scholarly journals Drug Reprofiling: In Silico Modelling of Haemophilus Influenzae Disease, Staphylococcus aureus Related Pneumonia and Urinary Tract Infections

Author(s):  
Bharat Kwatra ◽  
Amarthya Siddhartha ◽  
Deepa Suryanarayan ◽  
Shryli Kedambadi Shreekar

According to reports of ReAct forum, every year more than 750,000 patients die due to bacterial infections, making bacterial infection one of the leading causes of disease infestation in an individual. Haemophilus influenzae disease, pneumonia and urinary tract infections make the top of this list. Haemophilus influenzae is a gram-negative, commensal, facultative bacterium, which can mostly cause pneumonia along with other diseases including bloodstream infections and arthritis. Though vaccine exists for Hib infections, during infections of Hib and NThi the patients are administered antibiotics to treat the disease. Staphylococcus aureus is a grampositive versatile bacterium of the micrococcaceae family and one of the most dangerous pathogen-affecting humans as it can cause pneumonia. Pneumonia is an acute pulmonary infection, which is associated with high mortality having a more pronounced effect on young children. Urinary Tract Infection is a prevalent public health problem that is more common in women than in men. Though it can be treated by appropriate antibiotics, due to recurrent infections, they lead to a gain of resistance. Thousands of research are going on around the world to come up with a potential drug that can cure the Hi disease, Staphylococcus aureus related pneumonia and UTIs entirely with the least drawbacks. In this study, we present a docking-based screening using a quantum mechanical scoring of a library built from approved drugs and compounds, Amoxicillin and Cefuroxime with proteins with PDB ids 3CKM, 3EMF, 3ZU0, 4MV9, 5KCN, 5VBG, and 6XXY for Hi disease, 4RBR, 4MVN, 3KOR and 2RKZ for Staphylococcus aureus related pneumonia and 6QVX, 2F00, 6AYI and 2ID0 for UTIs could display antibacterial activity against the respective bacterial infections. This study needs to be evaluated and further confirmed through experimental assays and clinical trials to validate the predicted results. This finding aims to provide a better understanding and contribute

2020 ◽  
Vol 41 (S1) ◽  
pp. s73-s74
Author(s):  
Wendi Gornick ◽  
Beth Huff ◽  
Jasjit Singh

Background: Central-line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) definitions continue to be refined to ensure accuracy. As facilities decrease CLABSI and CAUTI, and as midline catheters become more widely utilized, we sought to understand our non–central-line bloodstream infections (NCLBSI) and non–catheter-associated urinary tract infections (NCAUTI). Total healthcare-associated bloodstream infections (HABSIs) and urinary tract infections (HAUTIs) may provide more objective measures. Methods: The CHOC Children’s Hospital is a 334-bed quaternary-care hospital in Orange, California, with 146 intensive care unit (ICU) beds. We retrospectively reviewed all HABSIs (CLABSIs + NCLBSIs) and HAUTIs (CAUTIs + NCAUTIs) from July 1, 2016, to June 30, 2019, for demographic and microbiologic data. Both HABSI and HAUTI were defined as healthcare-associated infection when the date of event occurs on or after the third calendar day of admission. CLABSI and CAUTI were both defined using CDC-NHSN criteria. Mucosal barrier injury laboratory-confirmed bloodstream infections were excluded. Results: In a 3-year period, there were 100 HABSIs, of which 26 (26%) were NCLBSIs. The mean age for HABSI was 81 months. Enteric gram-negative infections (42%) and Staphylococcus aureus (35%) were the most common etiology for NCLBSI. The most common etiologies for CLABSI were coagulase-negative staphylococci (23%), Staphylococcus aureus (22%), and enteric gram-negatives (22%). Pseudomonas aeruginosa accounted for 16% of CLABSIs, but no NCLBSIs (Fig. 1). There was 1 midline catheter NCLBSI. There were 49 HAUTIs, of which 39 (80%) were NCAUTIs. One asymptomatic bacteremic urinary tract infection was included with the CAUTIs. The mean age for HAUTI was 55 months. The most common etiology of CAUTI was Pseudomonas aeruginosa (50%), whereas for NCAUTI the most common etiology was enteric gram-negative organisms (69%) (Fig. 2). In total, 11 HAUTIs (22%) resulted in secondary sepsis. Most HABSIs and HAUTIs occurred in the ICU setting. There were 6 deaths (6%) among HABSI patients and 3 deaths (8%) among HAUTI patients within 2 weeks of infection (Fig. 3). Conclusions: A preponderance of HABSIs were CLABSIs, but most HAUTIs were NCAUTIs. Although patient demographic and microbiologic differences exist in CLABSIs and NCLBSIs as well as CAUTIs and NCAUTIs, S. aureus and P. aeruginosa are important pathogens, particularly in device-associated infections. Trending total numbers of HABSIs and HAUTIs may be less subjective and may avert the shifting of categories seen with increased use of midline catheters. In addition, non–device-associated infections are potential causes of morbidity and mortality.Funding: NoneDisclosures: None


2001 ◽  
Vol 45 (12) ◽  
pp. 3524-3530 ◽  
Author(s):  
Christoph K. Naber ◽  
Michaela Hammer ◽  
Martina Kinzig-Schippers ◽  
Christian Sauber ◽  
Fritz Sörgel ◽  
...  

ABSTRACT In a randomized crossover study, 16 volunteers (8 men, 8 women) received single oral doses of 320 mg of gemifloxacin and 400 mg of ofloxacin on two separate occasions in the fasting state to assess the urinary excretion and urinary bactericidal titers (UBTs) at intervals for up to 144 h. Ofloxacin showed higher concentrations in urine compared with those of gemifloxacin. The median (range) cumulative excretion of gemifloxacin was 29.7% (8.4 to 48.7%) of the parent drug administered, and median (range) cumulative excretion of ofloxacin was 84.3% (46.5 to 95.2%) of the parent drug administered. The UBTs, i.e., the highest twofold dilutions (with antibiotic-free urine as the diluent) of urine that were still bactericidal, were determined for a reference strain and nine uropathogens for which the MICs of gemifloxacin and ofloxacin were as follows:Escherichia coli ATCC 25922, 0.016 and 0.06 μg/ml, respectively; Klebsiella pneumoniae, 0.03 and 0.06 μg/ml, respectively; Proteus mirabilis, 0.125 and 0.125 μg/ml, respectively; Escherichia coli, 0.06 and 0.5 μg/ml, respectively; Pseudomonas aeruginosa, 1 and 4 μg/ml, respectively; Staphylococcus aureus, 0.008 and 0.25 μg/ml, respectively; Enterococcus faecalis, 0.06 and 2 μg/ml, respectively;Staphylococcus aureus, 0.25 and 4 μg/ml, respectively;Enterococcus faecalis, 0.5 and 32 μg/ml, respectively; and Staphylococcus aureus, 2 and 32 μg/ml, respectively. Generally, the UBTs for gram-positive uropathogens were higher for gemifloxacin than for ofloxacin and the UBTs for gram-negative uropathogens were higher for ofloxacin than for gemifloxacin. According to the UBTs, ofloxacin-resistant uropathogens (MICs, ≥4 mg/liter) should also be considered gemifloxacin resistant. Although clinical trials have shown that gemifloxacin is effective for the treatment of uncomplicated urinary tract infections, whether an oral dosage of 320 mg of gemifloxacin once daily is also adequate for the treatment of complicated urinary tract infections has yet to be confirmed.


Author(s):  
Jongsoon Won ◽  
Kyunghee Kim ◽  
Kyeong-Yae Sohng ◽  
Sung-Ok Chang ◽  
Seung-Kyo Chaung ◽  
...  

Background: Many countries around the world are currently threatened by the COVID-19 pandemic, and nurses are facing increasing responsibilities and work demands related to infection control. To establish a developmental strategy for infection control, it is important to analyze, understand, or visualize the accumulated data gathered from research in the field of nursing. Methods: A total of 4854 articles published between 1978 and 2017 were retrieved from the Web of Science. Abstracts from these articles were extracted, and network analysis was conducted using the semantic network module. Results: ‘wound’, ‘injury’, ‘breast’, “dressing”, ‘temperature’, ‘drainage’, ‘diabetes’, ‘abscess’, and ‘cleaning’ were identified as the keywords with high values of degree centrality, betweenness centrality, and closeness centrality; hence, they were determined to be influential in the network. The major topics were ‘PLWH’ (people living with HIV), ‘pregnancy’, and ‘STI’ (sexually transmitted infection). Conclusions: Diverse infection research has been conducted on the topics of blood-borne infections, sexually transmitted infections, respiratory infections, urinary tract infections, and bacterial infections. STIs (including HIV), pregnancy, and bacterial infections have been the focus of particularly intense research by nursing researchers. More research on viral infections, urinary tract infections, immune topic, and hospital-acquired infections will be needed.


Author(s):  
Santosh Paudel ◽  
Kamal Bagale ◽  
Swapnil Patel ◽  
Nicholas J. Kooyers ◽  
Ritwij Kulkarni

Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains to human urine for 2h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep RBCs, and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, RNA-Seq analysis of uropathogenic strain MRSA-1369 revealed that 2h-long exposure to human urine alters MRSA transcriptome, by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. Importance: Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA-UTI.


2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S16-S16
Author(s):  
Sara Kim ◽  
Avni Bhatt ◽  
Silvana Carr ◽  
Frances Saccoccio ◽  
Judy Lew

Abstract Background Procalcitonin (PCT) and c-reactive protein (CRP) have been utilized in children to assess risk for serious bacterial infections. However, there have been different cut-offs reported for PCT and CRP, which yield different sensitivity and specificity. This study aims to compare the sensitivity and specificity of PCT and CRP in detecting serious bacterial infections (SBIs), specifically urinary tract infections, bacteremia and meningitis. Methods In this retrospective, single center cohort study from January 2018 to June 2019, we analyzed children with a fever greater than 38C with both PCT and CRP value within 24 hours of admission. Each patient had a blood, urine and/or cerebrospinal fluid culture collected within 48 hours of admission. No antibiotics were administered from the admitting hospital prior to collection of the PCT or CRP. Our gold standard was a positive culture obtained from blood, cerebrospinal fluid, or urine. The statistical analysis included categorical variables as percentages and compared them using the Fisher exact test. The optimal cutoff values for PCT or CRP were based on ROC curve analysis and Youden Index. Sensitivity and specificity analysis were based on literature review cut offs and ROC curves cut offs. Results Among 202 children, we had 45 culture positive patients (11 urinary tract infections, 4 meningitis, and 32 bacteremia). The patients with culture positivity had higher PCT levels (7.9 ng/mL vs 2.5 ng/mL, P=0.0111), CRP levels (110.9 mg/L vs 49.6 mg/L, P<0.0001) and temperature (39.2C vs 39C, P<0.0052). The area under the curve (AUC) comparing culture positivity vs negativity for all culture types was 0.72 (p<0.0001) for PCT and 0.66 (p=0.001) for CRP. In Figure 1, the AUC for culture positive bacteremia was 0.68 (p=0.0011) for PCT and 0.70 (p=0.0003). The AUC for culture positive urinary tract infections (UTI) only was 0.86 (p=0.0001) for PCT and 0.70 (p=0.3607). For the cut-off value for PCT at 0.5 ng/mL, the sensitivity and specificity was 64% (95% confidence interval [CI] 0.5–0.77) and 70% (95% CI 0.62–0.77) respectively in identifying children with bacterial infection. For the cut-off value for CRP at 20 mg/L, the sensitivity and specificity was 67% (95% CI 0.52–0.79) and 52% (95% CI 0.44–0.59) respectively in identifying children with bacterial infection. Conclusion In this study, PCT and CRP are nearly equivalent classifiers for detecting SBIs as a group and bacteremia, but PCT is statistically better for urinary tract infections; however, the clinical utility is unknown.


2021 ◽  
Vol 12 (3) ◽  
pp. 1740-1744
Author(s):  
Eva Lorel Kouassi ◽  
Abdul Wahid Ishaque ◽  
Amulya P. Shetty ◽  
Rimpa Devi ◽  
Sheethal Kuriakose ◽  
...  

Although urinary tract infections (UTIs) are considered to be the most common bacterial infections worldwide, their assessment remains a big clinical challenge, because they are not reportable diseases in developed countries like United States and any other parts of the world including India. This situation is further complicated by the fact that accurate diagnosis depends on both the presence of symptoms and a positive urine culture, although in most outpatient settings this diagnosis is made without the benefit of culture. Our study aimed to appraise the impact of urinary tract infections symptoms on selected patients and comprehend their adherence to medications despite the challenges of antimicrobial susceptibility and resistance observed. One hundred and twenty patients with confirmed cases of urinary tract infections were recruited for the study. The mean age of females and males patients was found to be 59.86±2.37and 52.27±3 years respectively. Pertinent descriptive and inferential statistics were performed. Spearman correlation test revealed a strong positive correlation between overall UTIs’ symptoms and their impact on patients at baseline (0.84) and at follow up (0.799) with p value =0.5. On the other hand the majority of patients were found to be adherent to the medications after discharge. The current study revealed that Urinary tract infections if left untreated can negatively impact the lives of patients suffering from it and hinder their adherence to medications. Consequently, accurate and early assessment of UTIs’ symptoms in clinics and hospitals becomes a necessity.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Panagiota Karananou ◽  
Despoina Tramma ◽  
Socrates Katafigiotis ◽  
Anastasia Alataki ◽  
Alexandros Lambropoulos ◽  
...  

Urinary tract infections are one of the most common and serious bacterial infections in a pediatric population. So far, they have mainly been related to age, gender, ethnicity, socioeconomic level, and the presence of underlying anatomical or functional, congenital, or acquired abnormalities. Recently, both innate and adaptive immunities and their interaction in the pathogenesis and the development of UTIs have been studied. The aim of this study was to assess the role and the effect of the two most frequent polymorphisms of TLR4 Asp299Gly and Thr399Ile on the development of UTIs in infants and children of Greek origin. We studied 51 infants and children with at least one episode of acute urinary tract infection and 109 healthy infants and children. We found that 27.5% of patients and 8.26% of healthy children carried the heterozygote genotype for TLR4 Asp299Gly. TLR4 Thr399Ile polymorphism was found to be higher in healthy children and lower in the patient group. No homozygosity for both studied polymorphisms was detected in our patients. In the group of healthy children, a homozygote genotype for TLR4 Asp299Gly (G/G) as well as for TLR4 Thr399Ile (T/T) was showed (1.84% and 0.92 respectively). These results indicate the role of TLR4 polymorphism as a genetic risk for the development of UTIs in infants and children of Greek origin.


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