Thioamide Derivative of the Potent Antitubercular 2-(Decylsulfonyl)acetamide is Less Active Against Mycobacterium tuberculosis, but a More Potent Antistaphylococcal Agent

2018 ◽  
Vol 71 (9) ◽  
pp. 716
Author(s):  
Hsien-Kuo Sun ◽  
Angel Pang ◽  
Dylan C. Farr ◽  
Tamim Mosaiab ◽  
Warwick J. Britton ◽  
...  

Due to the prevalence of thioamides in antibacterial compounds, we chose to convert the amide in the antitubercular compound 2-(decylsulfonyl)acetamide to a thioamide using Lawesson’s reagent to study its activity against a range of microorganisms. This derivative (8) had significantly diminished activity against tuberculosis but slightly better activity than the parent compound against the Gram positive species Staphylococcus aureus. This activity against a second major pathogen is remarkable considering the structural simplicity of these compounds.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S60-S60
Author(s):  
Noor F Zaidan ◽  
Rachel S Britt ◽  
David Reynoso ◽  
R Scott Ferren

Abstract Background Pharmacist-driven protocols for utilization of methicillin-resistant Staphylococcus aureus (MRSA) nares screenings have shown to decrease duration of empiric gram-positive therapy and rates of acute kidney injury (AKI) in patients with respiratory infections. This study evaluated the impact of a pharmacist-driven MRSA nares screening protocol on duration of vancomycin or linezolid therapy (DT) in respiratory infections. Methods Patients aged 18 years and older with a medication order of vancomycin or linezolid for respiratory indication(s) were included. The MRSA nares screening protocol went into effect in October 2019. The protocol allowed pharmacists to order an MRSA nares polymerase chain reaction (PCR) for included patients, while the Antimicrobial Stewardship Program (ASP) made therapeutic recommendations for de-escalation of empiric gram-positive coverage based on negative MRSA nares screenings, if clinically appropriate. Data for the pre-intervention group was collected retrospectively for the months of October 2018 to March 2019. The post-intervention group data was collected prospectively for the months of October 2019 to March 2020. Results Ninety-seven patients were evaluated within both the pre-intervention group (n = 50) and post-intervention group (n = 57). Outcomes for DT (38.2 hours vs. 30.9 hours, P = 0.601) and AKI (20% vs. 14%, P = 0.4105) were not different before and after protocol implementation. A subgroup analysis revealed a significant reduction in DT within the pre- and post-MRSA PCR groups (38.2 hours vs. 24.8 hours, P = 0.0065) when pharmacist recommendations for de-escalation were accepted. Conclusion A pharmacist-driven MRSA nares screening protocol did not affect the duration of gram-positive therapy for respiratory indications. However, there was a reduction in DT when pharmacist-driven recommendations were accepted. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 41 (S1) ◽  
pp. s40-s40
Author(s):  
Hsiu Wu ◽  
Tyler Kratzer ◽  
Liang Zhou ◽  
Minn Soe ◽  
Jonathan Edwards ◽  
...  

Background: To provide a standardized, risk-adjusted method for summarizing antimicrobial use (AU), the Centers for Disease Control and Prevention developed the standardized antimicrobial administration ratio, an observed-to-predicted use ratio in which predicted use is estimated from a statistical model accounting for patient locations and hospital characteristics. The infection burden, which could drive AU, was not available for assessment. To inform AU risk adjustment, we evaluated the relationship between the burden of drug-resistant gram-positive infections and the use of anti-MRSA agents. Methods: We analyzed data from acute-care hospitals that reported ≥10 months of hospital-wide AU and microbiologic data to the National Healthcare Safety Network (NHSN) from January 2018 through June 2019. Hospital infection burden was estimated using the prevalence of deduplicated positive cultures per 1,000 admissions. Eligible cultures included blood and lower respiratory specimens that yielded oxacillin/cefoxitin–resistant Staphylococcus aureus (SA) and ampicillin-nonsusceptible enterococci, and cerebrospinal fluid that yielded SA. The anti-MRSA use rate is the total antimicrobial days of ceftaroline, dalbavancin, daptomycin, linezolid, oritavancin, quinupristin/dalfopristin, tedizolid, telavancin, and intravenous vancomycin per 1,000 days patients were present. AU rates were modeled using negative binomial regression assessing its association with infection burden and hospital characteristics. Results: Among 182 hospitals, the median (interquartile range, IQR) of anti-MRSA use rate was 86.3 (59.9–105.0), and the median (IQR) prevalence of drug-resistant gram-positive infections was 3.4 (2.1–4.8). Higher prevalence of drug-resistant gram-positive infections was associated with higher use of anti-MRSA agents after adjusting for facility type and percentage of beds in intensive care units (Table 1). Number of hospital beds, average length of stay, and medical school affiliation were nonsignificant. Conclusions: Prevalence of drug-resistant gram-positive infections was independently associated with the use of anti-MRSA agents. Infection burden should be used for risk adjustment in predicting the use of anti-MRSA agents. To make this possible, we recommend that hospitals reporting to NHSN’s AU Option also report microbiologic culture results.Funding: NoneDisclosures: None


Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 110
Author(s):  
Anna K. Riebisch ◽  
Sabrina Mühlen ◽  
Yan Yan Beer ◽  
Ingo Schmitz

Autophagy is a highly conserved and fundamental cellular process to maintain cellular homeostasis through recycling of defective organelles or proteins. In a response to intracellular pathogens, autophagy further acts as an innate immune response mechanism to eliminate pathogens. This review will discuss recent findings on autophagy as a reaction to intracellular pathogens, such as Salmonella typhimurium, Listeria monocytogenes, Mycobacterium tuberculosis, Staphylococcus aureus, and pathogenic Escherichia coli. Interestingly, while some of these bacteria have developed methods to use autophagy for their own benefit within the cell, others have developed fascinating mechanisms to evade recognition, to subvert the autophagic pathway, or to escape from autophagy.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S777-S778
Author(s):  
Arsheena Yassin ◽  
Christine Stavropoulos ◽  
Krystina L Woods ◽  
Jiashan Xu ◽  
Justin Carale ◽  
...  

Abstract Background Hand infections represent a major source of morbidity, which can result in hand stiffness and amputation. Early appropriate empiric antibiotic regimen may reduce the associated morbidity, hence the importance to examine local epidemiology. The aim of this study was to define the current epidemiology of adult hand infections at two urban hospitals in New York City. Methods We performed a double center, retrospective study of adult patients hospitalized from March 2018 to May 2020. Patients with positive cultures associated with the hand infections were included. Retrospectively, 100 patients were reviewed. Data on baseline demographic, clinical, surgical, microbiology, and treatment parameters were collected. Results Of the 100 patients, 76% were male, with median age of 47.5 years (35, 58.25) and average C-reactive protein (CRP) of 50.66 mg/L (± 64.64) on admission (see Table 1). Previous hospitalization within 1 year (38%), previous surgical procedures (39%) and recent IV medication use (26%) were common. 130 bacterial isolates were identified (see Table 2). The most frequent organisms were Gram-positive, with Methicillin susceptible Staphylococcus aureus (MSSA, 25.38%), Streptococcus species (20.08%), and Methicillin resistant Staphylococcus aureus (MRSA, 15.38%) being the most common. Gram-negative organisms were infrequent, with Haemophilus parainfluenzae (3.85%), Enterobacter cloacae (3.85) and Pseudomonas aeruginosa (3.08%) being the most prevalent. Of the 100 patients, 27% had polymicrobial infections, associated with trauma (6%), illicit IV use (6%) and unknown (7%) etiologies. Table 1: Baseline demographics and co-morbid conditions Table 2: Types and numbers of organisms in relation to etiologies Conclusion Within our population, the most common organisms associated with hand infections were Gram-positive, with Staphylococcus aureus and Streptococcus species being the most prevalent. Gram-negative pathogens were infrequently isolated. The results within this study can provide guidance to clinicians on assessing the appropriate empiric antibiotic regimen in patients with hand infections, and can serve as a basis for further studies identifying risk factors associated with isolation of organisms associated with hand infections. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 12 (03) ◽  
pp. 230-232
Author(s):  
Dhruv Mamtora ◽  
Sanjith Saseedharan ◽  
Ritika Rampal ◽  
Prashant Joshi ◽  
Pallavi Bhalekar ◽  
...  

Abstract Background Blood stream infections (BSIs) due to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality ranging from 10 to 60%. The current anti-MRSA agents have limitations with regards to safety and tolerability profile which limits their prolonged usage. Levonadifloxacin and its oral prodrug alalevonadifloxacin, a novel benzoquinolizine antibiotic, have recently been approved for acute bacterial skin and skin structure infections including diabetic foot infections and concurrent bacteremia in India. Methods The present study assessed the potency of levonadifloxacin, a novel benzoquinolizine antibiotic, against Gram-positive blood stream clinical isolates (n = 31) collected from January to June 2019 at a tertiary care hospital in Mumbai, India. The susceptibility of isolates to antibacterial agents was defined following the Clinical and Laboratory Standard Institute interpretive criteria (M100 E29). Results High prevalence of MRSA (62.5%), quinolone-resistant Staphylococcus aureus (QRSA) (87.5%), and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (82.35%) were observed among bacteremic isolates. Levonadifloxacin demonstrated potent activity against MRSA, QRSA, and MR-CoNS strains with significantly lower minimum inhibitory concentration MIC50/90 values of 0.5/1 mg/L as compared with levofloxacin (8/32 mg/L) and moxifloxacin (2/8 mg/L). Conclusion Potent bactericidal activity coupled with low MICs support usage of levonadifloxacin for the management of BSIs caused by multidrug resistant Gram-positive bacteria.


2016 ◽  
Vol 29 (5) ◽  
pp. 319 ◽  
Author(s):  
Joaquim Soares do Brito ◽  
António Tirado ◽  
Pedro Fernandes

<p><strong>Introduction:</strong> The term spondylodiscitis aims to describe any spinal infection. Medical treatment is the gold standard; nevertheless, surgical treatment can be indicated. The aim of this work was to study the epidemiological profile in a group of patients with spondylodiscitis surgically treated in the same medical institution between 1997 and 2013. <br /><strong>Material and Methods:</strong> Eighty five patients with spondylodiscitis were surgically treated in this period. The authors analysed clinical data and image studies for each patient.<br /><strong>Results:</strong> We treated 51 male and 34 female patients with an average age of 48 years old (min: 6 - max: 80). The lumbar spine was more often affected and <em>Mycobacterium tuberculosis</em> the most frequent pathogen. The number of cases through the years has been grossly stable, with a slight increase of dyscitis due to <em>Staphylococcus aureus</em> and decrease of the dyscitis without pathogen identification. Paravertebral abscess was identified in 39 patients and 17 had also neurological impairment, mostly located in the thoracic spine and with tuberculous aetheology. Immunosuppression was documented in 10 patients. <br /><strong>Discussion:</strong> In this epidemiologic study we found a tuberculous infection, male gender and young age predominance. Despite a relative constant number of patients operated over the years, pyogenic infections due to <em>Staphylococcus aureus</em> seems to be uprising. Paravertebral abscess and neurological impairment are important dyscitis complications, especially in tuberculous cases.<br /><strong>Conclusion:</strong> Spinal infections requiring surgical treatment are still an important clinical condition. <em>Mycobacterium tuberculosis</em> and <em>Staphylococcus aureus</em> represent the main pathogens with a growing incidence for the latest.</p>


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