scholarly journals Concise synthesis of spergualin-inspired molecules with broad-spectrum antibiotic activity

MedChemComm ◽  
2015 ◽  
Vol 6 (5) ◽  
pp. 912-918 ◽  
Author(s):  
Victoria A. Assimon ◽  
Hao Shao ◽  
Sylvie Garneau-Tsodikova ◽  
Jason E. Gestwicki
Keyword(s):  
Natural Product ◽  
Broad Spectrum ◽  
Antibiotic Activity ◽  
Broad Spectrum Antibiotic ◽  
Broad Spectrum Antibiotics ◽  
Privileged Structure

There is a growing need to identify new, broad-spectrum antibiotics. Here, we report a concise route to an antibiotic based on the privileged structure of the natural product spergualin.

scholarly journals Trends in Antibiotic Prescribing in Out-of-Hours Primary Care in England from January 2016 to June 2020 to Understand Behaviours during the First Wave of COVID-19

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 32
Author(s):  
Nina J. Zhu ◽  
Monsey McLeod ◽  
Cliodna A. M. McNulty ◽  
Donna M. Lecky ◽  
Alison H. Holmes ◽  
...  
Keyword(s):  
Primary Care ◽  
Time Series ◽  
Patient Outcomes ◽  
Broad Spectrum ◽  
Antibiotic Prescribing ◽  
Broad Spectrum Antibiotic ◽  
Out Of Hours ◽  
Broad Spectrum Antibiotics ◽  
National Quality ◽  
General Practices

We describe the trend of antibiotic prescribing in out-of-hours (OOH) general practices (GP) before and during England’s first wave of the COVID-19 pandemic. We analysed practice-level prescribing records between January 2016 to June 2020 to report the trends for the total prescribing volume, prescribing of broad-spectrum antibiotics and key agents included in the national Quality Premium. We performed a time-series analysis to detect measurable changes in the prescribing volume associated with COVID-19. Before COVID-19, the total prescribing volume and the percentage of broad-spectrum antibiotics continued to decrease in-hours (IH). The prescribing of broad-spectrum antibiotics was higher in OOH (OOH: 10.1%, IH: 8.7%), but a consistent decrease in the trimethoprim-to-nitrofurantoin ratio was observed OOH. The OOH antibiotic prescribing volume diverged from the historical trend in March 2020 and started to decrease by 5088 items per month. Broad-spectrum antibiotic prescribing started to increase in OOH and IH. In OOH, co-amoxiclav and doxycycline peaked in March to May in 2020, which was out of sync with seasonality peaks (Winter) in previous years. While this increase might be explained by the implementation of the national guideline to use co-amoxiclav and doxycycline to manage pneumonia in the community during COVID-19, further investigation is required to see whether the observed reduction in OOH antibiotic prescribing persists and how this reduction might influence antimicrobial resistance and patient outcomes.

Quantifying Empiric Antibiotic Use in US Children’s Hospitals

2021 ◽  
Author(s):  
Kathleen Chiotos ◽  
Lauren D’Arinzo ◽  
Eimear Kitt ◽  
Rachael Ross ◽  
Jeffrey S. Gerber
Keyword(s):  
Broad Spectrum ◽  
Antibiotic Use ◽  
Level Variation ◽  
Hospital Level ◽  
Broad Spectrum Antibiotic ◽  
Children's Hospitals ◽  
Broad Spectrum Antibiotics ◽  
Children’S Hospitals ◽  
Days Of Therapy ◽  
Rule Out

OBJECTIVES Empirical broad-spectrum antibiotics are routinely administered for short durations to children with suspected bacteremia while awaiting blood culture results. Our aim for this study was to estimate the proportion of broad-spectrum antibiotic use accounted for by these “rule-outs.” METHODS The Pediatric Health Information System was used to identify children aged 3 months to 20 years hospitalized between July 2016 and June 2017 who received broad-spectrum antibiotics for suspected bacteremia. Using an electronic definition for a rule-out, we estimated the proportion of all broad-spectrum antibiotic days of therapy accounted for by this indication. Clinical and demographic characteristics, as well as antibiotic choice, are reported descriptively. RESULTS A total of 67 032 episodes of suspected bacteremia across 42 hospitals were identified. From these, 34 909 (52%) patients were classified as having received an antibiotic treatment course, and 32 123 patients (48%) underwent an antibiotic rule-out without a subsequent treatment course. Antibiotics prescribed for rule-outs accounted for 12% of all broad-spectrum antibiotic days of therapy. Third-generation cephalosporins and vancomycin were the most commonly prescribed antibiotics, and substantial hospital-level variation in vancomycin use was identified (range: 16%–58% of suspected bacteremia episodes). CONCLUSIONS Broad-spectrum intravenous antibiotic use for rule-out infections appears common across children’s hospitals, with substantial hospital-level variation in the use of vancomycin in particular. Antibiotic stewardship programs focused on intervening on antibiotics prescribed for longer durations may consider this novel opportunity to further standardize antibiotic regimens and reduce antibiotic exposure.

scholarly journals 2422. Effectiveness of a Probiotic for Primary Prevention of Clostridium difficile Infection and Antibiotic-Associated Diarrhea among Hospitalized Patients Receiving Broad-Spectrum Antibiotics

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S836-S837
Author(s):  
Khanh-Linh Le ◽  
Heather Young ◽  
Timothy C Jenkins ◽  
Robert Tapia ◽  
Katherine C Shihadeh
Keyword(s):  
Primary Prevention ◽  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Broad Spectrum ◽  
Hospitalized Patients ◽  
Broad Spectrum Antibiotic ◽  
Probiotic Group ◽  
Broad Spectrum Antibiotics ◽  
Days Of Therapy ◽  
Antibiotic Associated Diarrhea

Abstract Background Prior to 2016, Denver Health Medical Center had a higher-than-expected rate of hospital onset Clostridium difficile infection (HO-CDI). A multifaceted CDI prevention plan was implemented, including the use of a probiotic as primary prevention for HO-CDI and antibiotic-associated diarrhea (AAD) in inpatients receiving broad-spectrum antibiotics. We aimed to study the effectiveness of probiotic use in this clinical context. Methods During the intervention, inpatient orders for a broad-spectrum antibiotic triggered a best practice advisory recommending once daily co-administration of 100 billion units of a probiotic containing Lactobacillus casei, L. rhamnosus, and L. acidophilus (BioK+ ®). To evaluate effectiveness and safety of this intervention, we performed a retrospective cohort study including adult inpatients who received > 24 hours of a broad-spectrum antibiotic between April 2016 and March 2018. The primary endpoint was the incidence of HO-CDI (> 3 days after admission) compared between patients who received antibiotics alone vs. antibiotics plus the probiotic. Secondary endpoints were the incidence of AAD, defined as a negative CDI test after antibiotic initiation, and the incidence of Lactobacillus species identified in clinical cultures. Results 3,291 patients were included; 1,835 received antibiotics alone and 1,456 received antibiotics plus the probiotic. Baseline characteristics between groups were similar, except patients in the antibiotic alone group had a greater incidence of cirrhosis and proton-pump inhibitor use (16.1% vs 10.1%, P < 0.001; 39.1% vs 31.5%, P < 0.001). Length of stay and antibiotic days of therapy were longer in the antibiotic plus probiotic group [6 days (IQR, 3–11) vs 6 days (IQR, 4–12), P = 0.014; 4 days (IQR, 3–7) vs 5 days (IQR, 3–7), P < 0.001]. The incidence of HO-CDI (37, 2% vs 35, 2.4%; P = 0.450) and AAD (231, 12.6% vs 199, 13.7%; P = 0.362) were similar between groups. Lactobacillus was identified in at least one clinical culture from 0.2% (3/1835) and 0.3% (4/1456) of patients in the antibiotic alone group and antibiotic plus probiotic group, respectively (P = 0.497). Conclusion In hospitalized patients receiving broad-spectrum antibiotics, co-administration of a probiotic did not appear to reduce the incidence of HO-CDI or AAD. Disclosures All authors: No reported disclosures.

scholarly journals Small molecule inhibitors of trans-translation have broad-spectrum antibiotic activity

2013 ◽  
Vol 110 (25) ◽  
pp. 10282-10287 ◽  
Author(s):  
N. S. Ramadoss ◽  
J. N. Alumasa ◽  
L. Cheng ◽  
Y. Wang ◽  
S. Li ◽  
...  
Keyword(s):  
Small Molecule ◽  
Broad Spectrum ◽  
Small Molecule Inhibitors ◽  
Antibiotic Activity ◽  
Broad Spectrum Antibiotic

scholarly journals Biosynthesis of fosfomycin in pseudomonads reveals an unexpected enzymatic activity in the metallohydrolase superfamily

2021 ◽  
Vol 118 (23) ◽  
pp. e2019863118
Author(s):  
Max A. Simon ◽  
Chayanid Ongpipattanakul ◽  
Satish K. Nair ◽  
Wilfred A. van der Donk
Keyword(s):  
Enzymatic Activity ◽  
Natural Product ◽  
Pseudomonas Syringae ◽  
Broad Spectrum ◽  
Plant Pathogen ◽  
Biosynthetic Pathway ◽  
Systematic Evaluation ◽  
Oxidative Decarboxylation ◽  
Broad Spectrum Antibiotic ◽  
New Class

The epoxide-containing phosphonate natural product fosfomycin is a broad-spectrum antibiotic used in the treatment of cystitis. Fosfomycin is produced by both the plant pathogen Pseudomonas syringae and soil-dwelling streptomycetes. While the streptomycete pathway has recently been fully elucidated, the pseudomonad pathway is still mostly elusive. Through a systematic evaluation of heterologous expression of putative biosynthetic enzymes, we identified the central enzyme responsible for completing the biosynthetic pathway in pseudomonads. The missing transformation involves the oxidative decarboxylation of the intermediate 2-phosphonomethylmalate to a new intermediate, 3-oxo-4-phosphonobutanoate, by PsfC. Crystallographic studies reveal that PsfC unexpectedly belongs to a new class of diiron metalloenzymes that are part of the polymerase and histidinol phosphatase superfamily.

scholarly journals 226. Evaluating the Unnecessary Use of Intravenous Broad-Spectrum Antibiotics in Patients Based on Systemic Inflammatory Response Syndrome Criteria in the Emergency Department (ED)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S114-S114
Author(s):  
Esther Y Bae ◽  
Marguerite Monogue ◽  
Tiffeny T Smith
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Bacterial Infection ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Antibiotic Use ◽  
Systemic Inflammatory Response ◽  
Broad Spectrum Antibiotic ◽  
Suspected Sepsis ◽  
Broad Spectrum Antibiotics

Abstract Background Recognition of sepsis frequently occurs in the ED. To demonstrate the need to optimize antibiotic use for suspected sepsis and evaluate the reliability of systemic inflammatory response syndrome (SIRS) criteria in predicting bacterial infection, we quantified the rate of unnecessary intravenous (IV) broad-spectrum antibiotic use for suspected sepsis in the ED at an academic medical center. Methods Adult patients who were admitted to the ED between January 2018 and June 2018 with suspected sepsis (≥ 2 SIRS) and received ≥ 1 dose of IV broad-spectrum antibiotic were included in this retrospective study. The presence of bacterial infection was determined using Centers for Disease Control and Prevention (CDC)/National Healthcare Safety Network (NHSN) definitions, microbiologic, radiographic, and laboratory findings. Suspected infections lacked microbiologic data. The primary outcome was the percentage of confirmed and suspected infections. Secondary outcomes included 90-day Clostridioides difficile infection (CDI) and 90-day drug-resistant organism (DRO) infections. Results A total of 218 patients were included. The percentages of confirmed/suspected and absence of bacterial infections were 63.8% and 36.2%, respectively. Elevated SIRS (≥ 2) and Quick Sequential Organ Failure Assessment (qSOFA; ≥ 2) scores were not associated with the presence of bacterial infections. 82% of patients were discharged from the ED. Antibiotic exposure in days of therapy in the ED and/or hospital admission did not significantly vary between patients with confirmed/suspected bacterial infection and those with absence of bacterial infections. Among patients who lacked evidence of bacterial infections, 44% were prescribed outpatient antibiotics after being discharged from the ED. 90-day CDI and DRO infections were identified in 7 and 6 patients, respectively, regardless of the presence of bacterial infections. Table 1. Baseline demographics of patients admitted to the ED with suspected sepsis Conclusion A third of the patients with suspected sepsis received IV broad-spectrum antibiotics in the ED but ultimately lacked bacterial infection. Our findings suggest that identification of bacterial infection and patients with sepsis using SIRS or qSOFA lack specificity and can lead to the overuse of unnecessary antibiotics in the ED. Disclosures All Authors: No reported disclosures

scholarly journals Relevant Features of Polypharmacologic Human-Target Antimicrobials Discovered by Machine-Learning Techniques

2020 ◽  
Vol 13 (9) ◽  
pp. 204
Author(s):  
Rodrigo A. Nava Lara ◽  
Jesús A. Beltrán ◽  
Carlos A. Brizuela ◽  
Gabriel Del Rio
Keyword(s):  
Machine Learning ◽  
Broad Spectrum ◽  
Human Microbiome ◽  
Antibiotic Activity ◽  
Machine Learning Techniques ◽  
Learning Approach ◽  
Broad Spectrum Antibiotic ◽  
Approach Training ◽  
Learning Techniques ◽  
Machine Learning Approach

Polypharmacologic human-targeted antimicrobials (polyHAM) are potentially useful in the treatment of complex human diseases where the microbiome is important (e.g., diabetes, hypertension). We previously reported a machine-learning approach to identify polyHAM from FDA-approved human targeted drugs using a heterologous approach (training with peptides and non-peptide compounds). Here we discover that polyHAM are more likely to be found among antimicrobials displaying a broad-spectrum antibiotic activity and that topological, but not chemical features, are most informative to classify this activity. A heterologous machine-learning approach was trained with broad-spectrum antimicrobials and tested with human metabolites; these metabolites were labeled as antimicrobials or non-antimicrobials based on a naïve text-mining approach. Human metabolites are not commonly recognized as antimicrobials yet circulate in the human body where microbes are found and our heterologous model was able to classify those with antimicrobial activity. These results provide the basis to develop applications aimed to design human diets that purposely alter metabolic compounds proportions as a way to control human microbiome.

EFFECTS OF PENICILLIN AND BROAD-SPECTRUM ANTIBIOTICS ON THE EMERGENCE OF A GRAM-NEGATIVE BACILLARY FLORA IN THE UPPER RESPIRATORY TRACT OF INFANTS

PEDIATRICS ◽  
1952 ◽  
Vol 9 (5) ◽  
pp. 572-576
Author(s):  
ROBERT S. MCCURDY ◽  
ERWIN NETER
Keyword(s):  
Respiratory Tract ◽  
Broad Spectrum ◽  
Clinical Manifestations ◽  
Upper Respiratory Tract ◽  
Broad Spectrum Antibiotic ◽  
Gram Negative ◽  
E Coli ◽  
Broad Spectrum Antibiotics ◽  
Upper Respiratory ◽  
Aerobic Flora

A study was undertaken on 107 infants to determine the effect of penicillin and broad-spectrum antibiotics (aureomycin, chloromycetin and terramycin), alone and in combination, on the emergence of a predominant gram-negative, bacillary flora of the upper respiratory tract. The following data were obtained: 1. Such a change of the flora took place in 4 out of 12 patients treated with penicillin, 15 out of 22 treated with penicillin and a broad-spectrum antibiotic, and in only 4 out of 21 infants who received a broad-spectrum antibiotic exclusively. 2. Of the 32 cases whose flora had thus changed, members of the E. coli-A. aerogenes group were found in 30 instances, members of the genus Proteus in 3; Ps. aeruginosa in 2; Paracolobactrum in 1; and combinations thereof in four cases. 3. This change of the flora took place in 18 out of 71 infants suffering from respiratory infection and in 14 out of 36 children suffering from other diseases. 4. Reappearance of clinical manifestations was observed in 6 out of 19 patients whose respiratory tract flora changed following the use of penicillin and in none of the four individuals who were treated with a broad-spectrum antibiotic alone. In view of the small number of cases this observation requires confirmation. 5. It is concluded that in infants the use of penicillin used in conjunction with a broad-spectrum antibiotic is followed rather frequently by the emergence in the upper respiratory tract of a predominant gram-negative, bacillary, aerobic flora; such a change occurs less frequently after the use of a broad-spectrum antibiotic alone. The clinical significance of these data is discussed.

scholarly journals Broad spectrum antibiotic activity of skin-PYY

FEBS Letters ◽  
1996 ◽  
Vol 380 (3) ◽  
pp. 237-240 ◽  
Author(s):  
Ionnis Vouldoukis ◽  
Yechiel Shai ◽  
Pierre Nicolas ◽  
Amram Mor
Keyword(s):  
Broad Spectrum ◽  
Antibiotic Activity ◽  
Broad Spectrum Antibiotic
Sign in / Sign up

Export Citation Format

Share Document