scholarly journals 2208. Development and Evaluation of Predictive Models for Estimating Infection Susceptibility to Empiric Treatment Regimens Among Patients with Pneumonia in Intensive Care Units

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S753-S753
Author(s):  
Courtney M Dewart ◽  
Erinn Hade ◽  
Yuan Gao ◽  
Protiva Rahman ◽  
Mark Lustberg ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Predictive Models ◽  
Pathogenic Bacteria ◽  
Goodness Of Fit ◽  
Specific Treatment ◽  
Penalized Regression ◽  
Diagnostic Process ◽  
Antibiotic Prescribing ◽  
Treatment Regimens ◽  
Infection Susceptibility

Abstract Background Predictive models for empiric antibiotic prescribing often estimate the probability of infection with multidrug-resistant organisms. In this work, we developed models to predict coverage of specific treatment regimens to better target antibiotics to high- and low-risk patients. Methods We established a retrospective cohort of adults admitted to the ICU in a 1,300-bed teaching hospital from November 1, 2011 to June 30, 2016. We included patients with a diagnosis of pneumonia and positive respiratory culture collected during their ICU stay. We collected demographics, comorbidities, and medical history from the electronic health record. We evaluated three penalized regression methods for predicting infection susceptibility to 11 treatment regimens: least absolute selection and shrinkage operator (LASSO), minimax concave penalty (MCP), and smoothly clipped absolute deviation (SCAD). We developed models for susceptibility prediction at two stages of the diagnostic process: for all pathogenic bacteria and for infections with Gram-negative organisms only. We selected final models based on higher area under the receiver operating characteristic (AUROC), acceptable goodness of fit, lower variability of the AUROCs in the cross-validation run, and fewer predictors. Results Among 1,917 cases of pneumonia, 54 different pathogens were identified. The most frequently isolated organisms were: Pseudomonas aeruginosa (16.6%), methicillin-resistant Staphylococcus aureus (16.1%), and Staphylococcus aureus (13.5%). Frequently selected variables included age, Elixhauser score, tracheostomy status, recent antimicrobial use, and prior infection with a carbapenem-resistant organism. All final models used MCP or SCAD methods. Point estimates for the AUROCs in the training set ranged from 0.70 to 0.80, and estimates in the internal validation set ranged from 0.64 to 0.77. Conclusion MCP and SCAD outperformed LASSO. For some regimens, models predicted infection susceptibility with fair accuracy. These models have potential to help antibiotic stewardship efforts to better target appropriate antibiotic use. Disclosures All authors: No reported disclosures.

scholarly journals Structural basis of inhibition of a transporter from Staphylococcus aureus, NorC, through a single-domain camelid antibody

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sushant Kumar ◽  
Arunabh Athreya ◽  
Ashutosh Gulati ◽  
Rahul Mony Nair ◽  
Ithayaraja Mahendran ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Major Facilitator Superfamily ◽  
Single Domain ◽  
Fluoroquinolone Resistance ◽  
Structural Basis ◽  
Antibody Complex ◽  
Complementarity Determining Regions ◽  
Major Facilitator ◽  
Alternating Access

AbstractTransporters play vital roles in acquiring antimicrobial resistance among pathogenic bacteria. In this study, we report the X-ray structure of NorC, a 14-transmembrane major facilitator superfamily member that is implicated in fluoroquinolone resistance in drug-resistant Staphylococcus aureus strains, at a resolution of 3.6 Å. The NorC structure was determined in complex with a single-domain camelid antibody that interacts at the extracellular face of the transporter and stabilizes it in an outward-open conformation. The complementarity determining regions of the antibody enter and block solvent access to the interior of the vestibule, thereby inhibiting alternating-access. NorC specifically interacts with an organic cation, tetraphenylphosphonium, although it does not demonstrate an ability to transport it. The interaction is compromised in the presence of NorC-antibody complex, consequently establishing a strategy to detect and block NorC and related transporters through the use of single-domain camelid antibodies.

scholarly journals Antimicrobial Efficacy and Spectrum of Phosphorous-Fluorine Co-Doped TiO2 Nanoparticles on the Foodborne Pathogenic Bacteria Campylobacter jejuni, Salmonella Typhimurium, Enterohaemorrhagic E. coli, Yersinia enterocolitica, Shewanella putrefaciens, Listeria monocytogenes and Staphylococcus aureus

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1786
Author(s):  
György Schneider ◽  
Bettina Schweitzer ◽  
Anita Steinbach ◽  
Botond Zsombor Pertics ◽  
Alysia Cox ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Campylobacter Jejuni ◽  
Food Industry ◽  
Pathogenic Bacteria ◽  
Antibacterial Activities ◽  
Tio2 Nps ◽  
E Coli ◽  
Foodborne Pathogenic Bacteria ◽  
And Staphylococcus Aureus ◽  
Co Doped

Contamination of meats and meat products with foodborne pathogenic bacteria raises serious safety issues in the food industry. The antibacterial activities of phosphorous-fluorine co-doped TiO2 nanoparticles (PF-TiO2) were investigated against seven foodborne pathogenic bacteria: Campylobacter jejuni, Salmonella Typhimurium, Enterohaemorrhagic E. coli, Yersinia enterocolitica, Shewanella putrefaciens, Listeria monocytogenes and Staphylococcus aureus. PF-TiO2 NPs were synthesized hydrothermally at 250 °C for 1, 3, 6 or 12 h, and then tested at three different concentrations (500 μg/mL, 100 μg/mL, 20 μg/mL) for the inactivation of foodborne bacteria under UVA irradiation, daylight exposure or dark conditions. The antibacterial efficacies were compared after 30 min of exposure to light. Distinct differences in the antibacterial activities of the PF-TiO2 NPs, and the susceptibilities of tested foodborne pathogenic bacterium species were found. PF-TiO2/3 h and PF-TiO2/6 h showed the highest antibacterial activity by decreasing the living bacterial cell number from ~106 by ~5 log (L. monocytogenes), ~4 log (EHEC), ~3 log (Y. enterolcolitca, S. putrefaciens) and ~2.5 log (S. aureus), along with complete eradication of C. jejuni and S. Typhimurium. Efficacy of PF-TiO2/1 h and PF-TiO2/12 h NPs was lower, typically causing a ~2–4 log decrease in colony forming units depending on the tested bacterium while the effect of PF-TiO2/0 h was comparable to P25 TiO2, a commercial TiO2 with high photocatalytic activity. Our results show that PF-co-doping of TiO2 NPs enhanced the antibacterial action against foodborne pathogenic bacteria and are potential candidates for use in the food industry as active surface components, potentially contributing to the production of meats that are safe for consumption.

scholarly journals Bodipy-Loaded Micelles Based on Polylactide as Surface Coating for Photodynamic Control of Staphylococcus aureus

Coatings ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 223
Author(s):  
Enrico Caruso ◽  
Viviana Teresa Orlandi ◽  
Miryam Chiara Malacarne ◽  
Eleonora Martegani ◽  
Chiara Scanferla ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Surface Coatings ◽  
Supramolecular System ◽  
Amphiphilic Copolymers ◽  
Oxygen Penetration ◽  
Short Period ◽  
Excellent Activity ◽  
Coating Matrix ◽  
Photodynamic Control

Decontaminating coating systems (DCSs) represent a challenge against pathogenic bacteria that may colonize hospital surfaces, causing several important infections. In this respect, surface coatings comprising photosensitizers (PSs) are promising but still controversial for several limitations. PSs act through a mechanism of antimicrobial photodynamic inactivation (aPDI) due to formation of reactive oxygen species (ROS) after light irradiation. However, ROS are partially deactivated during their diffusion through a coating matrix; moreover, coatings should allow oxygen penetration that in contact with the activated PS would generate 1O2, an active specie against bacteria. In the attempt to circumvent such constraints, we report a spray DCS made of micelles loaded with a PS belonging to the BODIPY family (2,6-diiodo-1,3,5,7-tetramethyl-8-(2,6-dichlorophenyl)-4,4′-difluoroboradiazaindacene) that is released in a controlled manner and then activated outside the coating. For this aim, we synthesized several amphiphilic copolymers (mPEG–(PLA)n), which form micelles, and established the most stable supramolecular system in terms of critical micelle concentration (CMC) and ∆Gf values. We found that micelles obtained from mPEG–(PLLA)2 were the most thermodynamically stable and able to release BODIPY in a relatively short period of time (about 80% in 6 h). Interestingly, the BODIPY released showed excellent activity against Staphylococcus aureus even at micromolar concentrations.

scholarly journals Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture

2005 ◽  
Vol 187 (2) ◽  
pp. 554-566 ◽  
Author(s):  
Lauren M. Mashburn ◽  
Amy M. Jett ◽  
Darrin R. Akins ◽  
Marvin Whiteley
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Iron Acquisition ◽  
Low Oxygen ◽  
Dialysis Membrane ◽  
Opportunistic Human Pathogen ◽  
The Impact

ABSTRACT Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen often infecting the lungs of individuals with the heritable disease cystic fibrosis and the peritoneum of individuals undergoing continuous ambulatory peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this study, a rat dialysis membrane peritoneal model was used to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo compared to in vitro controls. Included in this analysis are genes important for iron acquisition and growth in low-oxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa iron-regulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in this environment. We propose a model where P. aeruginosa lyses S. aureus and uses released iron for growth in low-iron environments.

scholarly journals Measurement of Effects of Antibiotics in Bioluminescent Staphylococcus aureus RN4220

2001 ◽  
Vol 45 (12) ◽  
pp. 3456-3461 ◽  
Author(s):  
Mervi Tenhami ◽  
Kaisa Hakkila ◽  
Matti Karp
Keyword(s):  
Staphylococcus Aureus ◽  
High Throughput Screening ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Light Emission ◽  
Detection System ◽  
Firefly Luciferase ◽  
Luciferase Reporter ◽  
Luciferase Expression ◽  
Luciferase Reporter Gene

ABSTRACT The spread of antibiotic resistance among pathogenic bacteria is a serious threat to humans and animals. Therefore, unnecessary use should be minimized, and new antimicrobial agents with novel mechanisms of action are needed. We have developed an efficient method for measuring the action of antibiotics which is applied to a gram-positive strain,Staphylococcus aureus RN4220. The method utilizes the firefly luciferase reporter gene coupled to the metal-induciblecadA promoter in a plasmid, pTOO24. Correctly timed induction by micromolar concentrations of antimonite rapidly triggers the luciferase gene transcription and translation. This sensitizes the detection system to the action of antibiotics, and especially for transcriptional and translational inhibitors. We show the results for 11 model antibiotics with the present approach and compare them to an analytical setup with a strain where luciferase expression is under the regulation of a constitutive promoter giving only a report of metabolic inhibition. The measurement of light emission from intact living cells is shown to correlate extremely well (r = 0.99) with the conventional overnight growth inhibition measurement. Four of the antibiotics were within a 20% concentration range and four were within a 60% concentration range of the drugs tested. This approach shortens the assay time needed, and it can be performed in 1 to 4 h, depending on the sensitivity needed. Furthermore, the assay can be automatized for high-throughput screening by the pharmaceutical industry.

scholarly journals Activity of Gatifloxacin in an In Vitro Pharmacokinetic-Pharmacodynamic Model against Staphylococcus aureus Strains either Susceptible to Ciprofloxacin or Exhibiting Various Levels and Mechanisms of Ciprofloxacin Resistance

2006 ◽  
Vol 50 (6) ◽  
pp. 1931-1936 ◽  
Author(s):  
Boubakar B. Ba ◽  
Corinne Arpin ◽  
Céline Vidaillac ◽  
Arnaud Chausse ◽  
Marie-Claude Saux ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Goodness Of Fit ◽  
Reference Strain ◽  
Pharmacodynamic Model ◽  
Bacterial Killing ◽  
Β Phase ◽  
Ciprofloxacin Resistance ◽  
Total Elimination ◽  
Gram Positive Cocci

ABSTRACT Gatifloxacin (GAT) is a new 8-methoxy fluoroquinolone with enhanced activity against gram-positive cocci. Its activity was studied in an in vitro pharmacokinetic-pharmacodynamic model against five Staphylococcus aureus strains, either susceptible to ciprofloxacin or exhibiting various levels and mechanisms of ciprofloxacin (CIP) resistance: the ATCC 25923 reference strain (MICs of CIP and GAT: 0.5 and 0.1 μg/ml, respectively), its efflux mutant SA-1 (16 and 0.5 μg/ml; mutation in the norA promoter region), and three clinical strains, Sa2102 (2 and 0.2 μg/ml), Sa2667 (4 and 0.5 μg/ml), and Sa2669 (16 and 1 μg/ml), carrying mutations in the grlA (Ser80Tyr or Phe) and gyrA (Ser84Ala) quinolone resistance-determining regions (QRDRs) for Sa2669. Plasmatic pharmacokinetic profiles after daily 1-h perfusion of 400 mg for 48 h were accurately simulated. Thus, mean maximum concentration of drug in serum values for the two administration intervals were 5.36 and 5.80 μg/ml, respectively, and the corresponding half-life at β-phase values were 8.68 and 7.80 h (goodness of fit coefficient, >0.98). Therapeutic concentrations of GAT allowed the complete eradication of the susceptible strain within 12 h (difference between the bacterial counts at the beginning of the treatment and at a defined time: −2.18 at the 1-h time point [t 1] and −6.80 at t 24 and t 48; the bacterial killing and regrowth curve from 0 to 48 h was 30.2 h × log CFU/milliliter). However, mutants (M) with GAT MICs increased by 4- to 40-fold were selected from the other strains. They acquired mutations either supplementary (MSa2102 and MSa2667) or different (Ala84Val for MSa2669) in gyrA or in both gyrA and grlA QRDRs (MSA-1). MSa2667 additionally overproduced efflux system(s) without norA promoter modification. Thus, GAT properties should allow the total elimination of ciprofloxacin-susceptible S. aureus, but resistant mutants might emerge from strains showing reduced susceptibility to older fluoroquinolones independently of the first-step mutation(s).

Epigenetics In Autoimmune Disease

2018 ◽  
Author(s):  
Matlock A Jeffries
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Autoimmune Disease ◽  
Noncoding Rna ◽  
Specific Treatment ◽  
Cell Types ◽  
Response To Therapy ◽  
Human Immune System ◽  
Treatment Regimens ◽  
New Research

Autoimmunity refers to a pathologic state of immunologic dysregulation in which the human immune system turns inward, attacking healthy tissues. The key step in this process is a break of self-immune tolerance. Recent studies have implicated dysregulation of gene expression via altered epigenetic control as a key mechanism in the development and promotion of autoimmunity. Epigenetics is defined as heritable changes in gene expression as a result of modification of DNA methylation, histone side chains, and noncoding RNA. Studies examining identical twins discordant for lupus, for example, were among the first to identify alterations in DNA methylation leading to lupus. Histone side-chain changes have been studied extensively in rheumatoid arthritis (RA), and many pathogenic cell types in RA exhibit a hyperacetylation phenotype. Finally, new research in the noncoding RNA field has not only uncovered potentially targetable pathways (e.g., miR-155) but may lead to the development of new diagnostic and prognostic biomarkers, helping physicians better tailor specific treatment regimens to improve response to therapy in autoimmune disease.   This review contains 4 figures, 1 table and 47 references Key Words: autoimmunity, big data, biomarkers, computational biology, DNA methylation, epigenetics, histone acetylation, histone methylation, microRNA, noncoding RNA

scholarly journals Identification and antibiogram study of bacterial species isolated from milk samples of different locations in Bangladesh

2016 ◽  
Vol 1 (3) ◽  
pp. 457-462 ◽  
Author(s):  
Md Nuruzzaman Munsi ◽  
Nathu Ram Sarker ◽  
Razia Khatun ◽  
Mohammed Khorshed Alam
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Salmonella Typhi ◽  
Diffusion Method ◽  
Biochemical Tests ◽  
Public Health Importance ◽  
Milk Samples ◽  
First Choice

Cow’s milk containing pathogenic bacteria is an important threat to the consumers. The objectives of the present study were to identify the bacterial agents of public health importance in milk samples (n=35) of different locations and to determine their sensitivity to different antibiotics. The milk samples were collected and transported aseptically and subsequently allowed for culture in bacteriological media, Gram’s staining and biochemical tests for the identification of bacterial species. The bacteria identified were Staphylococcus aureus, Escherichia coli and Salmonella typhi, and their prevalence, in case of vendor milk specimens (n=28), were 96.43%, 53.57% and 35.71% respectively, and of brand milk specimens (n=7), were 42.86 %, 28.57% and 0%, respectively. This suggests that cautionary measures should be taken for quality milk production and consumption. The antibiotic sensitivity test was done by disc diffusion method and the average inhibition zones, in case of Staphylococcus aureus, were 32 mm for oxytetracycline, 26 mm for amoxicillin, 35 mm for ciprofloxacin, 27 mm for cefotaxime, 30 mm for ceftriaxone, 30 mm for azithromycin, and 26 mm for erythromycin; in case of Escherichia coli, were 5 mm for oxytetracycline, 9 mm for amoxicillin, 22 mm for ciprofloxacin, 30 mm for cefotaxime, 31 mm for ceftriaxone, 15 mm for azithromycin, and 0 mm for erythromycin; in case of Salmonella typhi., were 25 mm for oxytetracycline, 24 mm for amoxicillin, 38 mm for ciprofloxacin, 31 mm for cefotaxime, 34 mm for ceftriaxone, 24 mm for azithromycin, and 0 mm for erythromycin. Therefore, ciprofloxacin and ceftriaxone may be the antibiotics of first choice, and cefotaxime and azithromycin may be the second choice among the test antibiotics for the treatment of illness caused by these bacteria.Asian J. Med. Biol. Res. December 2015, 1(3): 457-462

scholarly journals The Relationship between Colonization by Moraxella catarrhalis and Tonsillar Hypertrophy

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Mirela C. M. Prates ◽  
Edwin Tamashiro ◽  
José L. Proenca-Modena ◽  
Miriã F. Criado ◽  
Tamara H. Saturno ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Pathogenic Bacteria ◽  
Simultaneous Detection ◽  
Tonsillar Hypertrophy ◽  
Palatine Tonsils ◽  
Adenotonsillar Hypertrophy

We sought to investigate the prevalence of potentially pathogenic bacteria in secretions and tonsillar tissues of children with chronic adenotonsillitis hypertrophy compared to controls. Prospective case-control study comparing patients between 2 and 12 years old who underwent adenotonsillectomy due to chronic adenotonsillar hypertrophy to children without disease. We compared detection of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis by real-time PCR in palatine tonsils, adenoids, and nasopharyngeal washes obtained from 37 children with and 14 without adenotonsillar hypertrophy. We found high frequency (>50%) of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa in both groups of patients. Although different sampling sites can be infected with more than one bacterium and some bacteria can be detected in different tissues in the same patient, adenoids, palatine tonsils, and nasopharyngeal washes were not uniformly infected by the same bacteria. Adenoids and palatine tonsils of patients with severe adenotonsillar hypertrophy had higher rates of bacterial coinfection. There was good correlation of detection of Moraxella catarrhalis in different sampling sites in patients with more severe tonsillar hypertrophy, suggesting that Moraxella catarrhalis may be associated with the development of more severe hypertrophy, that inflammatory conditions favor colonization by this agent. Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis are frequently detected in palatine tonsils, adenoids, and nasopharyngeal washes in children. Simultaneous detection of Moraxella catarrhalis in adenoids, palatine tonsils, and nasopharyngeal washes was correlated with more severe tonsillar hypertrophy.

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