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1.
High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.
Matho, A, Mulqueen, M, Tanino, M, Quidort, A, Cheung, J, Pollard, J, Rodriguez, J, Swamy, S, Tayler, B, Garrison, G, et al
PloS one. 2018;(5):e0196734
Abstract
BACKGROUND The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit. OBJECTIVE To see if a higher dose of amoxicillin will lead to more rapid improvement. DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines. INTERVENTIONS Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR). MAIN MEASURE The primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment. KEY RESULTS Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048). CONCLUSIONS Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02340000.
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2.
Role of divalent metals in infectious disease susceptibility and outcome.
Weiss, G, Carver, PL
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2018;(1):16-23
Abstract
BACKGROUND Divalent metals play important roles in maintaining metabolism and cellular growth of both eukaryotic hosts and invading microbes. Both metal deficiency and overload can result in abnormal cellular function or damage. Given its central role in host-pathogen interactions, subtle alterations of divalent metal homeostasis can occur in the course of infectious diseases which aim, from the host perspective, either to reduce the availability of respective metals to microbes or to use toxic metal accumulation to eliminate pathogens. AIMS To provide the reader with background information and clinical data on divalent metal homeostasis in host-pathogen interactions, how this affects the course of infectious disease and whether correction of metal disturbances has shown benefit in infections. SOURCES An in-depth analysis of PubMed articles related to the topic of this review published in English between 1970 and 2016 was performed. CONTENT From the microbial perspective, divalent metals are essential for growth and pathogenicity and to mount effective protection against antimicrobial host responses, including toxic radical formation. Microbes have evolved multiple strategies to control their access to divalent metals. From the clinical perspective, alterations of divalent metal levels may result in increased or decreased susceptibility to infection and often occur in response to infections. However, keeping in mind the strategies underlying such alterations, for which the term 'nutritional immunity' was coined, the uncritical correction of such divalent metal imbalances may cause harm to patients. This review addresses the role of the divalent metals iron, selenium, zinc, manganese and copper in infectious diseases from a mechanistic and clinical perspective. IMPLICATIONS We point out areas of research needed to expand our limited knowledge, hoping to improve the clinical management of patients with infections and to identify promising new targets for treatment by modulation of host or microbe divalent metal metabolism.
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3.
Bioactivities of Phenolics by Focusing on Suppression of Chronic Diseases: A Review.
Shahidi, F, Yeo, J
International journal of molecular sciences. 2018;(6)
Abstract
Phenolics, which are secondary metabolites of plants, exhibit remarkable bioactivities. In this contribution, we have focused on their protective effect against chronic diseases rather than their antioxidant activities, which have been widely discussed in the literature. A large body of epidemiological studies has proven the bioactivities of phenolics in both standard compounds and natural extracts: namely, anticancer, anti-inflammatory, and antibacterial activities as well as reducing diabetes, cardiovascular disease, and neurodegenerative disease. Phenolics also display anti-analgesic, anti-allergic, and anti-Alzheimer's properties. Thus, this review provides crucial information for better understanding the bioactivities of phenolics in foods and fills a gap in the existing collective and overall knowledge in the field.
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4.
Nanocoatings for Chronic Wound Repair-Modulation of Microbial Colonization and Biofilm Formation.
Mihai, MM, Preda, M, Lungu, I, Gestal, MC, Popa, MI, Holban, AM
International journal of molecular sciences. 2018;(4)
Abstract
Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches.
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5.
Probiotics in Prevention of Surgical Site Infections.
Siddharthan, R, Chapek, M, Warren, M, Martindale, R
Surgical infections. 2018;(8):781-784
Abstract
Despite significant improvements in peri-operative care, surgical site infections (SSIs) remain an important contributor to morbidity, cost, and death. The human gastrointestinal tract is a complex microenvironment linking host cells and the indigenous microflora or "microbiome," creating a "super-organism" that engages in macro-nutrient and micro-nutrient extraction for the host while serving as a barrier to toxins and other detrimental bacterial end-products. Maintaining a healthy microbiome in the peri-operative period may enable control of multi-drug resistance (MDR) organisms, whereas use of antibiotics simply resets the dysbiotic relation by eliminating multiple strains of bacteria. Such loss of microbial diversity or abundance can slow wound healing. Use of pro-biotics to prevent infection has been evaluated in several studies, but their utility is not yet clear. There is a clear need for randomized trials to draw firm conclusions about their efficacy and to make clinical recommendations.
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6.
Vitamin D-binding protein in cervicovaginal fluid as a non-invasive predictor of intra-amniotic infection and impending preterm delivery in women with preterm labor or preterm premature rupture of membranes.
Kook, SY, Park, KH, Jang, JA, Kim, YM, Park, H, Jeon, SJ
PloS one. 2018;(6):e0198842
Abstract
OBJECTIVE To determine whether vitamin D-binding protein (VDBP) in cervicovaginal fluid (CVF) is independently predictive of intra-amniotic infection and imminent spontaneous preterm delivery (SPTD, delivery within 48 hours) in women with preterm labor with intact membranes (PTL) or preterm premature rupture of membranes (PPROM). METHOD This was a single-center retrospective cohort study. CVF samples for VDBP assays were obtained along with serum C-reactive protein (CRP) levels immediately after amniocentesis in consecutive women with PTL (n = 148) or PPROM (n = 103) between 23.0 and 34.0 weeks of gestation. VDBP levels in CVF were determined by enzyme-linked immunosorbent assay kits. The primary outcome measures were intra-amniotic infection [defined as positive amniotic fluid (AF) culture] and SPTD within 48 hours after sampling. RESULTS In the multivariable analysis, elevated VDBP levels in CVF samples of PTL women were significantly associated with intra-amniotic infection and imminent preterm delivery, even after adjusting for potential confounders (e.g., gestational age at sampling, parity, and serum CRP). However, these relationships were not found in women with PPROM. In women with PTL, the areas under receiver operating characteristic curves of CVF VDBP level for predicting intra-amniotic infection and imminent preterm delivery were 0.66 and 0.71, with cut-off values of 1.76 μg/mL (sensitivity of 64.3% and specificity of 78.4%) and 1.37 μg/mL (sensitivity of 65.4% and specificity of 72.6%), respectively. The CVF VDBP levels were significantly higher in women with PPROM than in those with PTL. CONCLUSIONS VDBP in the CVF independently predicts intra-amniotic infection and imminent preterm delivery in women with PTL, whereas in women with PPROM, an elevated VDBP level in CVF is not associated with increased risks of these two outcome variables.
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Body mass index and the risk of infection - from underweight to obesity.
Dobner, J, Kaser, S
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2018;(1):24-28
Abstract
BACKGROUND Nutritional status is a well-known risk factor for metabolic and endocrine disorders. Recent studies suggest that dietary intake also affects immune function and as a consequence infection risk. AIMS This reviews aims to give an overview on the effect of body weight on infection rate at different periods of life. SOURCES Clinically relevant prospective, cross-sectional and case-control community-based studies are summarized. CONTENT In children and adolescents underweight is a significant risk factor for infection especially in developing countries, probably reflecting malnutrition and poor hygienic standards. Data from industrialized countries suggest that infection rate is also increased in obese children and adolescents. Similarly, several studies suggest a U-shaped increased infection rate in both underweight and obese adults. In the latter, infections of the skin and respiratory tract as well as surgical-site infections have consistently been reported to be more common than in normal-weight participants. Paradoxically, mortality of critically ill patients was reduced in obesity in some studies. IMPLICATIONS Several studies in children or adults suggest that both underweight and obesity are associated with increased infection risk. However, confounding factors such as malnutrition, hygienic status and underlying disease or co-morbidities might aggravate accurate assessment of the impact of body weight on infection risk.
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8.
Metal homeostasis in infectious disease: recent advances in bacterial metallophores and the human metal-withholding response.
Neumann, W, Gulati, A, Nolan, EM
Current opinion in chemical biology. 2017;:10-18
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Abstract
A tug-of-war between the mammalian host and bacterial pathogen for nutrients, including first-row transition metals (e.g. Mn, Fe, Zn), occurs during infection. Here we present recent advances about three metal-chelating metabolites that bacterial pathogens deploy when invading the host: staphylopine, staphyloferrin B, and enterobactin. These highlights provide new insights into the mechanisms of bacterial metal acquisition and regulation, as well as the contributions of host-defense proteins during the human innate immune response. The studies also underscore that the chemical composition of the microenvironment at an infection site can influence bacterial pathogenesis and the innate immune system.
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Perioperative infections in congenital heart disease.
Murni, IK, MacLaren, G, Morrow, D, Iyer, P, Duke, T
Cardiology in the young. 2017;(S6):S14-S21
Abstract
BACKGROUND Perioperative infections have significant consequences for children with congenital heart disease (CHD), which can manifest as acute or chronic infection followed by poor growth and progressive cardiac failure. The consequences include delayed or higher-risk surgery, and increased postoperative morbidity and mortality. METHODS A systematic search for studies evaluating the burden and interventions to reduce perioperative infections in children with CHD was undertaken using PubMed. RESULTS Limited studies conducted in low- to middle-income countries demonstrated the large burden of perioperative infections among children with CHD. Most studies focussed on infections after surgery. Few studies evaluated strategies to prevent preoperative infection or the impact of infection on decision-making around the timing of surgery. Children with CHD have multiple risk factors for infections including delayed presentation, inadequate treatment of cardiac failure, and poor nutrition. CONCLUSIONS The burden of perioperative infections is high among children with CHD, and studies evaluating the effectiveness of interventions to reduce these infections are lacking. As good nutrition, early corrective surgery, and measures to reduce nosocomial infection are likely to play a role, practical steps can be taken to make surgery safer.
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Macrolide and fluoroquinolone mediated cardiac arrhythmias: clinical considerations and comprehensive review.
Cornett, E, Novitch, MB, Kaye, AD, Pann, CA, Bangalore, HS, Allred, G, Bral, M, Jhita, PK, Kaye, AM
Postgraduate medicine. 2017;(7):715-724
Abstract
While there is evidence for cardiac arrhythmias associated with macrolide and fluoroquinolone antibiotics, there is still debate among health care providers as to whether this risk of arrhythmia is overstated. A joint panel of the US Food and Drug Administration suggested that macrolide and fluoroquinolone labels need much stronger warnings regarding the possible serious adverse cardiac effects associated with these antibiotics, especially since they are so widely prescribed. And while health care providers may differ on the pertinence of the cardiac risks associated with antibiotic use, they can undoubtedly minimize the cardiac effects that are associated with these antibiotics by paying attention to the cardiac risk factors and drug history associated with the patient. Relevant studies for our review were identified from a PubMed search using keywords and combined word searches involving macrolides, fluoroquinolones, and cardiac arrhythmias. We attempted to include as many recent (>2015) articles as possible. We included case reports, randomized, controlled trials, observational studies, case-control studies, systematic reviews, and retrospective studies. Underlying cardiac issues can predispose patients to harmful cardiac side effects that can be exacerbated in the presence of antibiotics. The health care provider should rule out any risk factor associated with antibiotic-induced cardiac arrhythmia in the event that a patient does need a macrolide or fluoroquinolone antibiotic. Rigorous patient evaluation and a detailed patient history, including short and long term medication use, is the likely key to reducing any risk of cardiac arrhythmias associated with macrolides and fluoroquinolones. Clinicians should be cautious when prescribing macrolide and fluoroquinolone medications to patients with risk factors that may lead to antibiotic-induced cardiac arrhythmias, including a slow heart rate and those that are taking medications to treat arrhythmias.