1900 and August 30, 2013 on the role of inflammation in DED in cell cultures, animal models, and humans. The resulting articles were then categorized and reviewed.
The literature search revealed a total of 458 publications, almost all published after 1992. The percentages of original studies and review articles are 77.29% (354) and 22.71% (104), respectively. Among the original studies, the number of reports on human DED is 200 (43.7%), on animal models is 115 (25.1%), and cell cultures is 39 (8.5%). A yearly distributing plot revealed that 76% were published from 2003 to 2011, 53% from 2008 to 2012, and 11% during the first 9 months of 2013. This distribution signifies a rapidly growing awareness of the importance of inflammation in DED pathogenesis.
Inflammation plays a key role in the pathogenesis of DED as evidenced by research using tissue culture, animal models, and subjects with DED. Developing biomarkers for inflammation of the ocular surface will provide improved understanding of the mechanisms leading to DED, classification of the severity of DED, and objective metrics for outcome measures of treatment. The chronicity of the disease suggests that dysregulation of immune mechanisms leads to a cycle of continued inflammation, accompanied by alterations in both innate and adaptive immune responses. Given the underlying mechanism for DED, developing effective and safe anti-inflammatory treatments is likely to be beneficial for patients with DED.
IMPORTANCE: Antibiotic resistance in ocular infections can affect treatment outcomes. Surveillance data on evolving antibacterial susceptibility patterns inform the treatment of such infections. ...OBJECTIVE: To assess overall antibiotic resistance profiles and trends among bacterial isolates from ocular sources collected during 10 years. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of longitudinal data from the ongoing, nationwide, prospective, laboratory-based surveillance study, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study, included clinically relevant isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae cultured from patients with ocular infections at US centers from January 1, 2009, to December 31, 2018. MAIN OUTCOMES AND MEASURES: Minimum inhibitory concentrations were determined for various combinations of antibiotics and species. Odds ratios (ORs) were determined for concurrent antibiotic resistance; analysis of variance and χ2 tests were used to evaluate resistance rates by patient age and geographic region; Cochran-Armitage tests identified changing antibiotic susceptibility trends over time. RESULTS: A total of 6091 isolates (2189 S aureus, 1765 CoNS, 590 S pneumoniae, 767 P aeruginosa, and 780 H influenzae) from 6091 patients were submitted by 88 sites. Overall, 765 S aureus (34.9%) and 871 CoNS (49.3%) isolates were methicillin resistant and more likely to be concurrently resistant to macrolides (azithromycin: S aureus: OR, 18.34 95% CI, 13.64-24.67; CoNS: OR, 4.59 95% CI, 3.72-5.66), fluoroquinolones (ciprofloxacin: S aureus: OR, 22.61 95% CI, 17.96-28.47; CoNS: OR, 9.73 95% CI, 7.63-12.40), and aminoglycosides (tobramycin: S aureus: OR, 18.29 95% CI, 13.21-25.32; CoNS: OR, 6.28 95% CI, 4.61-8.56) compared with methicillin-susceptible isolates (P < .001 for all). Multidrug resistance was observed among methicillin-resistant S aureus (577 75.4%) and CoNS (642 73.7%) isolates. Antibiotic resistance among S pneumoniae isolates was highest for azithromycin (214 36.3%), whereas P aeruginosa and H influenzae isolates showed low resistance overall. Differences in antibiotic resistance were found among isolates by patient age (S aureus: F = 28.07, P < .001; CoNS: F = 11.46, P < .001) and geographic region (S aureus: F = 8.03, P < .001; CoNS: F = 4.79, P = .003; S pneumoniae: F = 8.14, P < .001; P aeruginosa: F = 4.32, P = .005). Small changes in antibiotic resistance were noted over time (≤2.5% per year), with decreases in resistance to oxacillin/methicillin (oxacillin: −2.16%; 95% CI, −3.91% to −0.41%; P < .001) and other antibiotics among S aureus isolates, a decrease in ciprofloxacin resistance among CoNS (−1.38%; 95% CI, −2.24% to −0.52%; P < .001), and an increase in tobramycin resistance among CoNS (0.71%; 95% CI, –0.29% to 1.71%; P = .03). Besifloxacin retained consistently low minimum inhibitory concentrations. CONCLUSIONS AND RELEVANCE: Antibiotic resistance may be prevalent among staphylococcal isolates, particularly among older patients. In this study, a few small differences in antibiotic resistance were observed by geographic region or longitudinally.
The purpose of this study was to assess the quality, reliability, readability, and technical quality of web sites relating to dry eye disease.
A cross-sectional study was conducted that evaluated the ...first 75 web sites on a Google Search by using the keyword "dry eyes." Each web site was evaluated by 2 independent reviewers using the DISCERN, HONcode, and JAMA criteria to assess quality and reliability. Interrater reliability was also analyzed. Readability was assessed using the Flesch-Kincaid readability tests and the Gunning fog, Simple Measure of Gobbledygook, Coleman-Liau, and automated readability indices. Technical quality was determined by the presence of 10 specific features. Web sites were further categorized into institutional (academic centers, medical associations, and government institutions) and private (private practices) categories.
There was no significant difference in scoring observed between the 2 reviewers. The overall mean DISCERN score ± standard error (SE) was 3.2 ± 0.1, the mean HONcode score (±SE) was 9.3 ± 0.3, and the mean JAMA score (±SE) was 1.9 ± 0.1. Institutional web sites had a higher DISCERN score (3.4 ± 0.1 vs. 3.1 ± 0.1; P < 0.05) and HONcode score (10.3 ± 0.5 vs. 8.8 ± 0.4; P < 0.05) than private sites. Technical quality was higher in institutional web sites compared with private web sites ( P < 0.05). Readability was poor among all web sites, with most web sites not achieving below a ninth grade reading level.
Quality, reliability, and readability scores were low for most web sites. Although institutional web sites achieved higher scores than private web sites, revision is warranted to improve their overall quality of information and readability profile.
This study is to identify subgroups of DED patients with different tear cytokine profiles and compare their DED symptoms and signs among subgroups. Baseline tear cytokines (IL-1β, IL-6, IL-8, IL-10, ...IL-17A, IFN-γ and TNF-α) were measured using a magnetic bead assay. DED symptoms were assessed by Ocular Surface Disease Index (OSDI) and signs were assessed by corneal and conjunctival staining, tear break-up time (TBUT), Schirmer's test, tear osmolarity and meibomian gland dysfunction (MGD). Latent profile analysis was performed to identify subgroups, and their scores of DED symptoms and signs were compared using generalized linear regression. Among 131 patients with total tear volume > 4 µl from both eyes, subgroup 1 (n = 23) significantly higher in IL-6 and IL-8 (all p < 0.001) and subgroup 2 (n = 108) significantly higher in IL-10 (p = 0.03), IL-17A (p < 0.001), and IFN-γ (p < 0.001). Both subgroups were similar in demographics and DED symptoms, but subgroup 1 had significantly more severe DED signs: higher conjunctival staining (3.38 vs. 2.69, p = 0.04), corneal staining (4.26 vs. 3.03, p = 0.03), lower Schirmer's test score (8.20 vs. 13.72, p < 0.001), and higher composite severity score of DED sign (0.62 vs. 0.45, p = 0.002). We identified two DED subgroups with different profiles of tear cytokines. Patients in these subgroups differed significantly in DED signs, supporting the inflammation's role in DED development and progression.
Biomarkers with minimally invasive and reproducible objective metrics provide the key to future paradigm shifts in understanding of the underlying causes of dry eye disease (DED) and approaches to ...treatment of DED. We review biomarkers and their validity in providing objective metrics for DED clinical research and patient care.
The English-language literature in PubMed primarily over the last decade was surveyed for studies related to identification of biomarkers of DED: (1) inflammation, (2) point-of-care, (3) ocular imaging, and (4) genetics. Relevant studies in each group were individually evaluated for (1) methodological and analytical details, (2) data and concordance with other similar studies, and (3) potential to serve as validated biomarkers with objective metrics.
Significant work has been done to identify biomarkers for DED clinical trials and for patient care. Interstudy variation among studies dealing with the same biomarker type was high. This could be attributed to biologic variations and/or differences in processing, and data analysis. Correlation with other signs and symptoms of DED was not always clear or present.
Many of the biomarkers reviewed show the potential to serve as validated and objective metrics for clinical research and patient care in DED. Interstudy variation for a given biomarker emphasizes the need for detailed reporting of study methodology, including information on subject characteristics, quality control, processing, and analysis methods to optimize development of nonsubjective metrics. Biomarker development offers a rich opportunity to significantly move forward clinical research and patient care in DED.
DED is an unmet medical need - a chronic pain syndrome associated with variable vision that affects quality of life, is common with advancing age, interferes with the comfortable use of contact lenses, and can diminish results of eye surgeries, such as cataract extraction, LASIK, and glaucoma procedures. It is a worldwide medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.
PURPOSE:To determine the levels of 8 important cytokines and 1 chemokine in tears of patients with dry eye disease.
METHODS:Tear samples were collected from 7 patients with dry eye disease and 7 ...healthy volunteers, and impression cytology samples were collected from 3 of the dry eye patients and 3 of the normal controls. Tears were analyzed for the presence of 8 cytokines interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-1β and 1 chemokine (IL-8). The cytokines and chemokine in each tear sample were measured using Invitrogenʼs Multiplex Bead Immunoassays. The impression cytology samples were analyzed for IL-1β, IL-6, IL-8, and TNF-α mRNA expression using real-time reverse transcriptase polymerase chain reaction anlaysis.
RESULTS:All cytokines and the chemokine measured were significantly increased in the tears of dry eye patients as compared to normal controls. mRNA of all four markers was increased, and the fold increase correlated well with the fold increase of the cytokine concentration found in the tear samples.
CONCLUSION:Tears from dry eye patients contain significantly increased concentrations of cytokines that show correlation to severity of the disease. The upregulation of their respective genes in the conjunctiva suggests that the concentration increase is not the result of evaporative effects, but of overproduction. These findings suggest that cytokines may play an important role in dry eye disease and topical cytokine modulators may be explored as a therapeutic approach to dry eye disease.
PURPOSE:To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED).
METHODS:This is a prospective, ...observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine).
RESULTS:The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47–0.67) and with measures of interference with activities of daily living general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39–0.65).
CONCLUSIONS:Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.
PDF
