Emergence Of Antibiotic Resistance Research Articles

Effectiveness of Ceftazidime/Avibactam treatment for infections caused by Klebsiella pneumoniae Carbapenemase (KPC), a 30-day mortality perspective. Comparison of results with control groups treated with other antibiotics

Introduction: Infections caused by Klebsiella pneumoniae carbapenemase (KPC) pose a significant clinical challenge due to increasing antibiotic resistance. This study analyzes the effectiveness of ceftazidime/avibactam treatment for KPC infections, focusing on 30-day mortality and comparing results with control groups treated with different antibiotics. Material and methods: We conducted a retrospective analysis of six cohort studies, comparing thirty-day mortality in patients treated with ceftazidime/avibactam with control groups using other antibiotics. The studies included patients infected with KPC, and the analysis focused on therapeutic effectiveness. Aim of the study: The aim of the study is to compare the results in terms of 30-day mortality in groups treated with ceftazidime/avibactam compared to control groups using different antibiotics. Conclusions: Data analysis from various studies revealed varied 30-day mortality outcomes in groups treated with ceftazidime/avibactam compared to control groups using different antibiotics. Ceftazidime/avibactam proved to be more effective in all studies, reducing mortality rates compared to other treatment regimens. We emphasize that emerging antibiotic resistance, especially in the case of KPC, requires a comprehensive therapeutic approach. Despite promising ceftazidime/avibactam results, factors such as overall patient health and treatment delays may influence final therapy outcomes. We also highlight controversies regarding combination therapy vs. monotherapy, necessitating further research. Our work underscores the importance of monitoring the effectiveness of KPC infection treatment and exploring new therapeutic strategies. Further clinical studies are essential to develop a fuller understanding and optimal therapeutic protocols in the face of the growing antibiotic resistance problem.

Effect of Mineral Fertilizers and Pesticides Application on Bacterial Community and Antibiotic-Resistance Genes Distribution in Agricultural Soils

Soils are a hotspot for the emergence and spread of antibiotic resistance. The effects of agrochemical treatments on the bacterial community of agricultural soils and the content of antibiotic-resistance genes (ARGs) were studied. Treatments included the following: control, mineral fertilizers (NPKs), pesticides, and the combined treatment of soils under soya (Glycine max), sunflower (Helianthus annuus L.), and wheat (Triticum aestivum). Bacterial community taxonomic composition was studied using 16S rRNA gene sequencing. The content of 10 ARGs and 3 integron genes (intI1, intI2, intI3) was determined using quantitative real-time PCR. The results showed that the treatments had little effect on the taxonomic composition and diversity of the soil bacterial community. The most significant factors determining differences in the microbial community were sampling time and soil physico-chemical parameters. A significant role of the bacterial community in ARG distribution in soils was demonstrated. Representatives of the Pseudomonas, Bacillus, Sphingomonas, Arthrobacter genera, and the Nocardioidaceae and Micrococcaceae families were likely ARG hosts. The presence of integron genes of all three classes was detected, the most numerous being intI3. This work provides important information on the role of agricultural soils in ARG transfer, and the findings may be useful for sustainable and safe agricultural development.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1β levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

Biocontrol characteristics and application of phage SEP4 against multidrug-resistant Salmonella biofilm on food matrix

The emergence of antibiotic resistance and biofilm formation among Salmonella strains, especially in chicken meat, poses substantial risks to economic and public health. To mitigate these challenges, we explored interventions and biofilm inhibition strategies against multidrug-resistant serovars (B, C1, and D groups), by Salmonella phage SEP4, an isolate with broad host-spectrum. The morphological and genomic analyses classified it as a member of the Siphoviridae family with an icosahedral head of 124.56 ± 8.9 nm diameter and 66.28 ± 2.01 nm tail length, respectively. Phage SEP4 displayed robust survivability over a pH range of 3–10 and temperatures from 30 °C to 60 °C. Phage adsorption peaked at 73.20% in 15 min, with a burst size of 119 PFU/CFU at optimal MOI-1. Moreover, a linear double-stranded DNA genome of 41,828 bp, characterized by 49.84% GC content and putative 57 open reading frames (ORFs), and lacked antibiotic or virulence factor genes. Anti-Salmonella phage efficacy demonstrated a significant reduction in viable cell counts at 25 °C compared to 4 °C against tested MDR strains in food models. The bactericidal activity of phage SEP4 ranged from 14% to 46% and 25%–33.8% against host at MOI-1 and 100, while 22%–37% for other MDR strains. Simultaneously, SEP4 inhibited the growth of matured biofilms on lettuce leaves and chicken surfaces, achieving complete reduction within 4–6 h. SEM images confirmed the drastic destruction of cohesive biofilm architectures by phage treatment. The findings show that phage SEP4 has promising potential as a biocontrol agent, ensuring food safety by controlling MDR Salmonella contaminations and associated biofilms.

The spectrum of pneumonia among intubated neonates in the neonatal intensive care unit.

We review the pathophysiology, epidemiology, diagnosis, treatment, and prevention of ventilator-associated pneumonia (VAP) in neonates. VAP has been studied primarily in adult ICU patients, although there has been more focus on pediatric and neonatal VAP (neo-VAP) in the last decade. The definition as well as diagnosis of VAP in neonates remains a challenge to date. The neonatal intensivist needs to be familiar with the current diagnostic tools and prevention strategies available to treat and reduce VAP to reduce neonatal morbidity and the emergence of antibiotic resistance. This review also highlights preventive strategies and old and emerging treatments available.

Microbiological Quality and Antimicrobial Resistance Profile of Bacterial Isolates from Locally and Industrially Processed Noni (Morinda citrifolia) Drinks Sold in Port Harcourt, Nigeria

Public health is seriously threatened by the emergence of antibiotic resistance, especially in food products. The purpose of this study was to evaluate the Microbiological Quality and Antimicrobial Resistance Profile of Bacterial Isolates from locally and Industrially Processed NONI (Morinda citrifolia) Drinks Sold in Port Harcourt, Nigeria. Noni beverages (samples) were bought from three distinct locations in Rivers State while the fruits were locally fermented into noni beverages. Conventional microbiological methods were employed to identify the bacterial isolates, and the disc diffusion method was employed to assess the antibiotics susceptibility. Characterization of the bacterial isolates was further done using molecular techniques. The total heterotrophic bacteria in the beverages ranged from 3.5±0.7 to 5.9±0.3×104 cfu/ml. The total coliform counts ranged from 1.7±1.9 to 3.8±1.2×104 CFU/ml and faecal coliform count in all the samples was zero (0). Data showed that the locally produced noni sample had the highest bacterial counts (1.6×103 cfu/ml) while the lowest count was observed in samples from location B (1.50×102 cfu/ml). The presence of multiple bacterial species, including Flavobacterium spp. (16.7%), Enterobacter spp. (25%), Serratia spp. (25%), Micrococcus spp. (8.3%) and Bacillus spp. (25%) was indicated by the results. All the isolates (100%) were resistant to commonly used antibiotics such as cefuroxime, cefotaxime, cefixime and meropenem, gentamycin, vancomycin, with 66.7% being resistant to ampiclox. Ampicillin resistance gene (Amp C gene) was detected in Serratia marcescens AB061685.1 and Bacillus subtilis AB192294.2. These findings have shown that Noni beverages are prone to bacterial contamination with serious public health concerns and thus highlighted the significance of strict quality control measures in the production and sale of Noni drinks, to check the risk of antimicrobial resistance transmission through food consumption.

Intraspecific variation in antibiotic resistance potential within E. coli.

Intraspecific genomic diversity brings the potential for an unreported and diverse reservoir of cryptic antibiotic resistance genes in pathogens, as cryptic resistance can occur without major mutations and horizontal transmission. Here, we predicted the differences in the types of antibiotics and genes that induce cryptic and latent resistance between micro-diverse Escherichia coli strains. For example, we hypothesize that known resistance genes will be the culprit of latent resistance within clinical strains. We used a modified functional metagenomics method to induce expression in eight E. coli strains. We found a total of 66 individual genes conferring phenotypic resistance to 11 out of 16 antibiotics. A total of 14 known antibiotic resistance genes comprised 21% of total identified genes, whereas the majority (52 genes) were unclassified cryptic resistance genes. Between the eight strains, 1.2% of core orthologous genes were positive (conferred resistance in at least one strain). Sixty-four percent of positive orthologous genes conferred resistance to only one strain, demonstrating high intraspecific variability of latent resistance genes. Cryptic resistance genes comprised most resistance genes among laboratory and clinical strains as well as natural, semisynthetic, and synthetic antibiotics. Known antibiotic resistance genes primarily conferred resistance to multiple antibiotics from varying origins and within multiple strains. Hence, it is uncommon for E. coli to develop cross-cryptic resistance to antibiotics from multiple origins or within multiple strains. We have uncovered prospective and previously unknown resistance genes as well as antibiotics that have the potential to trigger latent antibiotic resistance in E. coli strains from varying origins.IMPORTANCEIntraspecific genomic diversity may be a driving force in the emergence of adaptive antibiotic resistance. Adaptive antibiotic resistance enables sensitive bacterial cells to acquire temporary antibiotic resistance, creating an optimal window for the development of permanent mutational resistance. In this study, we investigate cryptic resistance, an adaptive resistance mechanism, and unveil novel (cryptic) antibiotic resistance genes that confer resistance when amplified within eight E. coli strains derived from clinical and laboratory origins. We identify the potential of cryptic resistance genes to confer cross-resistance to antibiotics from varying origins and within multiple strains. We discern antibiotic characteristics that promote latent resistance in multiple strains, considering intraspecific diversity. This study may help detect novel resistance genes and functional genes that could become responsible for cryptic resistance among diverse strains and antibiotics, thus also identifying potential novel antibiotic targets and mechanisms.

Prevalence of self-medication practices in the Maharashtra population: a cross-sectional study

Background: Self-medication is a significant issue in public health, with varying global prevalence. It is one of the major causes of the emergence of antibiotic resistance in India. The study's objective was to identify the pattern, cause, and adverse events of self-medication in Maharashtra's urban and rural areas. Methods: A cross-sectional survey was conducted using a pre-populated questionnaire; including information on age (18-85 years), non-prescription and prescription medication use. Age, gender, past medical and medication history, social history, and self-medication pattern, frequency, reason, source of information, and adverse events noticed as a result of self-medication are all sociodemographic questions on the questionnaire. A percentage analysis was used to examine the data. Results: Study states that out of 400 sample, 76% of the individuals self-medicate, with painkillers (49.4%), antacids (23.7%), antibiotics (15.3%), being the most often used drugs for ailments like headache, fever, bodily pain, and acidity. The top most medications taken for self-medication are paracetamol (53.1%), pantoprazole (30.43%), ondansetron (13.62%), and azithromycin (12.46%); 66.07% usage of prescription drugs as self-medication was found. The most frequent causes of self-medication were discovered to be mild illnesses, the easy accessibility of medications, and chemist recommendations, 8% of those surveyed had adverse events, and sources of information were chemists, past prescriptions, family members, and acquaintances. Conclusions: In Maharashtra, self-medication is a prevalent practice that primarily utilizes over-the-counter (OTC) drugs. As a result, consumers should be made aware of the hazards of antibiotic resistance and other pharmaceuticals.

ANTIBIOTICS RESISTANCE PREDICTION USING MACHINE LEARNING ALGORITHMS

Opioid Risk Antibiotics Resistance abuse, overdose, and drug addiction have become public health concerns as a result of the notable increase in the use of both prescribed and over-the-counter medications in the United States. The growing incidence of opioid usage presents a complex public health issue, one of which is the possible influence on antibiotic resistance. The existing system predicts antibiotic resistance profiles in bacterial infections among hospitalized patients using machine learning (ML) algorithms and electronic medical records (EMRs). However, it ignores the impact of opioid use, a major public health issue that may be connected to antibiotic resistance. The complex association between opioid-related behaviors and antibiotic resistance may not be adequately captured by powerful machine learning algorithms, despite their use. The larger context of antibiotic resistance patterns is limited by the lack of linkage with data on opioid intake. The proposed abstract aims to improve predictive accuracy and understanding of the complex factors influencing antibiotic resistance emergence by integrating support vector machines (SVM) and linear regression to thoroughly analyse the relationship between opioid risk and antibiotic resistance. This approach addresses these limitations. We suggested combining linear regression and support vector machines (SVM) to better understand the complex connection between opioid risk and antibiotic resistance. In order to pinpoint the main causes of increased risk, trends in opioid consumption data are analyzed using the SVM model. In parallel, the relationship between opioid abuse and the rise in antibiotic resistance is examined using linear regression. Our goal is to have a thorough grasp of the complex relationship between opioid-related behaviors and the emergence of antibiotic resistance by combining these two analytical approaches. This project is designed under NetBeans with java as front end. Weka tool for machine learning analysis Keywords: Antibiotic Resistance, Machine Learning, Bacterial Infections, Global Crisis, Healthcare.

Effects of feeding pasteurized waste milk or saleable milk to calves on weight, health and fecal Escherichia coli antimicrobial resistance.

The aim of this study was to compare the effects of feeding pasteurized waste milk or saleable milk to calves on weight, health and emergence of antimicrobial resistance in Escherichia coli strains isolated from those calves. An experimental study under field conditions on a commercial pasture-based Argentinian dairy farm was carried out. Forty Holstein calves were assigned randomly to either pasteurized waste milk (PWM) or non-pasteurized saleable milk (SM). The antimicrobial agents (AM) used on the farm, both to treat or prevent diseases, were recorded. The passive immunity level, calf live weight, AM presence in milk, clinical examination of calves, and E. coli isolation and identification, were performed. A total of 258 E. coli strains were isolated from fecal samples (132 isolates from SM calves and 126 from PWM calves at six sampling times). All E. coli isolated were used to perform AM susceptibility tests (disc diffusion and agar dilution). No differences were observed between groups in health parameters, average daily gain or prevalence of resistant E. coli strains to any AM evaluated throughout the study. Peaks of trimethoprim, sulfamethoxazole and enrofloxacin minimum inhibitory concentration (MIC) were observed at 30 d in E. coli from both groups of calves, whilst additional peaks to tetracyclin and ampicillin were observed only in SM calves. All MIC apart from gentamicin decreased at 75 and 90 d of age (during the weaning period). Gentamicin MIC behaved differently, having no peaks and increasing at 90 d only in PWM group. In conclusion, we found no evidence that emergence of antibiotic resistance is related to the consumption of pasteurized waste milk.

Trends of Antimicrobial Susceptibility of Neisseria gonorrhoeae isolates between 2012 and 2023: results from an open Italian cohort.

Neisseria gonorrhoeae (Ng) is a public health priority due to the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration (MIC) and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), ciprofloxacin (CIP) over a 10-year period. Retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral and pharyngeal samples at San Raffaele Scientific Institute, between September 2012-February 2023. MICs of antibiotics were determined by gradient-test strips. Bivariate linear regression models, applied on logarithmic MICs values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains. 436 Ng isolates from 352 individuals were analyzed. MICs of CRO and PenG reduced over time (p < 0.001, p = 0.030), AZM increased (p = 0.001), CIP and TET did not change (p = 0.473, p = 0.272). The percentages of resistant strains were: PenG 89.9%, TET 90.8%, CIP 48.2%, AZM 4.4%; CRO-DS strains were 8.7%, only one CRO-R. The proportion of resistant strains increased over time for AZM (p = 0.007), TET (p = 0.001), CIP (p < 0.001), whereas decreased for PenG (p < 0.001) and CRO-DS/R strains (p < 0.001). Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment confirmed to be effective.

In vitro anti-Helicobacter pylori activity and antivirulence activity of cetylpyridinium chloride.

The primary treatment method for eradicating Helicobacter pylori (H. pylori) infection involves the use of antibiotic-based therapies. Due to the growing antibiotic resistance of H. pylori, there has been a surge of interest in exploring alternative therapies. Cetylpyridinium chloride (CPC) is a water-soluble and nonvolatile quaternary ammonium compound with exceptional broad-spectrum antibacterial properties. To date, there is no documented or described specific antibacterial action of CPC against H. pylori. Therefore, this study aimed to explore the in vitro activity of CPC against H. pylori and its potential antibacterial mechanism. CPC exhibited significant in vitro activity against H. pylori, with MICs ranging from 0.16 to 0.62 μg/mL and MBCs ranging from 0.31 to 1.24 μg/mL. CPC could result in morphological and physiological modifications in H. pylori, leading to the suppression of virulence and adherence genes expression, including flaA, flaB, babB, alpA, alpB, ureE, and ureF, and inhibition of urease activity. CPC has demonstrated in vitro activity against H. pylori by inhibiting its growth, inducing damage to the bacterial structure, reducing virulence and adherence factors expression, and inhibiting urease activity.

Evolution of Urinary Tract Infection Understanding: From Ancient Insights to Contemporary Perspectives

This research delves into the historical understanding and evolutionary trajectory of urinary tract infections (UTIs) from ancient descriptions to modern comprehension. The study explores the historical perspectives from ancient Egyptian insights to Hippocratic beliefs and traces the evolution of management approaches until the discovery of microorganisms as causative agents. Advancements in antimicrobial therapy and the changing landscape of UTI treatment strategies are also outlined, considering the emergence of antibiotic resistance. Defining UTI, the research emphasizes the differentiation between asymptomatic bacteriuria and UTI, highlighting crucial aspects and clinical implications. The prevalence of UTIs across different demographics and regions, especially in children, is examined. Variations in prevalence rates and contributing factors are explored in detail, considering regional disparities, age groups, and gender differences. Moreover, the research identifies several risk factors contributing to UTI occurrence, including gender, age, uncircumcision in males, improper toilet training, vesicoureteral reflux, and other anatomical and behavioral aspects. It also delves into the pathophysiology of UTIs, elucidating the multifaceted factors involved, such as aetiologic agents, anatomical variations, immunological factors, and genetic influences affecting the location, course, and prognosis of UTIs. The clinical forms of UTIs, namely acute pyelonephritis and cystitis, are outlined, delineating the symptoms, diagnostic approaches, and clinical implications associated with each form. The research emphasizes the importance of accurate differentiation between these clinical forms for appropriate treatment and long-term consequences, particularly renal scarring and other complications associated with pyelonephritis. In summary, this comprehensive review consolidates historical insights, epidemiological trends, risk factors, pathophysiological mechanisms, and clinical manifestations to offer a holistic understanding of UTIs, providing valuable insights for effective management and future research directions. Keywords: Urinary tract infection, historical perspective, prevalence, risk factors, pathophysiology, clinical forms, antimicrobial therapy.

A nucleoid-associated protein is involved in the emergence of antibiotic resistance by promoting the frequent exchange of the replicative DNA polymerase in Mycobacterium smegmatis.

Unlike many other pathogens, Mycobacterium tuberculosis has limited ability for horizontal gene transfer, a major mechanism for developing antibiotic resistance. Thus, the mechanisms that facilitate chromosomal mutagenesis are of particular importance in mycobacteria. Here, we show that Lsr2, a nucleoid-associated protein, has a novel role in DNA replication and mutagenesis in the model mycobacterium Mycobacterium smegmatis. We find that Lsr2 promotes the fast exchange rate of the replicative DNA polymerase, DnaE1, at the replication fork and is important for the effective loading of the DnaE2-ImuA'-ImuB translesion complex. Without lsr2, M. smegmatis replicates its chromosome more faithfully and acquires resistance to rifampin at a lower rate, but at the cost of impaired survival to DNA damaging agents. Together, our work establishes Lsr2 as a potential factor in the emergence of mycobacterial antibiotic resistance.

Phage-antibiotic combinations in various treatment modalities to manage MRSA infections.

Introduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are multi-drug resistant in nature. Methods: In this study, we examined the combined impact of the staph phage vB_Sau_S90 and four antibiotics on methicillin-resistant Staphylococcus aureus (MRSA). We conducted experiments on three different treatment sequences: a) administering phages before antibiotics, b) administering phages and antibiotics simultaneously, and c) administering antibiotics before phages. Results: When the media was supplemented with sub-inhibitory concentrations of 0.25μg/mL and 1μg/mL, the size of the plaque increased from 0.5 ± 0.1mm (in the control group with only the phage) to 4 ± 0.2mm, 1.6 ± 0.1mm, and 1.6 ± 0.4mm when fosfomycin, ciprofloxacin, and oxacillin were added, respectively. The checkerboard analysis revealed a synergistic effect between the phages and antibiotics investigated, as indicated by a FIC value of less than 0.5. The combination treatment of phages and antibiotics demonstrated universal efficacy across all treatments. Nevertheless, the optimal effectiveness was demonstrated when the antibiotics were delivered subsequent to the phages. Utilizing the Galleria mellonella model, in vivo experiments showed that the combination of phage-oxacillin effectively eliminated biofilm-infected larvae, resulting in a survival rate of up to 80% in the treated groups. Discussion: Our findings highlight the advantages of using a combination of phage and antibiotic over using phages alone in the treatment of MRSA infections.

The Results of Work of Infectious Disease Specialists and Epidemiologists of the Rospotrebnadzor during the Outbreak of Acute Intestinal Infections in the Republic of the Congo (Brazzaville) in 2023

This paper provides an analysis of the results of joint work of Russian and Congolese infectious disease specialists and epidemiologists to decipher the etiology and causes of the outbreak of intestinal infections in Dolisie (Republic of the Congo) in the summer of 2023. It has been found that the increase in the incidence of intestinal infections was caused mainly by the agents of typhoid fever and dysentery; tropical malaria was a combined pathology. No cases of cholera patient detection were registered. Failure of water supply system, domestic disrepair, and low public awareness about prevention of intestinal infections contributed to the active transmission of pathogens. The combination of epidemic process manifestations testified to the aquatic nature of the outbreak. Also, cases of pathogen transmission through contact household route were recorded, food transmission was not excluded. Patients with severe and complicated forms of typhoid fever and shigellosis accounted for 50 % of those hospitalized. There was delay in seeking medical care. The available regimens of antibacterial therapy were ineffective, since there was no possibility of laboratory confirmation of the diagnosis with determination of sensitivity to drugs. Uncontrolled treatment facilitated the emergence of antibiotic resistance in pathogens, prolonged bacterial release and subsequent spread of infection. Infectious disease specialists and epidemiologists of the Rospotrebnadzor provided consulting and practical assistance to Congolese colleagues, developed and presented recommendations for optimizing anti-epidemic and therapeutic measures, taking into account the results of assessment of the causes for onset and development of the outbreak.

''Myth Busting in Infectious Diseases'': A Comprehensive Review.

Antibiotics have played a pivotal role in modern medicine, drastically reducing mortality rates associated with bacterial infections. Despite their significant contributions, the emergence of antibiotic resistance has become a formidable challenge, necessitating a re-evaluation of antibiotic use practices. The widespread belief in clinical practice that bactericidal antibiotics are inherently superior to bacteriostatic ones lacks consistent support from evidence in randomized controlled trials (RCTs). With the latest evidence, certain infections have demonstrated equal or even superior efficacy with bacteriostatic agents. Furthermore, within clinical practice, there is a tendency to indiscriminately order urine cultures for febrile patients, even in cases where alternative etiologies might be present. Consequently, upon obtaining a positive urine culture result, patients often receive antimicrobial prescriptions despite the absence of clinical indications warranting such treatment.Furthermore, it is a prevailing notion among physicians that extended durations of antibiotic therapy confer potential benefits and mitigate the emergence of antimicrobial resistance. Contrary to this belief, empirical evidence refutes such assertions. This article aims to address common myths and misconceptions within the field of infectious diseases.

Investigating Biofilms: Advanced Methods for Comprehending Microbial Behavior and Antibiotic Resistance.

Biofilms, which consist of microorganisms enclosed in an extracellular polymeric material (EPS), hold immense importance in the fields of environmental research, industry, and medicine. They play a significant role in ecosystem dynamics and stability, but they also pose issues such as biofouling, corrosion, and pollution. Biofilms in medical environments are linked to persistent infections and elevated healthcare expenses. The EPS matrix plays a crucial role in maintaining the structural integrity and antibiotic resistance of these structures. The research primarily investigates the role of the EPS matrix in facilitating horizontal gene transfer among biofilm communities, with a particular emphasis on EPS and its impact on this process. The process is recognized as a pivotal mechanism in the emergence of antibiotic resistance, underscoring the crucial function of EPS in the dynamics of biofilms. The analysis also highlights the significant financial constraints caused by biofilms in several industries. Biofilm-associated infections in the healthcare sector result in escalated treatment expenses and extended hospitalization periods. In an industrial context, biofilms have a role in increasing maintenance expenses and product contamination, emphasizing the need for efficient management solutions. This review presents the most recent progress in biofilm research, emphasizing the utilization of sophisticated imaging tools and molecular methodologies. In addition to conventional imaging techniques, the research explores the utilization of sophisticated molecular tools, such as DNA and RNA sequencing, in conjunction with proteomics. These approaches are essential for assessing the genetic and metabolic mechanisms that regulate biofilm development and antibiotic resistance. The review underscores the significance of employing an interdisciplinary methodology in the study of biofilms. By incorporating a range of approaches, such as sophisticated imaging and molecular analysis, a comprehensive understanding of biofilm dynamics may be achieved. This approach also opens up possibilities for developing novel solutions to address the negative impacts of biofilms on health, industry, and the environment.

Real-time monitoring of replication errors’ fate reveals the origin and dynamics of spontaneous mutations

The efficiency of replication error repair is a critical factor governing the emergence of mutations. However, it has so far been impossible to study this efficiency at the level of individual cells and to investigate if it varies within isogenic cell populations. In addition, why some errors escape repair remains unknown. Here we apply a combination of fluorescent labelling of the Escherichia coli Mismatch Repair (MMR) complex, microfluidics, and time-lapse microscopy, to monitor in real-time the fate of >20000 replication errors. We show that i) many mutations result from errors that are detected by MMR but inefficiently repaired ii) this limited repair efficiency is due to a temporal constraint imposed by the transient nature of the DNA strand discrimination signal, a constraint that is likely conserved across organisms, and iii) repair capacity varies from cell to cell, resulting in a subpopulation of cells with higher mutation rate. Such variations could influence the fitness and adaptability of populations, accelerating for instance the emergence of antibiotic resistance.

Rational molecular design converting fascaplysin derivatives to potent broad-spectrum inhibitors against bacterial pathogens via targeting FtsZ

The filamentous temperature-sensitive mutant Z protein (FtsZ), a key player in bacterial cell division machinery, emerges as an attractive target to tackle the plight posed by the ever growing antibiotic resistance over the world. Therefore in this regard, agents with scaffold diversities and broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens are highly needed. In this study, a new class of marine-derived fascaplysin derivatives has been designed and synthesized by Suzuki-Miyaura cross-coupling. Some compounds exhibited potent bactericidal activities against a panel of Gram-positive (MIC = 0.024–6.25 μg/mL) and Gram-negative (MIC = 1.56–12.5 μg/mL) bacteria including methicillin-resistant S. aureus (MRSA). They exerted their effects by dual action mechanism via disrupting the integrity of the bacterial cell membrane and targeting FtsZ protein. These compounds stimulated polymerization of FtsZ monomers and bundling of the polymers, and stabilized the resulting polymer network, thus leading to the dysfunction of FtsZ in cell division. In addition, these agents showed negligible hemolytic activity and low cytotoxicity to mammalian cells. The studies on docking and molecular dynamics simulations suggest that these inhibitors bind to the hydrophilic inter-domain cleft of FtsZ protein and the insights obtained in this study would facilitate the development of potential drugs with broad-spectrum bioactivities.