High Rates Of Antibiotic Resistance Research Articles

Ameliorating Gonorrhea: Recent Therapeutic Adaptations and Scope to Improve its Prevailing Condition.

Gonorrhea is a sexually transmitted infection (STI) caused by the bacteria Neisseria gonorrhoeae. According to recent research, the prevalence of gonorrhea has been increasing in many parts of the world, with some areas reporting high rates of antibiotic resistance. In the United States, the Centers for Disease Control and Prevention (CDC) reported that the number of reported gonorrhea cases increased by 56% between 2015 and 2019. Globally, the World Health Organization (WHO) estimated that there were 87 million new cases of gonorrhea in 2016, with the highest burden of infection in low- and middle-income countries. Research has also shown that gonorrhea is becoming increasingly resistant to conventional antibiotics, increasing the prevalence of gonorrhea. This raises concerns and challenges in disease management. The present review gives updated insight on the current state of the disease, challenges, and shortcomings of existing approaches along with the modern and alternative direction like vaccine development, its challenges, and scope to confront the existing state of drug resistance and increased rate of incidence. Alternative strategies like immunotherapy and phage therapy along with recent antibiotics researched for the treatment of gonorrhea. The review provides a thorough insight into the current state of the disease and various available methods used currently and recommended by WHO. To overcome disease prevalence, various alternate therapies are coming into the limelight. However, scientists and researchers show a lack of interest in the drug development and research of gonorrhea, due to less commercial scope, lack of funding, and limited scope in the scientific scenario. These hurdles need to be overcome to meet the WHO vision of reducing gonorrhea by 90% by 2030. So, there is a need to optimize the drug therapy (optimizing dosing schedule, and precision monitoring) to reduce the chance of drug resistance. Also, there is a wide scope for drug and therapeutic system development.

Prevalence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Associated Clinical Implications at the University Teaching Hospital of Kigali in Rwanda.

Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae poses a global problem and complicates therapeutic choices. The paucity of data in resource-poor countries undermines the understanding of the problem's extent, and cases of antimicrobial treatment failure continue to accumulate. This study aimed to determine the prevalence and clinical implications of ESBL-producers at the University Teaching Hospital of Kigali in Rwanda. A 1-year cross-sectional retrospective study was conducted on Escherichia coli and Klebsiella pneumoniae isolated in blood and urine from January 1 to December 31, 2022. In total, 1,283 isolates were recorded. The results showed an overall prevalence of ESBL phenotypes at 300/1,283 (23.4%). Extended spectrum beta-lactamase-positive E. coli was more frequently detected than K. pneumoniae in both urine (20.6% versus 10.1%) and blood (8.8% versus 6.2%). These isolates were 100% resistant to amoxicillin-clavulanic acid, third-generation cephalosporins, piperacillin, sulbactam ampicillin, ampicillin, cefuroxime, and cefoxitin. The least resistance was observed to amikacin (18%), meropenem (10%), and polymyxin B (3%). Hospital stays ranging from 8 to 21 days were the most frequent, and the mortality rate was 10.3% in patients with ESBL cases, which was more than double the general hospital mortality rate in the same period. In conclusion, our findings indicate a high prevalence of ESBL phenotypes, high antibiotic resistance rates, prolonged hospital stays, and an increased mortality rate. These findings suggest the need for continued surveillance, planning appropriate interventions, and caution during empirical therapy.

Mycoplasma genitalium's Antibiotic Resistance in Sexually Transmitted Infections Clinics in Israel.

To determine the prevalence of antibiotic resistance rate in Mycoplasma genitalium, and distribution of mutations associated with this resistance, among patients that attended sexually transmitted infections (STI) investigation clinics. This cross-sectional study included M. genitalium-positive samples (urine, vaginal, rectal, and pharyngeal swabs) collected from 170 patients attending two STI investigation clinics, which were subjected to macrolide and quinolone resistance mutations analyses. Data regarding patient age, sex, and material/anatomical site of testing were collected. Macrolide-resistance mutations were identified in 48.8% of samples and were more common among males (p < .0001) and in rectal samples (p < .05). A2059C was the most prevalent macrolide-resistance mutation (18.2%). Quinolone resistance was detected in 23% of the samples, with S83I being the most common (17.1%) mutation. Rate of co-resistance to macrolides and quinolones was 21.2%. The high rate of antibiotic resistance found in the current study, especially to macrolides, underscores the importance of antibiotic resistance monitoring in M. genitalium isolates in cases of persistent or recurrent urethritis/cervicitis, in cases of treatment failure and among specific populations. Such surveillance will improve treatment regimens and cure rates.

Revealing roles of S-layer protein (SlpA) in Clostridioides difficile pathogenicity by generating the first slpA gene deletion mutant.

Clostridioides difficile infection (CDI) with high morbidity and high mortality is an urgent threat to public health, and C. difficile pathogenesis studies are eagerly required for CDI therapy. The major surface layer protein, SlpA, was supposed to play a key role in C. difficile pathogenesis; however, a lack of isogenic slpA mutants has greatly hampered analysis of SlpA functions. In this study, the whole slpA gene was successfully deleted for the first time via CRISPR-Cas9 system. Deletion of slpA in C. difficile resulted in smaller, smother-edged colonies, shorter bacterial cell size, and aggregation in suspension. For life cycle, the mutant demonstrated lower growth (changes of optical density at 600 nm, OD600) but higher cell density (colony-forming unit, CFU), decreased toxins production, and inhibited sporulation. Moreover, the mutant was more impaired in motility, more sensitive to vancomycin and Triton X-100-induced autolysis, releasing more lactate dehydrogenase. In addition, SlpA deficiency led to robust biofilm formation but weak adhesion to human host cells.IMPORTANCEClostridioides difficile infection (CDI) has been the most common hospital-acquired infection, with a high rate of antibiotic resistance and recurrence incidences, become a debilitating public health threat. It is urgently needed to study C. difficile pathogenesis for developing efficient strategies as CDI therapy. SlpA was indicated to play a key role in C. difficile pathogenesis. However, analysis of SlpA functions was hampered due to lack of isogenic slpA mutants. Surprisingly, the first slpA deletion C. difficile strain was generated in this study via CRISPR-Cas9, further negating the previous thought about slpA being essential. Results in this study will provide direct proof for roles of SlpA in C. difficile pathogenesis, which will facilitate future investigations for new targets as vaccines, new therapeutic agents, and intervention strategies in combating CDI.

Monitoring and Outcomes of Central Line-Associated Bloodstream Infections in a Tertiary Care Intensive Care Unit.

Background Central line-associated bloodstream infections (CLABSIs) are significant healthcare-associated infections that increase morbidity, mortality, and healthcare costs. This study aims to analyze the frequency, microbiology, risk factors, and outcomes of CLABSI in an adult intensive care unit. Methods We conducted a hospital-based, prospective surveillance study in the critical care unit of a tertiary care hospital. We included patients with a central line (CL) from admission until discharge or line removal. Data collection focused on patient demographics, comorbidities, CL insertion site, and CLABSI rates. The incidence of CLABSI was calculated per 1,000 CL-days, and statistical analysis was performed using the Chi-square test. Results Of the 169 patients enrolled, 123 episodes of bloodstream infections were recorded, 56 (45.5%) of which were CLABSIs. The organisms most frequently isolated were Klebsiella pneumoniae (n = 14; 24.6%), Enterobacter cloacae complex (n = 11; 19.3%), Klebsiella species (n = 7; 12.28%), and Acinetobacter baumannii (n = 7; 12.28%). The overall CLABSI rate was 24.70 per 1,000 CL-days. No significant association was found between CLABSI and patient age, gender, or the site of CL insertion. However, a significant relationship was observed between CLABSI and the presence of comorbid conditions (p = 0.001). The study also noted a high rate of antibiotic resistance among the isolated pathogens. Conclusions Our results emphasize the need for stringent infection control measures and suggest that comorbid conditions significantly increase the risk of CLABSI. Addressing antibiotic resistance and implementing effective prevention strategies are essential for reducing the burden of CLABSIs.

In vitro assessment of newer colistin-sparing antimicrobial agents for clinical isolates of carbapenem-resistant organisms

ObjectivesCarbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs. MethodsA prospective study conducted at a tertiary care hospital in India during 2021–23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR. ResultsDuring the study period, predominantly (70 %) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1% to 79 %. Majority of the carbapenemase producers were metallo-β-lactamases (MBL) producers (75 %). Colistin resistance was noted in 5.4 % of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0–14 %), while resistance to newer β-lactam/β-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer β-lactam/β-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region. ConclusionThe escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance.

Prevalence and Antimicrobial Resistance Diversity of Salmonella Isolates in Jiaxing City, China.

Nontyphoidal Salmonella (NTS) is a cause of foodborne diarrheal diseases worldwide. Important emerging NTS serotypes that have spread as multidrug-resistant high-risk clones include S. Typhimurium monophasic variant and S. Kentucky. In this study, we isolated Salmonella in 5019 stool samples collected from patients with clinical diarrhea and 484 food samples. Antibiotic susceptibility testing and whole-genome sequencing were performed on positive strains. The detection rates of Salmonella among patients with diarrhea and food samples were 4.0% (200/5019) and 3.1% (15/484), respectively. These 215 Salmonella isolates comprised five main serotypes, namely S. Typhimurium monophasic variant, S. Typhimurium, S. London, S. Enteritidis, and S. Rissen, and were mainly resistant to ampicillin, tetracycline, chloramphenicol, and trimethoprim/sulfamethoxazole. The MDR rates of five major serotypes were 77.4%, 56.0%, 66.7%, 53.3%, and 80.0%, respectively. The most commonly acquired extended-spectrum β-lactamase-encoding genes were blaTEM-1B, blaOXA-10, and blaCTX-M-65. The S. Typhimurium monophasic variant strains from Jiaxing City belonged to a unique clone with broad antibiotic resistance. S. Kentucky isolates showed the highest drug resistance, and all were MDR strains. The discovery of high antibiotic resistance rates in this common foodborne pathogen is a growing concern; therefore, ongoing surveillance is crucial to effectively monitor this pathogen.

Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.

The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence. 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), respectively. We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

A situational analysis of antibiotic prescription, dispensing practices and resistance pattern in Nepal: Are we losing the battle?

Background: Antibiotics are widely utilized to treat infections and provide preventative and therapeutic benefits in animal and human healthcare. However, because of the emergence and spread of resistance mechanisms, which cause bacteria to become less susceptible to antibiotics and other treatments and less effective, antimicrobial resistance (AMR) has grown to be one of the most significant worldwide public health concerns. Low- and middle-income countries (LMICs) such as Nepal have a high rate of infectious illnesses and antibiotic resistance, which can lead to both human and financial losses. Methods: The information for the scenario analysis was acquired through a review of published and grey literature, as well as interviews with important stakeholders from all sectors. Conclusion: Besides knowing all the challenges of antibiotic resistance, the programs assuring towards AMR is conducted in Nepal in very infrequent way. The antibiotic use should be optimize by giving various personalized treatment approaches and accurate diagnosis which plays vital roles in minimizing unnecessary antibiotic prescriptions. We can organize different awareness programs to reduce antibiotic resistance that may enhance the proper use of antibiotic with proper dose and prescription in accordance health care professionals. Interpreting all the problems, government should give more priority to antibiotic resistance and should be able to minimize the problems. If antibiotic resistance is not taken in a very serious way by all the healthcare workers like doctors, nurses, pharmacists, lab technicians, etc. then the battle we are fighting leads to be defeated and problem will never end.

Should we review our prophylaxis approach for increased antibiotic resistance in transrectal prostate biopsy?

This study aims to show the bacteriologic picture of acute prostatitis and bacteremia caused by infective agent after transrectal ultrasound-guided prostate biopsy (TRUSBx) and to determine the resistance rates of the infections in patients undergoing transrectal biopsy and to guide prophylaxis approach before biopsy. The retrospective data of 935 patients who underwent TRUSBx between January 2010 to January 2019 were reviewed. Pre-biopsy urine cultures and antimicrobial susceptibility were obtained. Subsequently, patients admitted to the hospital with any complaint after biopsy were examined for severe infection complications. Of the 430 (61.7%) patients who underwent urine culture before the procedure, 45 (10.5%) had growth; 30 (66.7%) of the growing microorganisms were Escherichia coli. Twenty (44.4%) of all Gram-negative agents in pre-biopsy urine culture were susceptible to quinolone. Post TRUSBx bacteremia was present in 18.2%, urinary system infection in 83.6%, and hospitalization in 61.8% of 55 patients who were admitted to the hospital. In the isolated gram-negative microorganisms, fluoroquinolones resistance in urinary system infections was seen in 40% and bacteremia was seen in 70% of the cases. ESBL-producing Gram-negative bacteria were determined in 40% of infections in blood and 38.5% of urinary system infections in the post biopsy period in the current study. These high antibiotic resistance rates suggest that we better review our pre-procedure prophylaxis approaches.

Risk factors for bacteremic pneumonia and mortality (28-day mortality) in patients with Acinetobacter baumannii bacteremia

BackgroundPatients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs.MethodsA retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group.ResultsAmong 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098–0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008–0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930–0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105–0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia.ConclusionsOur study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia.

Comparison of the Efficacy of 12-day Concomitant Quadruple Therapy versus 14-day High dose Dual Therapy as a First-line H. pylori Eradication Regimen.

Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.

High prevalence of plasmid-mediated quinolone resistance in escherichia coli strains producing extended-spectrum beta-lactamases isolated from faeces and urine of pregnant women with acute cystitis.

Escherichia coli is the most common etiological agent of urinary tract infections (UTIs). Meanwhile, plasmid-mediated quinolone resistance (PMQR) is reported in E. coli isolates producing extended-spectrum β-lactamases (ESBLs). Furthermore, the reservoirs and mechanisms of acquisition of uropathogenic Escherichia coli (UPEC) strains are poorly understood. On the other hand, UTIs are common in pregnant women and the treatment challenge is alarming. In the present study, 54 pregnant women with acute cystitis were included. A total of 108 E. coli isolates, 54 isolates from UTI and 54 isolates from faeces of pregnant women (same host) were collected. In the antimicrobial susceptibility test, the highest rate of antibiotic resistance was to nalidixic acid (77%, 83/108) and the lowest rate was to imipenem (9%, 10/108). Among the isolates, 44% (48/108) were ESBLs producers. A high frequency of PMQR genes was observed in the isolates. The frequency of PMQR genes qnrS, qnrB, aac(6')-Ib-cr, and qnrA was 58% (63/108), 21% (23/108), 9% (10/108), and 4% (4/108), respectively. Meanwhile, PMQR genes were not detected in 24% (20/85) of isolates resistant to nalidixic acid and/or fluoroquinolone, indicating that other mechanisms, i.e. chromosomal mutations, are involved in resistance to quinolones, which were not detected in the present study. In ESBL-producing isolates, the frequency of PMQR genes was higher than that of non-ESBL-producing isolates (81% vs. 53%). Meanwhile, UTI and faeces isolates mainly belonged to phylogenetic group B2 (36/54, 67% and 25/54, 46%, respectively) compared to other phylogenetic groups. In addition, virulence factors and multidrug-resistant (MDR) were mainly associated with phylogenetic group B2. However, predominant clones in faeces were not found in UTIs. Rep-PCR revealed the presence of 85 clones in patients. Among the clones, 40 clones were detected only in faeces (faeces-only), 35 clones only in UTI (UTI-only) and 10 clones in both faeces and UTI (faeces-UTI). We found that out of 10 faeces-UTI clones, 5 clones were present in the host's faeces flora. This study revealed a high rate of resistance to the quinolone nalidixic acid and a widespread distribution of PMQR genes in MDR E. coli strains producing ESBLs. The strains represented virulence factors and phylogenetic group B2 are closely associated with abundance in UTI and faeces. However, the predominant clones in faeces were not found in UTIs and it is possible that rep-PCR is not sufficiently discriminating clones.

Bacteriological Evaluation of Surface and Groundwater used for Domestic Purposes in Ibadan

The right to safe and clean drinking water is a human right, unfortunately many communities rely on unsafe and contaminated water for drinking and domestic purposes. Through improper sewage and hospital waste disposal, pathogenic and antibiotic resistant bacteria have found their way to natural water sources used by humans. In this study we aim to profile pathogenic bacteria and resistant Escherichia coli (E. coli) from surface and ground water sources in three local government areas of Oyo state. 30 water samples were collected randomly from the selected local government areas. Bacteriological, biochemical and antibiotic-resistant analysis was carried out on the isolated bacteria from the water samples. E. coli (28.30%) and Kleb pneumoniae (23.77%) were the predominant bacteria isolates, while Shigella (16.22%) and Salmonella (16.22%) also had substantial percentages. Nineteen E. coli was isolated and identified, with high antibiotic resistance rates observed in nalidixic Acid (100%), augmentin (100%), ampiclox (94.74%) and third-generation cephalosporins. Conversely, moderate levels of resistance were observed in nitrofurantoin (55.55%), cefepime (57.89%), and second-generation fluoroquinolones. This study reveals substantial pathogenic bacteria and antibiotic resistant E. coli in water samples which endangers the health of communities’ dependent on these water sources and exposes the inhabitants to antibiotic-resistant organisms from contaminated water used for domestic purposes. It is crucial to put in place water treatment measures and quality monitoring programmes in order to guarantee that the populace has access to clean and safe drinking water.

Extended spectrum beta-lactamase production and blaCTX-M gene in Escherichia coli and Klebsiella pneumoniae causing urinary tract infection at a tertiary care hospital in Nepal

Background and objective: Urinary tract infections (UTIs) are the most common bacterial infections where Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the predominating pathogens. These pathogens have a high rate of antibiotic resistance and exhibit the production of extended-spectrum beta-lactamase (ESBL). This study investigated the antibiotic resistance pattern and ESBL production of E. coli and K. pneumoniae isolated from patients with UTIs attending a tertiary care hospital in Nepal by both phenotypic and genotypic techniques. Materials and methods: A cross-sectional study was performed where 4664 mid-stream urine specimens from suspected UTI cases were cultured. Isolated E. coli and K. pneumoniae were subjected to antibiotic susceptibility testing by Kirby Bauer disc diffusion method. Genotypic detection of blaCTX-M gene was performed using polymerase chain reaction (PCR). Results: Out of 4664 urine samples processed, 564 (12.1%) were positive for E. coli (475, 10.2%) and K. pneumonia (89, 1.9%). Out of the total 564 studied samples, 267 (47.3%) were MDR isolates (E. coli: 222, 46.7%; K. pneumoniae: 45, 50.6%) and 96 (17%) were positive for ESBL by double disc confirmatory test. Out of 24 ESBL positive E. coli and 6 K. pneumoniae, 19 (79.2%) and 3 (50%) respectively were positive for blaCTX-M gene. Conclusion: This study indicates high prevalence of MDR and ESBL producing E. coli and K. pneumoniae causing UTIs at an urban hospital setting in Nepal. July 2024; Vol. 18(2):002. DOI: https://doi.org/10.55010/imcjms.18.014 *Correspondence: Gaurab Pandey, Department of Medical Laboratory Science, Nobel College Affiliated to Pokhara University, Kathmandu, Nepal. Email: pandeygaurab67@gmail.com

Computational approach for identifying immunogenic epitopes and optimizing peptide vaccine through in-silico cloning against Mycoplasma genitalium

Mycoplasma genitalium is a pathogenic microorganism linked to a variety of severe health conditions including ovarian cancer, prostate cancer, HIV transmission, and sexually transmitted diseases. A more effective approach to address the challenges posed by this pathogen, given its high antibiotic resistance rates, could be the development of a peptide vaccine. In this study, we used experimentally validated 13 membrane proteins and their immunogenicity to identify suitable vaccine candidates. Thus, based on immunogenic properties and high conservation among other Mycoplasma genitalium sub-strains, the P110 surface protein is considered for further investigation. Later on, we identified T-cell epitopes and B-cell epitopes from the P110 protein to construct a multiepitope-based vaccine. As a result, the ‘NIAPISFSFTPFTAA’ T-cell epitope and ‘KVKYESSGSNNISFDS’ B-cell epitope have shown 99.53% and 87.50% population coverage along with 100% conservancy among the subspecies, and both epitopes were found to be non-allergenic. Furthermore, focusing on molecular docking analysis showed the lowest binding energy for MHC-I (−137.5 kcal/mol) and MHC-II (−183.3 kcal/mol), leading to a satisfactory binding strength between the T-cell epitopes and the MHC molecules. However, the constructed multiepitope vaccine (MEV) consisting of 54 amino acids demonstrates favorable characteristics for a vaccine candidate, including a theoretical pI of 4.25 with a scaled solubility of 0.812 and high antigenicity probabilities. Additionally, structural analyses reveal that the MEV displays substantial alpha helices and extended strands, vital for its immunogenicity. Molecular docking with the human Toll-like receptors TLR1/2 heterodimer shows strong binding affinity, reinforcing its potential to elicit an immune response. Our immune simulation analysis demonstrates immune memory development and robust immunity, while codon adaptation suggests optimal expression in E. coli using the pET-28a(+) vector. These findings collectively highlight the MEV's potential as a valuable vaccine candidate against M. genitalium.

High antibiotic resistance rates in Helicobacter pylori strains in Turkey over 20 years: implications for gastric disease treatment.

Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

Prevalence of Streptococcus agalactiae in Urinary Tract Infections of Pregnant Women

Background: Urinary tract infection is the most common bacterial infection in children and adults, especially females. Among urinary tract infection caused by bacteria, Streptococcus agalactiae can cause periodic, temporary, or persistent infection in women. The aim of this study was to evaluate the prevalence of S. agalactiae isolated from urine samples in pregnant women referred to Qom hospitals, Iran.&#x0D; Methods: In this descriptive study, 1264 pregnant women suspected for urinary tract infection were assessed. Midstream urine specimens collected from pregnant individuals in Ali-ibn-AbiTaleb hospital medical laboratory were passaged on blood agar media. Streptococcus agalactiae was detected using phenotype-based tests. Then, antibiotic susceptibility tests were conducted using the disc diffusion method according to CLSI protocols.&#x0D; Results: Out of 1264 pregnant patients, 17.64% were diagnosed with beta-hemolytic Streptococcus, and 13.37% were diagnosed with S. agalactiae. The highest rates of antibiotic resistance were found for Clindamycin and Erythromycin. In place, the lowest resistance rate was detected for Nitrofurantoin. The prevalence of resistance to Penicillin was about 33%.&#x0D; Conclusion: Regarding the results of this research, it would be better to perform urine culture tests before week 34 of pregnancy and the last weeks of pregnancy. Also, our results showed that Penicillin can be replaced by alternative antibiotics before week 34 of pregnancy to prevent further S. agalactiae antibiotic resistance.

Phylogenetic analysis, biofilm formation, antimicrobial resistance and relationship between these characteristics in Uropathogenic Escherichia coli.

In the present study, we examine the prevalence of phylogenetic groups, O-serogroups, adhesin genes, antimicrobial resistance, the level of gene expression associated with biofilm formation, and the presence of extended-spectrum beta-lactamase (ESBL) in UPEC strains isolated from both pediatric and adult patients. In this cross-sectional study, 156 UPEC isolates were collected from UTI patients. ESBL-producing isolates were detected using the double-disc synergy (DDS) method, and biofilm formation was assessed through a microplate assay. The presence of O-serogroups, adhesion factors and resistance genes, including ESBLs and PMQR genes, was detected by PCR, and isolates were categorized into phylogenetic groups using multiplex PCR. Additionally, the quantitative real-time PCR method was also used to determine the expression level of genes related to biofilm. During the study period, 50.6% (79/156) of the samples were obtained from children, and 49.4% (77/156) were from adults. The highest rate of resistance was to NA (91.7%), while FM (10.9%) had the lowest rate of antibiotic resistance. In addition, 67.9% (106/156) of UPEC isolates were ESBL producers. Most of UPEC isolates belonged to phylogenetic group B2 (37.1%). This study revealed that blaCTX-M and qnrS are widely distributed among UPEC isolates. The mean expression levels of fimA genes were significantly higher in non-biofilm producers than in biofilm producers (p < 0.01). The high antibiotic resistance rates in this study highlight the significance of local resistance monitoring and investigating underlying mechanisms. Our findings indicate the dominance of phylogroup B2 and group D as the prevailing phylogenetic groups. Consequently, it is imperative to investigate the epidemiological aspects and characterize UPEC isolates across diverse regions and time frames.

Real-world utilization of ceftazidime/avibactam among inpatients in the national Veterans Affairs Healthcare System.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture site.