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1901. A large-scale whole-genome comparison shows that experimental evolution in response to antibiotics predicts changes in naturally evolved clinical <i>Pseudomonas aeruginosa</i>. Full Text available with Trip Pro

A large-scale whole-genome comparison shows that experimental evolution in response to antibiotics predicts changes in naturally evolved clinical Pseudomonas aeruginosa. Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have mutations that make them antibiotic resistant, making treatment difficult. To identify resistance-associated mutations we experimentally evolved the antibiotic sensitive (...) strain P. aeruginosa PAO1 to become resistant to three widely used anti-pseudomonal antibiotics, ciprofloxacin, meropenem and tobramycin. Mutants could tolerate up to 2048-fold higher concentrations of antibiotic than strain PAO1. Genome sequences were determined for thirteen mutants for each antibiotic. Each mutant had between 2 and 8 mutations. For each antibiotic at least 8 genes were mutated in multiple mutants, demonstrating the genetic complexity of resistance. For all three antibiotics

2019 Antimicrobial Agents and Chemotherapy

1902. HAMLET, a protein complex from human milk has bactericidal activity and enhances the activity of antibiotics against pathogenic <i>Streptococci</i>. Full Text available with Trip Pro

HAMLET, a protein complex from human milk has bactericidal activity and enhances the activity of antibiotics against pathogenic Streptococci. HAMLET is a protein-lipid complex derived from human milk that was first described for its tumoricidal activity. Later studies showed that HAMLET also has direct bactericidal activity against select species of bacteria, with highest activity against Streptococcus pneumoniae Additionally, HAMLET in combination with various antimicrobial agents can (...) make a broader range of antibiotic-resistant bacterial species sensitive to antibiotics. Here, we show that HAMLET has direct antibacterial activity not only against pneumococci, but also against Streptococcus pyogenes (GAS) and Streptococcus agalactiae (GBS). Analogous to pneumococci, HAMLET-treatment of GAS and GBS resulted in depolarization of the bacterial membrane followed by membrane permeabilization and death that could be inhibited by calcium and sodium transport inhibitors. Treatment

2019 Antimicrobial Agents and Chemotherapy

1903. Estimating the size of the United States market for new antibiotics with activity against carbapenem-resistant Enterobacteriaceae. Full Text available with Trip Pro

Estimating the size of the United States market for new antibiotics with activity against carbapenem-resistant Enterobacteriaceae. New antibiotics with activity against carbapenem-resistant Enterobacteriaceae (CRE) improve outcomes of CRE-infected patients. However, companies developing these drugs have faced financial difficulties. Sales of ceftazidime-avibactam, meropenem-vaborbactam and plazomicin in the United States (US) totaled $101 million from February 2018-January 2019. We estimate (...) the current annual US market for new anti-CRE antibiotics is $289 million (range: $169-$439 million). Without new antibiotic development models and/or reimbursement reform, the majority of anti-CRE drugs will be commercially inviable.Copyright © 2019 American Society for Microbiology.

2019 Antimicrobial Agents and Chemotherapy

1904. Comparative <i>In Vivo</i> Antibacterial Activity of Human-Simulated Exposures of Cefiderocol and Ceftazidime against <i>Stenotrophomonas maltophilia</i> in the Murine Thigh Model. Full Text available with Trip Pro

Comparative In Vivo Antibacterial Activity of Human-Simulated Exposures of Cefiderocol and Ceftazidime against Stenotrophomonas maltophilia in the Murine Thigh Model. Cefiderocol is a novel siderophore cephalosporin that utilizes bacterial ferric iron transports to cross the outer membrane. Cefiderocol shows high stability against all classes of β-lactamases, rendering it extremely potent against carbapenem- and multidrug-resistant Gram-negative organisms. Using a neutropenic

2019 Antimicrobial Agents and Chemotherapy

1905. Antibiotic prophylaxis with high-dose cefoxitin in bariatric surgery: an observational prospective single center study. Full Text available with Trip Pro

Antibiotic prophylaxis with high-dose cefoxitin in bariatric surgery: an observational prospective single center study. The optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-gram dosing regimen of cefoxitin against the most frequent pathogens that infect patients undergoing bariatric surgery.This observational prospective study included obese patients who required bariatric surgery and a 4-gram dose of cefoxitin (...) as an antibiotic prophylaxis. Serum concentrations were measured during surgery (incision, wound closure and in case of reinjection). The pharmacokinetic/pharmacodynamic (PK/PD) target was to obtain free cefoxitin concentrations above 4× MIC, from incision to wound closure (100% ƒT>4xMIC). The targeted MIC was based on the worst-case scenario (the highest ECOFF value of Staphylococcus aureus, Enterobacteriaceae and anaerobic bacteria). The secondary outcomes were the factors related to underdosage.Two hundred

2019 Antimicrobial Agents and Chemotherapy

1906. Antibiotic modulation of mucins in otitis media; should this change our approach to watchful waiting? Full Text available with Trip Pro

Antibiotic modulation of mucins in otitis media; should this change our approach to watchful waiting? Gel-forming mucins (GFMs) play important roles in otitis media (OM) pathogenesis. Increased mucin expression is activated by pathogens and proinflammatory cytokines. Bacterial biofilms influence inflammation and resolution of OM and may contribute to prolonged mucin production. The influence of specific pathogens on mucin expression and development of chronic OM with effusion (OME) remains (...) an area of significant knowledge deficit.To assess the relationship between GFM expression, specific pathogens, middle ear mucosal (MEM) changes, biofilm formation, and antibiotic utilization.Mixed gender chinchillas were inoculated with nontypeable Haemophilus influenzae (NTHi) strain 86028NP or Streptococcus pneumoniae (SP) strain TIGR4 via transbulla injection. Antibiotic was administered on day 3-5 post inoculation. GFM expression was measured by quantitative PCR. Biofilm formation was identified

2019 International Journal of Pediatric Otorhinolaryngology

1907. The impact of continuity of care on antibiotic prescribing in acute otitis media. (Abstract)

The impact of continuity of care on antibiotic prescribing in acute otitis media. The rate of antibiotic prescribing for acute otitis media (AOM) remains high despite efforts to decrease inappropriate use. Studies have aimed to understand the prescribing patterns of providers to increase antibiotic stewardship. Watch and wait (WAW) prescriptions are effective at decreasing the number of antibiotic prescriptions being filled by patients. Additionally, poor continuity of care has been associated (...) with higher cost and lower quality health care.To understand the antibiotic prescribing habits for AOM in a largely Hispanic population.A retrospective review was performed from 2016 to 2018 of all patients under 25 years old with a diagnosis of AOM seen at multiple outpatient primary care clinics of a single institution. Charts were reviewed for factors including race, ethnicity, gender, insurance status, presence of fever, primary care physician visit, and treatment choice. Data were collected

2019 International Journal of Pediatric Otorhinolaryngology

1908. Prophylactic antibiotics in head and neck free flap surgery: A novel protocol put to the test. (Abstract)

Prophylactic antibiotics in head and neck free flap surgery: A novel protocol put to the test. Recent evidence supports the use of ampicillin-sulbactam as a favored choice for antibiotic prophylaxis following head and neck free flap reconstructive surgery. However, there is a paucity of evidence guiding the optimal duration of antibiotic prophylaxis. The aim of this study is to compare the infection rates of short courses of ampicillin-sulbactam versus extended courses of various antibiotics (...) in head and neck free flap reconstructive surgery.This is a retrospective cohort study conducted from 2012 to 2017 at a tertiary academic center on 266 consecutive patients undergoing head and neck surgery with free flap reconstruction. The primary outcome measure was the rate of any infection within 30 days of surgery.There were 149 patients who received antibiotic prophylaxis for an extended duration of at least seven days. 117 patients received a short course of antibiotics defined as 24 h for non

2019 American Journal of Otolaryngology

1909. Intranasal Septal Splints: Prophylactic Antibiotics and Nasal Microbiology. (Abstract)

Intranasal Septal Splints: Prophylactic Antibiotics and Nasal Microbiology. Intranasal septal splints are often used in nasal septal surgeries. Routine use of postoperative antibiotics is an accepted practice, although data regarding its efficacy in preventing postsurgical complications are limited. This study aimed to examine bacterial colonization on septal splints following prophylactic antibiotic therapy and the association with postoperative infections.Fifty-five patients underwent (...) septoplasty by a single surgeon between March 2015 and April 2016. All had intranasal septal splints and were given antibiotic prophylaxis for 7 days until removal of splints. Nasal cultures were taken before surgery, and septal splints were examined for bacterial colonization following their removal.Thirty-six patients (65%) had positive nasal culture prior to surgery. The most common isolates were Staphylococcus aureus (30%) and Enterobacteriaceae species (66%). All these patients had postoperative

2019 Rhinology and Laryngology

1910. LC-ESI-MS/MS Phenolic Profile of <i>Volutaria lippii</i> (L.) Cass. Extracts and Evaluation of Their <i>In Vitro</i> Antioxidant, Antiacetylcholinesterase, Antidiabetic, and Antibacterial Activities. Full Text available with Trip Pro

LC-ESI-MS/MS Phenolic Profile of Volutaria lippii (L.) Cass. Extracts and Evaluation of Their In Vitro Antioxidant, Antiacetylcholinesterase, Antidiabetic, and Antibacterial Activities. Volutaria lippii (L.) Cass., an indigenous perennial herb from the Tunisian flora, belongs to the medicinally important genus Volutaria Cass. (Asteraceae) which comprises eighteen species widely distributed in the Irano-Turanian and Mediterranean Basin. In this study, five different extracts from (...) Tunisian Volutaria lippii (L.) Cass. were evaluated for their in vitro antioxidant, antiacetylcholinesterase, antidiabetic, and antibacterial activities as well as for their total phenolic and flavonoid contents. The results indicated that the ethyl acetate and aqueous fractions have the highest levels in phenolic and flavonoid contents and showed remarkable antioxidant activities using DPPH (IC50= 11.50±0.57 and 28.81±1.35μg/mL, respectively), total antioxidant capacity (105.21±0.01 and 98.77±0.02 mg

2019 Evidence-based Complementary and Alternative Medicine (eCAM)

1911. Comparison of the Antibacterial Efficacy of <i>Commiphora molmol</i> and Sodium Hypochlorite as Root Canal Irrigants against <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i>. Full Text available with Trip Pro

Comparison of the Antibacterial Efficacy of Commiphora molmol and Sodium Hypochlorite as Root Canal Irrigants against Enterococcus faecalis and Fusobacterium nucleatum. The investigation aims to compare antimicrobial efficacy of the extract of Commiphora molmol, against Enterococcus faecalis and Fusobacterium nucleatum, with sodium hypochlorite (NaOCl).T he dehydrated oleo-gum resin of Commiphora molmol was extracted by using 70% ethanol and was suspended in 99.8% dimethyl (...) ) results showed that 0.03mg/μL myrrh extract and 2.5% sodium hypochlorite significantly reduced bacterial growth at both 30 and 60 minutes of different treatments of root canals, compared to DMSO group (negative control) and the antibiotic group (positive group).Myrrh extract was proven to have considerable antibacterial activity against both F. nucleatum and E. faecalis.

2019 Evidence-based Complementary and Alternative Medicine (eCAM)

1912. Studies on Antibacterial Activity and Diversity of Cultivable Actinobacteria Isolated from Mangrove Soil in Futian and Maoweihai of China. Full Text available with Trip Pro

Studies on Antibacterial Activity and Diversity of Cultivable Actinobacteria Isolated from Mangrove Soil in Futian and Maoweihai of China. Mangrove is a rich and underexploited ecosystem with great microbial diversity for discovery of novel and chemically diverse antimicrobial compounds. The goal of the study was to explore the pharmaceutical actinobacterial resources from mangrove soil and gain insight into the diversity and novelty of cultivable actinobacteria. Consequently, 10 mangrove soil (...) proportions. Notably, 11 strains showed relatively low 16S rRNA gene sequence similarities (< 98.65 %) with validly described species. Based on genotypic analyses and phenotypic characteristics, 115 out of the 539 actinobacterial strains were chosen as representative strains to test their antibacterial activities against "ESKAPE" bacteria by agar well diffusion method and antibacterial mechanism by the double fluorescent protein reporter system. Fifty-four strains in 23 genera, including 2 potential new

2019 Evidence-based Complementary and Alternative Medicine (eCAM)

1913. Young doctors' perspectives on antibiotic use and resistance: a multinational and inter-specialty cross-sectional European Society of Clinical Microbiology and Infectious Diseases (ESCMID) survey. Full Text available with Trip Pro

Young doctors' perspectives on antibiotic use and resistance: a multinational and inter-specialty cross-sectional European Society of Clinical Microbiology and Infectious Diseases (ESCMID) survey. Postgraduate training has the potential to shape the prescribing practices of young doctors.To investigate the practices, attitudes and beliefs on antibiotic use and resistance in young doctors of different specialties.We performed an international web-based exploratory survey. Principal component (...) analysis (PCA) and bivariate and multivariate [analysis of variance (ANOVA)] analyses were used to investigate differences between young doctors according to their country of specialization, specialty, year of training and gender.Of the 2366 participants from France, Greece, Italy, Portugal, Slovenia and Spain, 54.2% of young doctors prescribed antibiotics predominantly as instructed by a mentor. Associations between the variability of answers and the country of training were observed across most

2019 Journal of Antimicrobial Chemotherapy

1914. Short-course antibiotic treatment of bone and joint infections in children: a retrospective study at Montpellier University Hospital from 2009 to 2013. (Abstract)

% of the cases and the secondary surgical revision rate was 7%.The results of this study are comparable to those reported for evaluations of prolonged antibiotic therapy protocols, thus indicating that a common short-term antimicrobial therapy for the management of both osteomyelitis and septic arthritis (minimum of 15 days) is a viable option for treating AHBJI in children. Further prospective studies to confirm these findings are hence warranted.© The Author(s) 2019. Published by Oxford University Press (...) Short-course antibiotic treatment of bone and joint infections in children: a retrospective study at Montpellier University Hospital from 2009 to 2013. Acute haematogenous bone and joint infections (AHBJI) represent a diagnostic and therapeutic emergency in children, with significant potential sequelae in the case of delayed treatment. Although historically the recommendations for treatment have been based on surgery and prolonged antibiotic therapy, recent studies have demonstrated that short

2019 Journal of Antimicrobial Chemotherapy

1915. Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany. Full Text available with Trip Pro

Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany. The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS (...) QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline.Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n = 4310) were included in the study

2019 Journal of Antimicrobial Chemotherapy

1916. The effectiveness of repeating a social norm feedback intervention to high prescribers of antibiotics in general practice: a national regression discontinuity design. Full Text available with Trip Pro

The effectiveness of repeating a social norm feedback intervention to high prescribers of antibiotics in general practice: a national regression discontinuity design. Unnecessary antibiotic prescribing contributes to antimicrobial resistance. A randomized controlled trial in 2014-15 showed that a letter from England's Chief Medical Officer (CMO) to high-prescribing GPs, giving feedback about their prescribing relative to the norm, decreased antibiotic prescribing. The CMO sent further feedback (...) is robust to different specifications of the model.Social norm feedback from a high-profile messenger continues to be effective when repeated. It can substantially reduce antibiotic prescribing at low cost and on a national scale. Therefore, it is a worthwhile addition to antimicrobial stewardship programmes.© Crown copyright 2019.

2019 Journal of Antimicrobial Chemotherapy

1917. Celecoxib potentiates antibiotic uptake by altering membrane potential and permeability in Staphylococcus aureus. Full Text available with Trip Pro

Celecoxib potentiates antibiotic uptake by altering membrane potential and permeability in Staphylococcus aureus. We have shown previously that celecoxib enhances the antibacterial effect of antibiotics and has sensitized drug-resistant bacteria to antibiotics at low concentrations using in vitro and in vivo model systems and also using clinically isolated ESKAPE pathogens.To identify the mechanism of action of celecoxib in potentiating the effect of antibiotics on bacteria.Toxicogenomic (...) celecoxib and ampicillin, which might help in the entry of antibiotics.Although further studies are warranted, here we report that celecoxib alters membrane potential and permeability, specifically by affecting the Na+/K+ ion transporter, and thereby increases the uptake of ampicillin by S. aureus.© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

2019 Journal of Antimicrobial Chemotherapy

1918. Opportunities to reduce antibiotic prescribing for patients with COPD in primary care: a cohort study using electronic health records from the Clinical Practice Research Datalink (CPRD). Full Text available with Trip Pro

COPD. Antibiotic stewardship should focus on the dual goals of safely reducing the volume of prescribing in patients with mild to moderate COPD, and optimizing prescribing in patients with severe disease who are at significant risk of drug resistance.© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. (...) Opportunities to reduce antibiotic prescribing for patients with COPD in primary care: a cohort study using electronic health records from the Clinical Practice Research Datalink (CPRD). In primary care there is uncertainty about which patients with acute exacerbations of COPD (AECOPD) benefit from antibiotics.To identify which types of COPD patients get the most antibiotics in primary care to support targeted antibiotic stewardship.Observational study of COPD patients using a large English

2019 Journal of Antimicrobial Chemotherapy

1919. Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment. (Abstract)

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment. Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption.To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV (...) patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence.In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae

2019 Journal of Antimicrobial Chemotherapy

1920. Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: a propensity score-based analysis. (Abstract)

was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition.Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use (...) of these drugs appears to be an antibiotic stewardship opportunity.© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

2019 Journal of Antimicrobial Chemotherapy

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