Era Of Antibiotic Resistance Research Articles

Effects of Lactobacillus spp. on Helicobacter pylori: A Promising Frontier in the Era of Antibiotic Resistance.

Helicobacter pylori, a pathogenic bacterium responsible for multiple gastrointestinal disorders, has emerged as a major global concern due to rise in antibiotic resistance. Unwanted side effects of antibiotics therapy are further complicating the treatment strategies. Consequently, an alternative approach, using probiotics has emerged as a promising solution for treating H. pylori infections. Probiotics have shown considerable potential in increasing the cure rate and reducing the side effects through diverse mechanisms. Among the widely employed probiotics, Lactobacillus spp. has garnered particular attention in this review. After reviewing the studies on effects of Lactobacillus spp. on H. pylori, it is evident that several Lactobacillus spp. have demonstrated their potential efficacy against H. pylori infection, when administered alone or in conjunction with antibiotics, in a strain-specific manner. Furthermore, the inclusion of Lactobacillus spp. in the treatment regimen has also been associated with a reduction in the side effects related to antibiotic-based therapies. Future research may focus on identifying optimal strains and treatment regimens, understanding the long-term impacts of use, and determining their role in preventing H. pylori infection in various populations.

A review of the fighting Acinetobacter baumannii on three fronts: antibiotics, phages, and nanoparticles.

In the current era of antibiotic resistance, researchers are exploring alternative ways to treat bacterial infections that are resistant to multiple drugs. Acinetobacter baumannii (A. baumannii) is a bacterium that is commonly encountered in clinical settings and is known to be resistant to several drugs. Due to the increase in drug-resistant infections caused by this bacteria, there is an urgent need to investigate alternative treatment options such as phage therapy and combination therapy. Despite the success of phages in some cases, there are some limitations in their clinical application that can be overcome by combining phages with other substrates such as nanoparticles to improve their function. The integration of nanotechnology with phage therapy against A. baumannii promises to overcome antibiotic resistance. By exploiting the targeted delivery and controlled release capabilities of nanoparticles, we can enhance the therapeutic potential of phages while minimizing their limitations. Continued research in this field will undoubtedly pave the way for more effective and precise treatments against A. baumannii infections and provide hope in the fight against antibiotic-resistant bacteria.

Efficient antiseptic prophylaxis in the era of antibiotic resistance

An excessive use of antibiotic preparations in daily practice frequently without clear medical indications has led to the development of dangerous strains of bacteria resistant to the available pharmaceutical drug. Today, antibiotics are used not only to treat infections, but also as preoperative infection prevention. Intravitreal injection is one of the most commonly performed ophthalmological procedures where, until recently, perioperative antibiotics prevention was recommended. Currently, antibiotics in this procedure are not advised at all. Nowadays, for anti-infective prophylaxis we use iodopovidone and preparations that combine antiseptic and soothing effects.

Resolution of Chronic Bacterial Prostatitis with Bacteriophage-antibiotic Therapy

Chronic bacterial prostatitis is a commonly diagnosed genitourinary infection that presents significant challenges both in diagnosis and treatment. In an upcoming era of antibiotic resistance, and limited therapeutic options it becomes imperative to revise current guidelines and to provide more effective treatment strategies. At the Eliava Phage Therapy Center (Tbilisi, Georgia) we utilize bacteriophage therapy as an alternative approach against chronic bacterial infections. Bacteriophages, viruses that target and lyse specific bacterial cells, can be used as a stand-alone treatment or in conjunction with antibiotics. We present a case report of a patient with prostatitis caused by Escherichia coli infection, who prior to addressing our clinic, has been receiving antibiotic therapy without any positive effect. Our approach of combined use of antibiotics and phages was successful not only in complete clinical improvement but also in total bacterial eradication. This outcome shows the potential of bacteriophage therapy as a valuable adjunct to conventional antibacterials in the management of prostatitis.

Synergistic removal of Staphylococcus aureus biofilms by using a combination of phage Kayvirus rodi with the exopolysaccharide depolymerase Dpo7.

Bacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance. This study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage (Rockefellervirus IPLA7) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis. Our results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.

In vitro antibacterial, antibiofilm activities, and phytochemical properties of Posidonia oceanica (L.) Delile: An endemic Mediterranean seagrass

In the antibiotic resistance era, utilizing understudied sources for novel antimicrobials or antivirulence agents can provide new advances against antimicrobial resistant pathogens. In this study, we aimed to investigate antibacterial and antibiofilm activities of Posidonia oceanica (L.) Delile against Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 and several S. aureus clinical isolates obtained from medical devices, including patient urinary catheters and breast implant infections, with varying antibiotic recalcitrance profiles. The ethanolic and methanolic extracts from P. oceanica rhizome exhibited significant antibacterial activity against E. faecalis and S. aureus, as well as drug resistant S. aureus clinical isolates. Furthermore, significant antibiofilm activity was observed against S. aureus and E. faecalis treated with ER, MR1, and MR2. P. oceanica extracts also exhibited synergistic antimicrobial activity with ciprofloxacin against E. faecalis, sensitizing E. faecalis to a lower ciprofloxacin concentration. Collectively, our data demonstrate the selective antibacterial and antibiofilm activity of the extracts of P. oceanica against Gram-positive bacteria and clinical isolates along with potentiation of current antibiotics, which suggests that P. oceanica can be further investigated as a potential source for novel therapeutic options in the treatment of drug resistant bacterial infections.

Efficacy of Nitrofurantoin and Fosfomycin against Extended Spectrum Beta Lactamase Producing Uropathogens in the Era of Antibiotic Resistance: A Cross-sectional Study

Background: Urinary Tract Infection (UTI) is one of the most common bacterial infections that require medical care. It accounts for 25% of all infections. Limited number of antibiotics are available for the treatment of UTI due to increased resistance among uropathogens. Aim of the study is to determine the causative agents of UTI and to evaluate the action of nitrofurantoin and fosfomycin against Enterobacteriaceae in ESBL (Extended spectrum beta-lactamase) producing strains. Material and Methods: It is a retrospective study carried out in the department of Microbiology, MAMC, Agroha. Data related to urine culture and antibiotic susceptibility pattern from January 2023 to December 2023 was taken from the records and analysed. Results: Out of 1648 urine samples processed, 569 showed significant bacterial growth. Escherichia coli (45.3%) was the most common isolate followed by Klebsiella pneumoniae (20.5%), Enterococcus (17.2%), Staphylococcus aureus (5%). Among the gram negative bacilli, 40% were ESBL producers. These ESBL producing strains were 99% sensitive to Fosfomycin and 75% sensitive to Nitrofurantoin. Conclusion: The study revealed that Nitrofurantoin and Fosfomycin are very effective oral drugs for empirical treatment against gram negative uropathogens causing UTI, especially multi drug resistant strains.

Probiotics in Dermatology: An Evidence-based Approach.

Probiotics are viable microorganisms that confer health benefits when administered to the host in adequate amounts. Over the past decade, there has been a growing demand for the use of oral and topical probiotics in several inflammatory conditions such as atopic dermatitis, psoriasis, acne vulgaris, etc., although their role in a few areas still remains controversial. The objective of this article is to shed light on understanding the origin and implications of microbiota in the pathophysiology of these dermatological conditions and the effect of probiotic usage. We have conducted a comprehensive search of the literature across multiple databases (PubMed, EMBASE, MEDLINE, and Google Scholar) on the role of probiotics in dermatological disorders. Commensal microbes of the skin and gastrointestinal tract play an important role in both health and disease. Increased use of probiotics has asserted a good safety profile, especially in this era of antibiotic resistance. With the advent of new products in the market, the indications, mechanism of action, efficacy, and safety profile of these agents need to be validated. Further studies are required. Oral and topical probiotics may be tried as a treatment or prevention modality in cutaneous inflammatory disorders, thus facilitating decreased requirement for topical or systemic steroids and antimicrobial agents. Tempering microbiota with probiotics is a safe and well-tolerated approach in this era of antimicrobial resistance.

Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing.

Phage therapy for burn wound infections in the era of antibiotic resistance

Infection of burn wounds caused by antibiotic-resistant pathogens is the leading cause of systemic infectious complications in burned patients and a key link in the pathogenesis of burn disease, causing its course and outcome. The use of phage therapy to overcome antibiotic resistance of infection agents is a promising direction, the development of which can improve the results of treatment of burned. The article discusses: 1) features of the infectious process in burned; 2) the effect of antibacterial chemotherapy of burn wound infection on the microbiome and the processes of reparative regeneration; 3) principles of phage therapy; 4) ways of delivering bacteriophages; 5) development of resistance to bacteriophages 6) personalization of phage therapy.

Antimicrobial therapy based on self-assembling peptides.

The emergence of drug-resistant microorganisms has threatened global health, and microbial infections have severely limited the use of medical materials. For example, the attachment and colonization of pathogenic bacteria to medical implant materials can lead to wound infections, inflammation and complications, as well as implant failure, shortening their lifespan and even resulting in patient death. In the era of antibiotic resistance, antimicrobial drug discovery needs to prioritize unconventional therapies that act on new targets or adopt new mechanisms. In this regard, supramolecular antimicrobial peptides have emerged as attractive therapeutic platforms, both as bactericides for combination antibiotics and as delivery vehicles. By taking advantage of their programmable intermolecular and intramolecular interactions, peptides can be modified to form higher-order structures (including nanofibers and nanoparticles) with unique functionality. This paper begins with an analysis of the relationship between peptide self-assembly and antimicrobial activity, describes in detail the research and development of various self-assembled antimicrobial peptides in recent years, and finally explores different combinatorial strategies for self-assembling antimicrobial peptides.

Clinical and antimicrobial susceptibility profile of typhoid fever in children in the era of antibiotic resistance.

Enteric fever remains a significant public health problem in low- and middle-income countries with further challenges from emerging antimicrobial resistance. Our prospective study evaluated the current clinical and antimicrobial susceptibility profile of enteric fever in 88 children and compared it to previously established literature. Enteric fever usually presents with nonspecific signs and symptoms, with predominant respiratory complaints. A paradigm shift in the antimicrobial sensitivity pattern has been noted, with increasing resistance for first-line antibiotics and older antibiotics such as ampicillin, cotrimoxazole, and chloramphenicol showing good sensitivity. Thus, the introduction of the latter merits consideration.

Diagnosis and Treatment of Helicobacter pylori Infection in Real Practice-New Role of Primary Care Services in Antibiotic Resistance Era.

Helicobacter pylori (H. pylori) is a key agent in several upper gastrointestinal diseases. Treatment of H. pylori infection is the main strategy for resolving the associated gastroduodenal damage in infected patients and for the prevention of gastric cancer development. Infection management is becoming complex due to the increase in antibiotic resistance, which already represents a global healthcare problem. Resistance to clarithromycin, levofloxacin or metronidazole have forced the adaptation of eradication regimens in this new reality to reach the eradication rate target recommended in most international guidelines (>90%). In this challenging scenario, molecular methods are revolutionizing the diagnosis of antibiotic-resistant infections and the detection of antibiotic resistance and opening a path towards personalized treatments, although their use is not yet widespread. Moreover, the infection management by physicians is still not adequate, which contributes to aggravating the problem. Both gastroenterologists and mainly primary care physicians (PCPs), who currently routinely manage this infection, perform suboptimal management of the diagnosis and treatment of H. pylori infection by not following the current consensus recommendations. In order to improve H. pylori infection management and to increase PCPs' compliance with guidelines, some strategies have been evaluated with satisfactory results, but it is still necessary to design and evaluate new different approaches.

Comparison of the effect of zinc oxide nanoparticles and extract of Acorus calamus applied topically on surgical wounds inflicted on the skin of rabbits.

Antibiotics are used for postsurgical wound healing purposes but unfortunately, resistance against them demands some alternatives for quick recovery. Sepsis of wounds is a challenge for medical as well as veterinary professionals. Nanoparticles have significant advantages in wound treatment and drug resistance reversal. This study was conducted to appreciate emerging alternates of antibiotics like zinc oxide nanoparticles and plant extracts in topical application. Zinc oxide is considered a good wound healer and its nanoparticles are easy to access. So, the efficacies of zinc oxide nanoparticles and sweet flag plant extract ointments were tested to compare modern and traditional therapeutics as sweet flag is considered a pure medicinal plant. Rabbits were selected for this study due to the healing properties of their skin. Wounds were inflicted on the thoracolumbar region and treated for 29 days post-surgically daily with normal saline and the ointment of zinc oxide nanoparticles and sweet flag extract ointment, prepared in a hydrophilic solvent. Wound shrinkage was observed daily and histopathological analysis was made and results were compared. Zinc oxide nanoparticles ointment showed the most satisfactory results for every parameter included in the study. No side effects of its topical application were observed. Healing was normal without any complications. The preparations of zinc oxide nanoparticles may help in the era of antibiotic resistance as topical drugs in the future.

Presence of potent inhibitors of bacterial biofilm associated proteins is the key to Citrus limon’s antibiofilm activity against pathogenic Escherichia coli

In an era of antibiotic resistance where natural antibiotic substitutes are considered essential, the antimicrobial and antibiofilm activities of Citrus limon extract on strains of pathogenic Escherichia coli isolated from pork were evaluated. The strains which form biofilms were more resistant (MIC50 = 2.5 mgml−1) compared to non-biofilm forming strains (MIC50 = 1.25 mgml−1). Use of C. limon extract at 20 mgml−1 concentration has resulted in inhibition of biofilm formation by 53.96%. Cyclobarbital, 5, 8-dimethoxycumarin, orotic acid and 3-methylsalicylhydrazide were the major phytochemicals in C. limon extract with highest docking affinities against the biofilm associated proteins in E. coli. The results of simulation studies have clearly illustrated the energy stability of the protein-ligand complexes. Absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles revealed that the phytochemicals in C. limon could be used in the drug design studies to preferentially target the specific receptors to combat biofilms associated with E. coli.

Carbonic Anhydrase Inhibitors as Novel Antibacterials in the Era of Antibiotic Resistance: Where Are We Now?

Resistance to antibiotic treatment developed by bacteria in humans and animals occurs when the microorganisms resist treatment with clinically approved antibiotics. Actions must be implemented to stop the further development of antibiotic resistance and the subsequent emergence of superbugs. Medication repurposing/repositioning is one strategy that can help find new antibiotics, as it speeds up drug development phases. Among them, the Zn2+ ion binders, such as sulfonamides and their bioisosteres, are considered the most promising compounds to obtain novel antibacterials, thus avoiding antibiotic resistance. Sulfonamides and their bioisosteres have drug-like properties well-known for decades and are suitable lead compounds for developing new pharmacological agent families for inhibiting carbonic anhydrases (CAs). CAs are a superfamily of metalloenzymes catalyzing the reversible reaction of CO2 hydration to HCO3- and H+, being present in most bacteria in multiple genetic families (α-, β-, γ- and ι-classes). These enzymes, acting as CO2 transducers, are promising drug targets because their activity influences microbe proliferation, biosynthetic pathways, and pathogen persistence in the host. In their natural or slightly modified scaffolds, sulfonamides/sulfamates/sulamides inhibit CAs in vitro and in vivo, in mouse models infected with antibiotic-resistant strains, confirming thus their role in contrasting bacterial antibiotic resistance.

Molecular Mechanism of Chloramphenicol and Thiamphenicol Resistance Mediated by a Novel Oxidase, CmO, in Sphingomonadaceae.

Antibiotic resistance mediated by bacterial enzyme inactivation plays a crucial role in the degradation of antibiotics in the environment. Chloramphenicol (CAP) resistance by enzymatic inactivation comprises nitro reduction, amide bond hydrolysis, and acetylation modification. However, the molecular mechanism of enzymatic oxidation of CAP remains unknown. Here, a novel oxidase gene, cmO, was identified and confirmed biochemically. The encoded CmO oxidase could catalyze the oxidation at the C-1' and C-3' positions of CAP and thiamphenicol (TAP) in Sphingobium sp. strain CAP-1. CmO is highly conserved in members of the family Sphingomonadaceae and shares the highest amino acid similarity of 41.05% with the biochemically identified glucose methanol choline (GMC) oxidoreductases. Molecular docking and site-directed mutagenesis analyses demonstrated that CAP was anchored inside the protein pocket of CmO with the hydrogen bonding of key residues glycine (G) 99, asparagine (N) 518, methionine (M) 474, and tyrosine (Y) 380. CAP sensitivity tests demonstrated that the acetyltransferase and CmO could enable a higher level of resistance to CAP than the amide bond-hydrolyzing esterase and nitroreductase. This study provides a better theoretical basis and a novel diagnostic gene for understanding and assessing the fate and resistance risk of CAP and TAP in the environment. IMPORTANCE Rising levels of antibiotic resistance are undermining ecological and human health as a result of the indiscriminate usage of antibiotics. Various resistance mechanisms have been characterized-for example, genes encoding proteins that degrade antibiotics-and yet, this requires further exploration. In this study, we report a novel gene encoding an oxidase involved in the inactivation of typical amphenicol antibiotics (chloramphenicol and thiamphenicol), and the molecular mechanism is elucidated. The findings provide novel data with which to understand the capabilities of bacteria to tackle antibiotic stress, as well as the complex function of enzymes in the contexts of antibiotic resistance development and antibiotic removal. The reported gene can be further employed as an indicator to monitor amphenicol's fate in the environment, thus benefiting risk assessment in this era of antibiotic resistance.

Bacteriophage Therapy in Implant-Related Orthopedic Infections.

Biofilm producers pose a major challenge in treating implant-related orthopedic infections (IROIs). The incidence of IROIs for the closed fracture amounts to 1% to 2% whereas for open fracture it is up to 30%. Due to inappropriate and irrational use of antibiotics in the management of infections, there is an emergence of a global "antimicrobial resistance crisis". To combat these antimicrobial resistance crises, a few innovative and targeted therapies like nanomedicine, phage therapy, antimicrobial peptides, and sonic therapies have been introduced. In this review, we have detailed the basic mechanisms involved in the employment of bacteriophage therapy for IROIs, along with the preclinical and clinical data on its utility. We also present the guidelines on its regulation, processing, and limitations of bacteriophage therpay to combat the upcoming era of antibiotic resistance.

Susceptibility Pattern of Blood Stream Infections in Neonatal Sepsis: Striking Alarm in Era of Antibiotic Resistance

Neonatal blood stream infections are significantly associated with increased morbidity and mortality in the recent years. In this study, we aim to determine the bacteriological profile and antibiotic susceptibility pattern of culture positive neonatal sepsis in the NICU of a tertiary teaching hospital in Kolkata. This retrospective study was conducted in the Department of Microbiology of a tertiary care teaching hospital in Kolkata between August, 2020 to July, 2021. All the neonates [both inborn / out born] admitted to NICU with the clinical diagnosis of sepsis during the specified period were screened for BSI. The blood was cultured in BACTAlert and analysed by VITEK 2. Out of 200 neonates with sepsis, 30 had culture positive sepsis of which 60% were Gram positive, rest were Gram negative. Staphylococcus aureus and Coagulase negative Staphylococcus (CoNS) were predominant (35.2%), Klebsiella was the predominant Gram negative organisms. Babies with birth weight ≤ 2 kg and gestational age 33 to 37 weeks were affected. Mortality was seen in 36.3% babies. Significant proportion of multidrug resistant isolates posed a great threat to neonatal survival. Hence modification of therapy based on anti-microbial surveillance pattern of the Institution with implementation of proper escalation and de-escalation of therapy is warranted. Keywords: antibiotic resistance, blood stream infections, culture positive sepsis

BIDding on PROTACs in an era of antibiotic resistance.

BIDding on PROTACs in an era of antibiotic resistance.