Multiple Antibiotics Research Articles

A Novel Dhillonvirus Phage against Escherichia coli Bearing a Unique Gene of Intergeneric Origin.

Antibiotics resistance is expanding amongst pathogenic bacteria. Phage therapy is a revived concept for targeting bacteria with multiple antibiotics resistances. In the present study, we isolated and characterized a novel phage from hospital treatment plant input, using Escherichia coli (E. coli) as host bacterium. Phage lytic activity was detected by using soft agar assay. Whole-genome sequencing of the phage was performed by using Next-Generation Sequencing (NGS). Host range was determined using other species of bacteria and representative genogroups of E. coli. Whole-genome sequencing of the phage revealed that Escherichia phage Ioannina is a novel phage within the Dhillonvirus genus, but significantly diverged from other Dhillonviruses. Its genome is a 45,270 bp linear double-stranded DNA molecule that encodes 61 coding sequences (CDSs). The coding sequence of CDS28, a putative tail fiber protein, presented higher similarity to representatives of other phage families, signifying a possible recombination event. Escherichia phage Ioannina lytic activity was broad amongst the E. coli genogroups of clinical and environmental origin with multiple resistances. This phage may present in the future an important therapeutic tool against bacterial strains with multiple antibiotic resistances.

Antimicrobial resistance characterization of Enterococcus faecium, Enterococcus faecalis and Enterococcus hirae isolated from marine coastal recreational waters in the State of São Paulo, Brazil.

Coastal water quality is facing increasing threats due to human activities. Their contamination by sewage discharges poses significant risks to the environment and public health. We aimed to investigate the presence of antibiotic-resistant Enterococcus in beach waters. Over a 10-month period, samples were collected from four beaches in the State of São Paulo (Brazil). Enterococcus isolates underwent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) and molecular analysis for accurate genus and species identification. The antimicrobial susceptibility for 14 antibiotics was evaluated using the disc diffusion method followed by a multidrug-resistance (MDR) classification. PCR amplification method was used to detect antimicrobial resistance genes (ARGs). Our findings revealed the prevalence of Enterococcus faecalis, E. faecium and E. hirae. Out of 130 isolates, 118 were resistant to multiple antibiotics. The detection of resistance genes provided evidence of the potential transfer of antibiotic resistance within the environment. Our findings underscore the necessity for continuous research and surveillance to enhance understanding of the pathogenicity and antimicrobial resistance mechanisms of Enterococcus, which is crucial to implement effective measures to preserve the integrity of coastal ecosystems.

A glassy carbon electrode modified with gold decorated iron oxide/ carbon dots for light assisted voltammetric detection of antibiotic resistant microbe Enterococcusfaecalis

Detecting bacteria is essential in managing significant health concerns as it enables timely intervention, reducing complications and improving patient outcomes, particularly in treating common infections that necessitate precise identification for effective symptom management. Enterococcus species represent a notable threat in hospital-acquired infections and urinary tract infections (UTIs), given the increasing prevalence of strains resistant to multiple antibiotics, unresponsive to standard therapies, and carrying various virulence factors. Traditional approaches to identifying Enterococcus faecalis (E. faecalis) have limitations, including prolonged processing times, limited sensitivity, and the potential for false positive results. While Polymerase Chain Reaction (PCR) is a valuable tool, it is susceptible to contamination and variations in DNA concentration. The emerging technique of Photoelectrochemical (PEC) holds promise for enhancing E. faecalis detection by leveraging photogenerated electrons and holes. This study introduces a rapid and precise approach utilizing a light-assisted electrochemical biosensor featuring a glassy carbon electrode modified with a nanocomposite of gold-coated iron oxide and carbon dots (Au@Fe3O4/CDs). The nanocomposite was successfully synthesized and underwent thorough characterization. The investigation has a detection range from 1 to 14 CFU mL−1, along with a notably low limit of detection (LOD: 3 CFU mL−1, LOQ: 10 CFU mL−1). Rigorous examination of real-world samples such as food, water, and soil demonstrated exceptional specificity, reproducibility, and long-term stability of the sensor. The applications of the Au@Fe3O4/CDs nanocomposite in PEC processes underscore the potential of this innovative approach in addressing health concerns associated with bacterial infections and delivering real-time impacts for both healthcare and environmental domains.

A series of vectors for inducible gene expression in multidrug-resistant Acinetobacter baumannii.

Clinical isolates of bacterial pathogens often harbor resistance to multiple antibiotics, with Acinetobacter baumannii being a prime example. The drug-resistance phenotypes associated with these pathogens represent a significant hurdle to researchers who wish to study modern isolates due to the limited availability of plasmid tools. Here, we present a series of freely replicating and Tn7-insertion vectors that rely on selectable markers to less frequently encountered antibiotics, apramycin, and hygromycin. We demonstrate the utility of these plasmid tools through a variety of experiments looking at a multidrug-resistant strain of A. baumannii, strain AB5075. Strain AB5075 is an established model strain for present-day A. baumannii, due in part to its genetic tractability and because it is a representative isolate of the globally disseminated multidrug-resistant clade of A. baumannii, global clone 1. In addition to the drug-selection markers facilitating use in strains resistant to more commonly used antibiotics, the vectors allow for controllable expression driven by several regulatory systems, including isopropyl β-D-1-thiogalactopyranoside (IPTG), arabinose, anhydrotetracycline, and toluic acid.

In Vitro Characterization and Identification of Potential Probiotic Yeasts Isolated from Zaopocu, a Traditional Fermented Dregs Vinegar from Hainan Island.

Recently, there has been an increasing interest in researching fermented food-derived yeasts as probiotics because they offer a natural and diverse source of potential strains with unique functional properties and health benefits. In this study, 13 yeast strains isolated from Zaopocu (ZPC), a traditional fermented dregs vinegar on Hainan Island, China, were evaluated for their probiotic characteristics in vitro. Yeast identification was conducted through 5.8S-ITS region sequencing, revealing Kodamaea ohmeri as the predominantly isolated species (ZPC_Y3, Y5, Y6, Y11), followed by Pichia kudriavzevii (ZPC_Y2, Y13, Y14), Rhodotorula mucilaginosa (ZPC_Y9, Y10), Pichia fermentans (ZPC_Y8, Y12), Pichia kluyveri (ZPC_Y4), and Pichia occidentalis (ZPC_Y1). Except for ZPC_Y4, ZPC_Y8, and ZPC_Y12, all isolated yeasts exhibited stable growth at 37°C. The survival rates of all test strains exceeded 60% under challenging conditions at pH = 2 and 0.3% bile salt, along with strong antioxidant activity (> 5 6%), notable autoaggregation (> 70%), and varying levels of cell hydrophobicity with xylene (ranging from 35.32 ± 8.57% to 89.73 ± 4.84%). In addition, all isolates showed resistance to multiple antibiotics, along with antagonistic activity, and were deemed safe as none exhibited hemolytic, gelatinase, or DNase activities. Significantly, two P. kudriavzevii strains (ZPC_Y2, Y14) exhibited the production of catalase, lipase, and β-galactosidase, along with the capacity to synthesize gamma-aminobutyric acid (GABA). In summary, this preliminary study represents the first attempt to identify and characterize potential probiotic yeast strains isolated from Zaopocu, providing a theoretical basis for exploring their application in developing novel therapeutic probiotics.

Rapid determination of antibiotic susceptibility of clinical isolates of Escherichia coli by SYBR green I/Propidium iodide assay

Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.

Machine learning assisted identification of antibiotic-resistant Staphylococcus aureus strains using a paper-based ratiometric sensor array

Staphylococcus aureus, a versatile human pathogen, significantly impacts global health causing a broad spectrum of medical conditions that range from minor skin infections to life-threatening diseases. The clinical importance of S. aureus is underscored by its resistance to multiple antibiotics and formation of biofilms, providing protection against antimicrobials and immune responses. To date, the identification of antimicrobial-resistant (AMR) S. aureus strains, such as methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA), requires time-consuming and expensive methodologies, including culture-based, molecular, and phenotypic techniques. Previously, we developed a paper-based ratiometric sensor array composed of fluorescent sensor dyes (3-hydroxyflavone derivatives) pre-adsorbed on paper microzone plates. Combined with machine learning algorithms such as neural networks, this sensor effectively discriminated 16 bacterial species and determined their Gram status. In this study, we evaluate its ability to distinguish antibiotic-resistant S. aureus strains and their biofilms. Our results demonstrate that the sensor array, in conjunction with LDA and neural networks, successfully differentiated three common laboratory MRSA strains from three methicillin-susceptible S. aureus (MSSA) strains with 82.5% accuracy. Furthermore, using support vector machines, this sensor was able to distinguish and categorically classify MRSA, MSSA, and VISA clinical isolates with 97.5% accuracy. Remarkably, beyond distinguishing planktonic cultures, this sensor array demonstrated a formidable capability to discriminate AMR S. aureus biofilms, achieving over 80% accuracy. Combined, the results of this study highlight the paper-based sensor array’s significant potential as a robust diagnostic tool to accurately, rapidly, and easily identify drug-resistant S. aureus strains in clinically relevant settings.

Non-antibiotic pharmaceutical phenylbutazone binding to MexR reduces the antibiotic susceptibility of Pseudomonas aeruginosa

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P. aeruginosa against antibiotic mediated killing by binding to the efflux pump regulator MexR. In this study, antibiotic activity against P. aeruginosa alone or in combination with phenylbutazone was evaluated in vitro and in vivo. Resazurin accumulation assay, transcriptomic sequencing, and PISA assay were conducted to explore the underlying mechanism for the reduced antibiotic susceptibility caused by phenylbutazone. Then EMSA, ITC, molecular dynamic simulations, and amino acid substitutions were used to investigate the interactions between phenylbutazone and MexR. We found that phenylbutazone could reduce the susceptibility of P. aeruginosa to multiple antibiotics, including parts of β-lactams, fluoroquinolones, tetracyclines, and macrolides. Phenylbutazone could directly bind to MexR, then promote MexR dissociating from the mexA-mexR intergenic region and de-repress the expression of MexAB-OprM efflux pump. The overexpressed MexAB-OprM pump resulted in the reduced antibiotic susceptibility. And the His41 and Arg21 residues of MexR were involved in the phenylbutazone-MexR interaction. We hope this study would imply the potential risk of antibiotic resistance caused by non-antibiotic pharmaceuticals.

Epidemiology and Management of Pediatric Group A Streptococcal Pneumonia With Parapneumonic Effusion: An Observational Study.

During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.

Plant-Derived Antimicrobials and Their Crucial Role in Combating Antimicrobial Resistance.

Antibiotic resistance emerged shortly after the discovery of the first antibiotic and has remained a critical public health issue ever since. Managing antibiotic resistance in clinical settings continues to be challenging, particularly with the rise of superbugs, or bacteria resistant to multiple antibiotics, known as multidrug-resistant (MDR) bacteria. This rapid development of resistance has compelled researchers to continuously seek new antimicrobial agents to curb resistance, despite a shrinking pipeline of new drugs. Recently, the focus of antimicrobial discovery has shifted to plants, fungi, lichens, endophytes, and various marine sources, such as seaweeds, corals, and other microorganisms, due to their promising properties. For this review, an extensive search was conducted across multiple scientific databases, including PubMed, Elsevier, ResearchGate, Scopus, and Google Scholar, encompassing publications from 1929 to 2024. This review provides a concise overview of the mechanisms employed by bacteria to develop antibiotic resistance, followed by an in-depth exploration of plant secondary metabolites as a potential solution to MDR pathogens. In recent years, the interest in plant-based medicines has surged, driven by their advantageous properties. However, additional research is essential to fully understand the mechanisms of action and verify the safety of antimicrobial phytochemicals. Future prospects for enhancing the use of plant secondary metabolites in combating antibiotic-resistant pathogens will also be discussed.

Probiotic cell-free supernatant as effective antimicrobials against Klebsiella pneumoniae and reduce antibiotic resistance development.

This study evaluated the antimicrobial activity, resistance development, and synergistic potential of cell-free supernatant (CFSs) derived from Levilactobacillus brevis (Lb-CFS) and Lactiplantibacillus plantarum (Lp-CFS) against Klebsiella pneumoniae. Both CFSs exhibited potent growth inhibition, with minimum inhibitory concentrations (MICs) of 128μg/mL and 64μg/mL for Lb-CFS and Lp-CFS, respectively, and demonstrated dose-dependent bactericidal activity, achieving complete bacterial eradication at minimum bactericidal concentrations (MBC) within 6h. The CFSs suppressed the expression of virulence genes (galF, wzi, and manC) and biofilm formation in a dose-dependent manner. Synergistic interactions were observed when combining CFSs with antibiotics, resulting in 2- to fourfold reductions in antibiotic MICs and MBCs. Notably, adaptive evolution experiments revealed significantly slower resistance development in K. pneumoniae against CFSs (twofold MIC/MBC increase) compared to antibiotics (16- to 128-fold increase) after 21days. Furthermore, CFS-adapted strains exhibited increased antibiotic susceptibility, while antibiotic-adapted strains displayed cross-resistance to multiple antibiotics. No cross-resistance occurred between Lb-CFS and Lp-CFS, suggesting distinct adaptive mechanisms. These findings highlight the potential of probiotic-derived CFSs as effective antimicrobials with a lower propensity for inducing rapid resistance compared to conventional antibiotics, suggesting their promise in combating multidrug-resistant infections.

Impact of Helicobacter pylori Eradication on Inflammatory Bowel Disease Onset and Disease Activity: To Eradicate or Not to Eradicate?

Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies.

Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus

Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S. aureus infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-staphylococcal antibiotics are examined using both quantitative proteomics and transposon sequencing. These screens indicate that arginine metabolism is involved in antibiotic tolerance within a biofilm and support the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH, the final gene in the arginine synthesis pathway, induces antibiotic tolerance. Arginine restriction induces antibiotic tolerance via inhibition of protein synthesis. In murine skin and bone infection models, an argH mutant has enhanced ability to survive antibiotic treatment with vancomycin, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.

Characterization of biofilm-forming ability and antibiotic resistance profiles of clinical Pseudomonas aeruginosa isolates from patients with cystic fibrosis

Background: Pseudomonas aeruginosa is a key pathogen in cystic fibrosis (CF) associated infections, known for its biofilm-forming ability and resistance to multiple antibiotics. Understanding the relationship between biofilm production and antibiotic resistance profiles in clinical isolates can guide treatment strategies. Aims and Objectives: The aims of this study were to investigate the biofilm-forming abilities and antibiotic resistance profiles of clinical P. aeruginosa isolates from patients with CF and to determine the relationship between these two factors and their impact on treatment efficacy. Materials and Methods: A cross-sectional study was conducted on 100 clinical isolates of P. aeruginosa from CF patients. Biofilm-forming capacity was categorized as strong, moderate, or weak based on quantitative assays. Antibiotic resistance was assessed for ciprofloxacin, tobramycin, ceftazidime, meropenem, and piperacillin/tazobactam. Multi-drug resistance was defined as resistance to three or more antibiotic classes. Statistical correlations between biofilm-forming capacity and resistance levels were evaluated using the Chi-square tests. Results: Fifty-six percentages of isolates were strong biofilm producers, while 34% and 10% were moderate and weak producers, respectively. The highest antibiotic resistance was observed against ciprofloxacin (60%), followed by tobramycin (50%) and ceftazidime (45%). Forty percentages of the isolates were classified as multi-drug resistant. Strong biofilm producers demonstrated a significantly high correlation with antibiotic resistance (P&lt;0.05). Two predominant clonal groups were identified among the isolates, suggesting a possible clonal spread of resistance traits. Conclusion: The study confirms a strong association between robust biofilm production and heightened antibiotic resistance in P. aeruginosa isolates from CF patients. These findings highlight the need for targeted therapeutic strategies to disrupt biofilm formation and curb resistance spread.

Green synthesis of zinc oxide nanoparticles and its antibacterial Activity on Pseudomonas aeruginosa

Zinc oxide (ZnO) nanoparticles have wide-ranging applications and can be synthesized using environmentally friendly green synthesis methods as an alternative to conventional approaches. Pseudomonas aeruginosa (P. aeruginosa) is an extremely perilous bacterium known for its multidrug-resistant (MDR) nature, posing a significant threat to hospitalized patients and those with compromised immune systems. The bacterium's ability to withstand multiple antibiotics, combined with its capacity to form biofilms, contributes to its high rates of morbidity and mortality. The intrinsic resistance of P. aeruginosa, along with its ability to form biofilms, further complicates treatment and exacerbates the severity of infections, particularly in susceptible patient populations. Objective: The main objective of this study was to utilize extracts from Ocimum basilicum leaves in a green synthesis approach to produce zinc oxide nanoparticles. Additionally, the research aimed to assess the antibacterial effectiveness of these synthesized nanoparticles against P. aeruginosa. Materials and Methods: In this study, ZnO nanoparticles were synthesized using the leaf extract of O. basilicum plants under various parameters. The biosynthesis of zinc oxide nanoparticles was verified using a UV-visible spectrophotometer and characterized using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Fourier Transform Infrared Spectroscopy (FTIR). The synthesized ZnO nanoparticles exhibited significant antibacterial efficacy. Specifically, they demonstrated antimicrobial activity against P. aeruginosa pathogens. Different concentrations of both O. basilicum extract and synthesized ZnO nanoparticles were tested against P. aeruginosa and observed antibacterial activity. Results: indicated that the ZnO NPs synthesized from O. basilicum exhibited stronger antibacterial activity compared to the plant extract alone. The most effective concentrations were found to be 1.0, 1.5, and 3 mg/ml of prepared ZnO nanoparticles. Increasing the concentration of ZnO nanoparticles resulted in enhanced inhibition of bacterial growth in P. aeruginosa. Conclusion: The green synthesis of ZnO NPs using plant extracts has demonstrated significant antibacterial activity against P.aeruginosa. The high concentration of the ZnO NPs resulted in larger inhibition zones at higher concentrations. These findings underscore the possibility of green-synthesized ZnO NPs as an antimicrobial agent for P. aeruginosa. The environmentally friendly and cost-effective nature of the green synthesis method further enhances its appeal for future applications in antibacterial treatments.

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Molecular typing of reduced susceptibility of Acinetobacter calcoaceticus-baumannii complex to Chlorhexidine in Turkey by pulsed-field gel electrophoresis.

Introduction. The global spread of Acinetobacter spp., particularly the Acinetobacter calcoaceticusbaumannii (ACB) complex, has led to its recognition as a significant pathogen by the World Health Organization (WHO). The increasing resistance of the ACB complex to multiple antibiotics presents a challenge for treatment, necessitating accurate antibiotic susceptibility profiling after isolation.Hypothesis or gap statement. There is limited understanding of the antimicrobial resistance and chlorhexidine, a biocide, susceptibility profiles of ACB complex strains, especially in clinical settings in Turkey.Aim. This study aimed to identify ACB complex strains recovered from various clinical specimens at Hacettepe University Hospitals in Ankara, Turkey, in 2019, and to assess identification, their antibiotic and chlorhexidine susceptibility profiles, and genomic relatedness.Methodology. Eighty-two ACB complex strains were identified using MALDI-TOF MS. Susceptibility testing to 12 antibiotics was conducted using the disc diffusion method, and colistin, chlorhexidine susceptibility was assessed using the broth microdilution technique, following the latest EUCAST and CLSI guidelines. ACB complex members with reduced chlorhexidine sensitivity were further analyzed by pulsed-field gel electrophoresis (PFGE) for bacterial typing.Results. Among the isolates, 1.2% were multidrug-resistant (MDR), 73.2% were extensively drug-resistant (XDR), and 12.2% were pandrug-resistant (PDR). Carbapenem resistance was found in 86.7% of MDR, PDR, and XDR strains. Colistin resistance was observed in 15.8% of isolates, and 18.2% exhibited decreased susceptibility to chlorhexidine. PFGE revealed seven different clones among strains with reduced chlorhexidine sensitivity, indicating vertical transmission within the hospital.Conclusion. This study highlights the reduced susceptibility to chlorhexidine in ACB complex members and provides epidemiological insights into their spread. The findings underscore the importance of screening for antimicrobial resistance and biocide susceptibility profiles to effectively manage healthcare-associated infections.

The synergy effect of matrine and berberine hydrochloride on treating colibacillosis caused by an avian highly pathogenic multidrug-resistant Escherichia coli

Infection by multidrug-resistant avian pathogenic Escherichia coli (APEC) in chickens always leads to the uselessness of antibiotics, highlighting the need for alternative antibacterial agents. Sophora flavescens and Coptis chinensis have been a classical combination used together in Traditional Chinese Medicine (TCM) formulas to treat diseases with similar symptoms to colibacillosis for an extended period, but the effect of their active ingredients' combination on APEC infection remains unstudied. The objective of this study was to explore the synergistic effect of matrine and berberine hydrochloride on colibacillosis caused by an isolated multidrug-resistant APEC. In this study, a highly pathogenic E. coli was isolated from the liver of a diseased chicken in a farm suspected of colibacillosis, and it was resistant to multiple antibiotics. The LD50 of the strain was approximately 3.759×108 CFU/mL. The strain harbored several antibiotic resistance genes and virulence genes. Matrine and berberine hydrochloride have synergistic antibacterial effect against the isolated strain in vitro. The combined use of matrine and berberine hydrochloride exhibited synergistic effects in the treatment of APEC infection by regulating the organ indices, improving the pathological situation, decreasing the bacterial load, and regulating the inflammatory factors to enhance the survival rate of chickens in vivo. These results provided a foundation for revealing the effective effects and possible mechanisms of matrine and berberine hydrochloride as potential antimicrobial agents on diseases caused by multidrug-resistant APEC in chickens.

The overview of Clarithromycin treatment for Helicobacter pylori infection

Helicobacter pylori (H. pylori) is a Gram-negative bacillus that causes infections worldwide. Helicobacter pylori's drug resistance and infectivity are vital factors causing Helicobacter pylori infection. The virulence factors of Helicobacter pylori include acid escape virulence factors and epithelial cell colonizing factors, which can directly or indirectly cause chronic gastritis or gastric ulcer. As the resistance of Helicobacter pylori increases, a combination of multiple antibiotics is now the recommended therapy, and clarithromycin is one of them. The production process of clarithromycin and its effectiveness are essential points of discussion.

Comparing amoxicillin and trimethoprim: Overall performance in combating Escherichia coli-causing urinary tract infection

Urinary Tract Infection (UTI) is one of the most prevalent bacterial infections in the world, and 80% of reported UTI cases are derived by gram negative bacteria Escherichia coli. Uropathogenic Escherichia coli is strongly adaptive and resilient against immune response, forming Intracellular Bacterial Communities (IBC) inside uroepithelium cells that constitute the urethra and the bladder. Their rapid absorption of cellular nutrients enables them to advance upward toward the kidney and cause inflammation. Hence, based on the perceived severity of UTI, multiple antibiotics are used to treat UPEC-causing UTI. This article provides a detailed review on the contemporary performance of amoxicillin and trimethoprim, both widely used to treat UPEC-causing UTI for decades. Amoxicillin is a penicillin-derivative that produces bactericidal by inhibiting transpeptidase to disrupt peptidoglycan synthesis, causing rapid-growing bacteria to lyse. It is a well-tolerated drug that can be used on pregnant patients. Resistant UPEC develop beta-lactamase to counter amoxicillin. Trimethoprim, on the other hand, is a dihydropyrimidine antibiotic that impedes the production of tetrahydrofolic acids, producing either bacteriostatic or bactericidal effects. Resistant UPEC transforms the shape of tetrahydrofolic acids-producing enzyme, dihydrofolic reductase, to resist trimethoprim. Although amoxicillin and trimethoprim are competitive inhibitors are effective against a variety of gram-positive and gram-negative species, trimethoprim, in statistical study, is proven to be more effective than amoxicillin in treating gram-negative UTI. Today, the wide-spread resistant strains of UPEC exists for both drugs. Thus, amoxicillin and trimethoprim are implemented mainly through combination therapies, amoxicillin/clavulanate and trimethoprim sulfamethoxazole, respectively. These combinations are more effective than the drugs to be used alone and are able to counter some resistant strains, but UPEC that are resistant to combinations also exists. Regardless, both amoxicillin and trimethoprim are still used as first-line antibiotics, while more powerful antibiotics are reserved for special multi-resistant superbugs.