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1.
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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High prevalence of clarithromycin resistance and effect on Helicobacter pylori eradication in a population from Santiago, Chile: cohort study and meta-analysis.
Arenas, A, Serrano, C, Quiñones, L, Harris, P, Sandoval, M, Lavanderos, M, Sepúlveda, R, Maquilón, S, Echeverría, A, Ríos, C, et al
Scientific reports. 2019;(1):20070
Abstract
Helicobacter pylori (H. pylori) eradication using standard triple therapy (STT) with proton pump inhibitors (PPI), amoxicillin and clarithromycin (CLA) has been the standard in Latin America. However, CLA resistance is a rising problem affecting eradication rates. Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication. The primary aims of this study were to evaluate the effect of clarithromycin resistance on H. pylori eradication in a population from Santiago, and to establish the pooled clarithromycin resistance in Santiago, Chile. Symptomatic adult patients attending a tertiary hospital in Santiago were recruited for this study. CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric biopsies, using PCR. The STT was indicated for 14 days and eradication was determined by a urea breath test 4-6 weeks after therapy. A meta-analysis of CLA resistance studies among adult residents in Santiago was performed. Seventy-three out of 121 consecutive patients had positive rapid urease test (RUT) and received STT. Sixty-nine patients (95%) completed the study. The H. pylori eradication rate was 63% and the prevalence of CLA resistance was 26%. According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patients were extensive metabolizers. Multivariable analyses showed that only CLA resistance was significantly and inversely associated with failure of eradication (OR: 0.13; 95% confidence interval [95% CI], 0.04-0.49). A meta-analysis of two previous studies and our sample set (combined n = 194) yielded to a pooled prevalence of CLA resistance of 31.3% (95% CI 23.9-38.7). Our study shows that CLA resistance is associated with failure of H. pylori eradication. Given the high pooled prevalence of CLA resistance, consideration of CLA free therapies in Santiago is warranted. We could recommend bismuth quadruple therapy or high-dose dual therapy, according to bismuth availability. Further studies need to evaluate the best therapy.
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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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Pharmacophore based approach to screen and evaluate novel Mycobacterium cell division inhibitors targeting FtsZ - A modelling and experimental study.
Mitra, K, Chadha, A, Doble, M
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2019;:103-112
Abstract
Tuberculosis, caused by Mycobacterium tuberculosis has been one of the primal afflictions to human, and owing to the current scenario of drug resistance, newer drugs, and alternate targets are required to mitigate the disease. FtsZ is a GTP hydrolyzing protein, conserved in prokaryotes that plays a central role in Z-ring formation during cell division cytokinesis stage. This study employs the use of pharmacophore models derived from two different datasets based on Mtb-FtsZ GTPase inhibition and whole cell antibacterial activity, to virtually screen and shortlist novel compounds from In-house small molecule library as Mtb-FtsZ inhibitors and evaluate their in-vitro and ex-vivo activity. The results revealed Piperine (IC50 = 21.2 ± 0.7 μM), 4-Bromo di-methoxy coumarin (IC50 = 13.0 ± 1.6 μM) and Di-ethyl amino methyl coumarin (IC50 = 19.4 ± 1.1) as potent Mtb-FtsZ GTPase inhibitors which showed considerable antibacterial activity (84.0 ± 2.6 μM, 56.0 ± 4.3 μM and 108 ± 7.1 μM respectively) against M. smegmatis. They appear to be bacteriostatic, as well as treatment with these compounds led to a 3× increase in cell length of M. smegmatis. Further these molecules also altered the FtsZ gene expression by 3-fold when compared to untreated. In addition compound Aloin, an Aloe exudate showed potent Mtb-FtsZ inhibition (IC50 = 16.7 ± 0.4 μM) but exhibited poor anti-mycobacterial activity (>500 μM).
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Helicobacter pylori eradication increases the serum high density lipoprotein cholesterol level in the infected patients with chronic gastritis: A single-center observational study.
Iwai, N, Okuda, T, Oka, K, Hara, T, Inada, Y, Tsuji, T, Komaki, T, Inoue, K, Dohi, O, Konishi, H, et al
PloS one. 2019;(8):e0221349
Abstract
BACKGROUND Extra-gastric manifestation of Helicobacter pylori infection involves systemic inflammation, which results in the production of several cytokines. Only a few clinical trials have investigated the effect of H. pylori eradication therapy on lipid metabolism in the infected patients with chronic gastritis. We aimed to evaluate the effect of H. pylori eradication therapy on lipid metabolism in a Japanese population with chronic gastritis. METHODS One hundred and sixty-three patients with H. pylori-associated chronic gastritis were enrolled in this study between June 2015 and March 2017. They underwent H. pylori eradication therapy; the effects of the therapy were assessed by the urea breath test performed at least 4 weeks after the therapy. After confirming H. pylori eradication, the health screening examination was repeated between May 2016 and August 2018. The clinical parameters were compared before and after the administration of the eradication therapy. RESULTS The mean age of the enrolled patients was 56.7 years, and the mean follow-up duration was 514.7 days. Weight, body mass index, and obesity index were significantly increased post-eradication therapy compared to those pre-eradication therapy. White blood cell and platelet counts were significantly decreased, and high density lipoprotein cholesterol (HDL) level was significantly increased (P = 0.001), while low density lipoprotein cholesterol (LDL), total cholesterol, and triglycerides levels were not altered significantly. Hence, the LDL/HDL ratio was significantly decreased. CONCLUSIONS This study reported that H. pylori eradication therapy increase the HDL levels in the infected patients with chronic gastritis. Hence, the LDL/HDL ratio, which is used to evaluate the risk of atherosclerosis, was significantly decreased post-eradication therapy compared to that pre-eradication therapy.
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Prophylactic Vitamin K Administration in Neonates on Prolonged Antibiotic Therapy: A Randomized Controlled Trial.
Sethi, A, Sankar, MJ, Thukral, A, Saxena, R, Chaurasia, S, Agarwal, R
Indian pediatrics. 2019;(6):463-467
Abstract
OBJECTIVE To compare the prevalence of vitamin K deficiency after intramuscular vitamin K or no treatment in neonates with sepsis on prolonged (>7 days) antibiotic therapy. STUDY DESIGN Open label randomized controlled trial. SETTING Level 3 Neonatal Intensive Care Unit (NICU). PARTICIPANTS Neonates with first episode of sepsis on antibiotics for ≥7 days were included. Neonates with clinical bleeding, vitamin K prior to start of antibiotic therapy (except the birth dose), cholestasis or prenatally diagnosed bleeding disorder were excluded. INTERVENTIONS Randomized to receive 1 mg vitamin K (n=41) or no vitamin K (n=39) on the 7th day of antibiotic therapy. MAIN OUTCOME MEASURES Vitamin K deficiency defined as Protein Induced by Vitamin K Absence (PIVKA-II) >>2 ng/mL after 7 ± 2 days of enrolment. RESULTS The prevalence of vitamin K deficiency was 100% (n=80) at enrolment and it remained 100% even after 7 ± 2 days of enrolment in both the groups. CONCLUSIONS Neonates receiving prolonged antibiotics have universal biochemical vitamin K deficiency despite vitamin K administration on 7th day of antibiotic therapy.
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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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8.
Urinary Tract Infection in Children.
Leung, AKC, Wong, AHC, Leung, AAM, Hon, KL
Recent patents on inflammation & allergy drug discovery. 2019;(1):2-18
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Abstract
BACKGROUND Urinary Tract Infection (UTI) is a common infection in children. Prompt diagnosis and appropriate treatment are very important to reduce the morbidity associated with this condition. OBJECTIVE To provide an update on the evaluation, diagnosis, and treatment of urinary tract infection in children. METHODS A PubMed search was completed in clinical queries using the key terms "urinary tract infection", "pyelonephritis" OR "cystitis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature and the pediatric age group. Patents were searched using the key terms "urinary tract infection" "pyelonephritis" OR "cystitis" from www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com. RESULTS Escherichia coli accounts for 80 to 90% of UTI in children. The symptoms and signs are nonspecific throughout infancy. Unexplained fever is the most common symptom of UTI during the first two years of life. After the second year of life, symptoms and signs of pyelonephritis include fever, chills, rigor, flank pain, and costovertebral angle tenderness. Lower tract symptoms and signs include suprapubic pain, dysuria, urinary frequency, urgency, cloudy urine, malodorous urine, and suprapubic tenderness. A urinalysis and urine culture should be performed when UTI is suspected. In the work-up of children with UTI, physicians must judiciously utilize imaging studies to minimize exposure of children to radiation. While waiting for the culture results, prompt antibiotic therapy is indicated for symptomatic UTI based on clinical findings and positive urinalysis to eradicate the infection and improve clinical outcome. The choice of antibiotics should take into consideration local data on antibiotic resistance patterns. Recent patents related to the management of UTI are discussed. CONCLUSION Currently, a second or third generation cephalosporin and amoxicillin-clavulanate are drugs of choice in the treatment of acute uncomplicated UTI. Parenteral antibiotic therapy is recommended for infants ≤ 2 months and any child who is toxic-looking, hemodynamically unstable, immunocompromised, unable to tolerate oral medication, or not responding to oral medication. A combination of intravenous ampicillin and intravenous/intramuscular gentamycin or a third-generation cephalosporin can be used in those situations. Routine antimicrobial prophylaxis is rarely justified, but continuous antimicrobial prophylaxis should be considered for children with frequent febrile UTI.
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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.