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Small Intestinal Bacterial Overgrowth: Clinical Features and Therapeutic Management.
Rao, SSC, Bhagatwala, J
Clinical and translational gastroenterology. 2019;(10):e00078
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Abstract
Small intestinal bacterial overgrowth (SIBO) is a common, yet underrecognized, problem. Its prevalence is unknown because SIBO requires diagnostic testing. Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the "best diagnostic method," but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.
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The use of antibiotics and risk of kidney stones.
Joshi, S, Goldfarb, DS
Current opinion in nephrology and hypertension. 2019;(4):311-315
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Abstract
PURPOSE OF REVIEW The effect of the intestinal microbiome on urine chemistry and lithogenicity has been a popular topic. Here we review the evidence for exposure to antibiotics increasing the risk of nephrolithiasis. RECENT FINDINGS Studies of the intestinal microbiome have focused on Oxalobacter formigenes, an anaerobe that frequently colonizes the human colon. As a degrader of fecal oxalate its presence is associated with lower urinary oxalate, which would be protective against calcium oxalate stone formation. It also appears capable of stimulating colonic oxalate secretion. A recent study showed that antibiotics can eliminate colonization with O. formigenes. In a case-control study, exposure to sulfa drugs, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine, and broad spectrum penicillins prospectively increased the odds of nephrolithiasis. The effect was greatest for those exposed at younger ages and 3-6 months before being diagnosed with nephrolithiasis. SUMMARY Recent evidence suggests a possible, causal role of antibiotics in the development of kidney stones. A possible explanation for this finding includes alterations in the microbiome, especially effects on oxalate-degrading bacteria like O. formigenes. Ample reasons to encourage antibiotic stewardship already exist, but the possible role of antibiotic exposure in contributing to the increasing prevalence of kidney stones in children and adults is another rationale.
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Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments.
Barbieri, JS, Spaccarelli, N, Margolis, DJ, James, WD
Journal of the American Academy of Dermatology. 2019;(2):538-549
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Abstract
Acne is one of the most common diseases worldwide and affects ∼50 million individuals in the United States. Oral antibiotics are the most common systemic agent prescribed for the treatment of acne. However, their use might be associated with a variety of adverse outcomes including bacterial resistance and disruption of the microbiome. As a result, multiple treatment guidelines call for limiting the use of oral antibiotics in the treatment of acne, although actual prescribing often does not follow these guidelines. In this review, the rationale for concerns regarding the use of oral antibiotics for the management of acne is reviewed. In addition, we will discuss our approach to complying with the intent of the guidelines, with a focus on novel topical agents, dietary modification, laser and light-based modalities, and systemic medications, such as spironolactone, combined oral contraceptives, and oral isotretinoin.
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Prevention of Clostridium difficile Infection in Critically Ill Adults.
Leedahl, DD, Personett, HA, Nagpal, A, Barreto, EF
Pharmacotherapy. 2019;(3):399-407
Abstract
The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policymakers.
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Non-antibiotic therapy for Clostridioides difficile infection: a review.
Yang, J, Yang, H
Critical reviews in clinical laboratory sciences. 2019;(7):493-509
Abstract
Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.
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Multi-level regulation of coelimycin synthesis in Streptomyces coelicolor A3(2).
Bednarz, B, Kotowska, M, Pawlik, KJ
Applied microbiology and biotechnology. 2019;(16):6423-6434
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Abstract
Despite being a yellow pigment visible to the human eye, coelimycin (CPK) remained to be an undiscovered secondary metabolite for over 50 years of Streptomyces research. Although the function of this polyketide is still unclear, we now know that its "cryptic" nature is attributed to a very complex and precise mechanism of cpk gene cluster regulation in the model actinomycete S. coelicolor A3(2). It responds to the stringent culture density and timing of the transition phase by the quorum-sensing butanolide system and to the specific nutrient availability/uptake signals mediated by the global (pleiotropic) regulators; many of which are two-component signal transduction systems. The final effectors of this regulation cascade are predicted to be two cluster-situated Streptomyces antibiotic regulatory proteins (SARPs) putatively activating the expression of type I polyketide synthase (PKS I) genes. After its synthesis, unstable, colorless antibiotic coelimycin A reacts with specific compounds in the medium losing its antibacterial properties and giving rise to yellow coelimycins P1 and P2. Here we review the current knowledge on coelimycin synthesis regulation in Streptomyces coelicolor A3(2). We focus on the regulatory feedback loop which interconnects the butanolide system with other cpk cluster-situated regulators. We also present the effects exerted on cpk genes expression by the global, pleiotropic regulators, and the regulatory connections between cpk and other biosynthetic gene clusters.
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Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters.
Rudenko, N, Golovchenko, M, Kybicova, K, Vancova, M
Parasites & vectors. 2019;(1):237
Abstract
The survival of spirochetes from the Borrelia burgdorferi (sensu lato) complex in a hostile environment is achieved by the regulation of differential gene expression in response to changes in temperature, salts, nutrient content, acidity fluctuation, multiple host or vector dependent factors, and leads to the formation of dormant subpopulations of cells. From the other side, alterations in the level of gene expression in response to antibiotic pressure leads to the establishment of a persisters subpopulation. Both subpopulations represent the cells in different physiological states. "Dormancy" and "persistence" do share some similarities, e.g. both represent cells with low metabolic activity that can exist for extended periods without replication, both constitute populations with different gene expression profiles and both differ significantly from replicating forms of spirochetes. Persisters are elusive, present in low numbers, morphologically heterogeneous, multi-drug-tolerant cells that can change with the environment. The definition of "persisters" substituted the originally-used term "survivors", referring to the small bacterial population of Staphylococcus that survived killing by penicillin. The phenomenon of persisters is present in almost all bacterial species; however, the reasons why Borrelia persisters form are poorly understood. Persisters can adopt varying sizes and shapes, changing from well-known forms to altered morphologies. They are capable of forming round bodies, L-form bacteria, microcolonies or biofilms-like aggregates, which remarkably change the response of Borrelia to hostile environments. Persisters remain viable despite aggressive antibiotic challenge and are able to reversibly convert into motile forms in a favorable growth environment. Persisters are present in significant numbers in biofilms, which has led to the explanation of biofilm tolerance to antibiotics. Considering that biofilms are associated with numerous chronic diseases through their resilient presence in the human body, it is not surprising that interest in persisting cells has consequently accelerated. Certain diseases caused by pathogenic bacteria (e.g. tuberculosis, syphilis or leprosy) are commonly chronic in nature and often recur despite antibiotic treatment. Three decades of basic and clinical research have not yet provided a definite answer to the question: is there a connection between persisting spirochetes and recurrence of Lyme disease in patients?
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Challenges and opportunities related to the use of chitosan as a food preservative.
Hu, Z, Gänzle, MG
Journal of applied microbiology. 2019;(5):1318-1331
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Abstract
Chitosan has attracted a growing attention as a food preservative due to its versatility, nontoxicity, biodegradability and biocompatibility. This review aims to provide a critical appraisal of the limitations and opportunities of the use of chitosan as a food preservative. The application of chitosan as a food preservative necessitates insights into mechanisms of chitosan-mediated cell death and injury, factors affecting chitosan activity and effects of chitosan on food safety and quality. Chitosan exerts antimicrobial activity by perturbing the negatively charged cell envelope of micro-organisms with its polycationic structure. Intrinsic characteristics, including molecular weight and degree of deacetylation (DD), and other ambient conditions, including pH, temperature and neighbouring components, affect chitosan activity. Because the antimicrobial activity of chitosan is mainly based on ionic interactions with negatively charged components of the bacterial cell envelope, the food matrix can strongly interfere with the antimicrobial activity of chitosan. Despite its limited antimicrobial efficacy, chitosan demonstrates both bactericidal and bacteriostatic effects in specific food products. Moreover, chitosan can also enhance the efficacy of commercial intervention technologies, such as heat and pressure treatment, and aid the preservation of food quality, including retardation of lipid oxidation, weight loss and deterioration in sensory attributes.
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New Nutritional and Therapeutical Strategies of NEC.
Teresa, C, Antonella, D, de Ville de Goyet Jean,
Current pediatric reviews. 2019;(2):92-105
Abstract
Necrotizing enterocolitis (NEC) is an acquired severe disease of the digestive system affecting mostly premature babies, possibly fatal and frequently associated to systemic complications. Because of the severity of this condition and the possible long-term consequences on the child's development, many studies have aimed at preventing the occurrence of the primary events at the level of the bowel wall (ischemia and necrosis followed by sepsis) by modifying or manipulating the diet (breast milk versus formula) and/or the feeding pattern (time for initiation after birth, continuous versus bolus feeding, modulation of intake according clinical events). Feeding have been investigated so far in order to prevent NEC. However, currently well-established and shared clinical nutritional practices are not available in preventing NEC. Nutritional and surgical treatments of NEC are instead well defined. In selected cases surgery is a therapeutic option of NEC, requiring sometimes partial intestinal resection responsible for short bowel syndrome. In this paper we will investigate the available options for treating NEC according to the Walsh and Kliegman classification, focusing on feeding practices in managing short bowel syndrome that can complicate NEC. We will also analyze the proposed ways of preventing NEC.
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Association between exposure to macrolides and the development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.
Abdellatif, M, Ghozy, S, Kamel, MG, Elawady, SS, Ghorab, MME, Attia, AW, Le Huyen, TT, Duy, DTV, Hirayama, K, Huy, NT
European journal of pediatrics. 2019;(3):301-314
Abstract
Macrolides are bacteriostatic antibiotics with a broad spectrum of activity against Gram-positive bacteria. The aim of this study was to systematically review and meta-analyze the association between infantile hypertrophic pyloric stenosis (IHPS) and macrolides. Nine databases were searched systematically for studies with information on the association between macrolides and IHPS. We combined findings using random effects models. Our study revealed 18 articles investigating the association between macrolides and IHPS. There was a significant association between the development of IHPS and erythromycin (2.38, 1.06-5.39). The association was strong when erythromycin was used during the first 2 weeks of life (8.14, 4.29-15.45). During breastfeeding, use of macrolides showed no significant association with IHPS in infants (0.96, 0.61-1.53). IHPS was not associated with erythromycin (1.11, 0.9-1.36) or macrolides use during pregnancy (1.15, 0.98-1.36).Conclusions: There is an association between erythromycin use during infancy and developing IHPS in infants. However, no significant association was found between macrolides use during pregnancy or breastfeeding. Additional large studies are needed to further evaluate potential association with macrolide use. What is known? • Erythromycin intake in the first 2 weeks of life is associated with an increased risk of pyloric stenosis. What is New? • There is currently no evidence of significant association between macrolides use during pregnancy or breastfeeding and pyloric stenosis.