Resistant Pathogens Research Articles

Spectroscopic investigations of green synthesized zinc oxide nanoparticles (ZnO NPs): antioxidant and antibacterial activity

In the recent decade, zinc oxide nanoparticles (ZnO NPs) have been widely explored owing to their versatile properties and prodigious demands in the drug delivery, medical, energy storage, cosmetics, and the healthcare sectors. Therefore, the current work opts for an environmentally benign method to prepare ZnO NPs. The leaf extract of Calendula officinalis L. acts as a reducing agent for the metal ions; therefore, in the current research, ZnO NPs were prepared via green route by using Calendula officinalis leaf extract. Furthermore, the ZnO NPs were analysed with different spectroscopic techniques to confirm the structure and stability of nanomaterials. The prepared ZnO NPs were characterized by XRD, FE-SEM, FT-IR and UV–Vis studies. Also, the antioxidant and antimicrobial properties of the synthesized ZnO NPs were investigated. The XRD result of synthesized ZnO NPs showed the crystalline size 28.23 nm with wurtzite hexagonal structure along with the most intense peak (101). Following preliminary confirmations of the intended ZnO NPs, both big and small agglomerated forms were observed in the FE-SEM, which is often used to determine their exterior assembly. Further, the results of Fourier transform infrared spectroscopy (FT-IR) indicated the formation of pure ZnO NPs with an absorption peak of the Zn–O bond between 4000 cm−1 and 500 cm−1 and no discernible peak in the monitoring range. The UV–Vis spectrum of the green synthesized ZnO NPs were revealed two prominent absorption peaks at 355 nm and 370 nm with energy band gap of 2.986 eV. Using the 1, 1-di phenyl-2-picrylhydrazyl (DPPH) test, the antioxidant activity of the described ZnO NPs was assessed. It demonstrated how, ZnO NPs significantly increased their antioxidant activity by scavenging 1, 1-di phenyl-2-picrylhydrazyl (DPPH) free radicals. It could be seen that synthesis of the naturally occurring plant product ZnO NPs have been acting as an alternate of chemical antioxidant. The antimicrobial analysis was also performed with the help of disk diffusion method where three multi-drug resistant human pathogens namely Staphylococcus aureus, Klebsiella pneumoniae and E.coli were used. The Zone of Inhibition diameter values are 35.2 mm ± 0.9, 23.6 mm ± 0.1 and 13.5 mm ± 0.1, respectively, which showed that the ZnO NPs was highly effective against S. aureus. Thus, the green synthesis method of ZnO NPs using leaf extract of Calendula officinalis is evidence that it is superior and environmentally friendly method for the preparation of ZnO NPs and hence it can be utilized in various nano-medicine approaches.

Assessment of Published Papers on the Use of Machine Learning in Diagnosis and Treatment of Mastitis

The present study is an evaluation of published papers on machine learning as employed in mastitis research. The aim of this study was the quantitative evaluation of the scientific content and the bibliometric details of these papers. In total, 69 papers were found to combine machine learning in mastitis research and were considered in detail. There was a progressive yearly increase in published papers, which originated from 23 countries (mostly from China or the United States of America). Most original articles (n = 59) referred to work involving cattle, relevant to mastitis in individual animals. Most articles described work related to the development and diagnosis of the infection. Fewer articles described work on the antibiotic resistance of pathogens isolated from cases of mastitis and on the treatment of the infection. In most studies (98.5% of published papers), supervised machine learning models were employed. Most frequently, decision trees and support vector machines were employed in the studies described. ‘Machine learning’ and ‘mastitis’ were the most frequently used keywords. The papers were published in 39 journals, with most frequent publications in Computers and Electronics in Agriculture and Journal of Dairy Science. The median number of cited references in the papers was 39 (interquartile range: 31). There were 435 co-authors in the papers (mean: 6.2 per paper, median: 5, min.–max.: 1–93) and 356 individual authors. The median number of citations received by the papers was 4 (min.–max.: 0–70). Most papers (72.5%) were published in open-access mode. This study summarized the characteristics of papers on mastitis and artificial intelligence. Future studies could explore using these methodologies at farm level, and extending them to other animal species, while unsupervised learning techniques might also prove to be useful.

Next-Generation strategies to combat antimicrobial resistance: Integrating genomics, CRISPR, and novel therapeutics for effective treatment

Antimicrobial resistance (AMR) poses a significant threat to global public health, necessitating innovative strategies to combat this escalating issue. This review outlines next-generation approaches integrating genomics, CRISPR technology, and novel therapeutics to effectively address AMR. Genomic techniques enable comprehensive understanding of the genetic mechanisms underpinning resistance, facilitating the development of targeted interventions. By sequencing the genomes of resistant pathogens, researchers can identify resistance genes, track their spread, and predict emerging resistance patterns. CRISPR-Cas systems offer a revolutionary tool for combating AMR through precise genome editing. This technology can disrupt resistance genes, restore antibiotic sensitivity, and develop bacteriophage therapies that selectively target resistant bacteria. Moreover, CRISPR-based diagnostics enable rapid, accurate detection of resistant strains, enhancing infection control measures. The advent of novel therapeutics, such as antimicrobial peptides, bacteriophage therapy, and synthetic biology-derived compounds, provides alternative treatment options. These therapeutics can bypass traditional resistance mechanisms and exhibit efficacy against multi-drug resistant organisms. Additionally, integrating artificial intelligence (AI) and machine learning with genomics and CRISPR can accelerate the discovery of new antibiotics and predict resistance trends, optimizing treatment regimens. Implementing these next-generation strategies requires robust global collaboration, regulatory frameworks, and investment in research and development. By combining genomics, CRISPR, and novel therapeutics, we can create a multifaceted approach to overcome AMR, ensuring effective treatments and safeguarding public health. This integration represents a paradigm shift in antimicrobial strategy, offering hope for a future where resistant infections can be effectively managed and treated. Keywords: Integrating Genomics, Antimicrobial Resistance, CRISPR, Therapeutic

A comprehensive review on epigenetic and epitranscriptomic-mediated regulation of antibiotic resistance

Antibiotic resistance is the leading cause of death globally, with a higher possibility of the emergence of highly resistant pathogens, leading to epidemics. Several antibiotic resistance mechanisms have been discovered, such as enhanced efflux of antibiotics, reduced influx of antibiotics, alteration of antibiotics or their targets, and adaptation to antibiotics. However, this mechanism cannot fully explain the development of antibiotic resistance because the genes associated with this mechanism have been elucidated. However, the factors governing their regulation are not yet fully understood. Recent studies have highlighted the epigenetic and epitranscriptomic roles of antibiotic resistance development-associated genes. Epigenetic modification is associated with DNA modification, whereas epitranscriptomic modification is associated with RNA modification to control gene expression by regulating various biological phenomena such as splicing, translation, and stability. Therefore, this review will focus on the discovery of epigenetic modifications, particularly by DNA methyltransferases, such as restriction-modification (R-M) systems associated with methyltransferases, orphan DNA methyltransferases, and nucleoid-associated proteins that contribute to the development of antibiotic resistance. This scrutinization further expands to epitranscriptomic modification of non-coding RNA, which has a role in the regulation of antibiotic resistance. Epitranscriptomic modification of ribosomal RNA (rRNA), which is a major target of antibiotics, has been well explored. while non-coding RNA such as cis and trans small non coding RNA, and riboswitches are poorly explored. This epigenetic and epitranscriptomic modification will help to understand the regulation of antibiotic resistance-associated genes, which will help to identify key regulators of antibiotic resistance, paving the way for new antibiotic discovery, leading to decreased antibiotic mortality globally.

Microbiological profile of patients with orthopedic implant-associated infection in the post-COVID period

Background. The etiological structure of implant-associated infection and antibiotic resistance of pathogens are important when choosing empirical antibiotic therapy. COVID-19 pandemic and increased consumption of antibiotics by the population could provoke an increase in antibiotic resistance.The aim of the work. To compare the spectrum of leading pathogens of implantassociated infection in the pre- and post-Covid period and to assess antibiotic resistance.Materials and methods. A continuous retrospective study of biomaterial samples from traumatology and orthopedic patients with implant-associated infection was carried out for 2018–2019 and 2021–2022. The sample consisted of 548 microorganism strains (n = 237 and n = 317, respectively) in 442 cases of infectious complications. The antibiotic resistance of all isolated microorganisms, including those from microbial associations, was assessed.Results. The leading pathogen of monomicrobial implant-associated infection in both study periods was Staphylococcus epidermidis (33–37 %). In 2021–2022, the proportion of microbial associations increased (from 12.5 to 17.5 %; p = 0.147) with the appearance of fungi in the microbial landscape. In the post-Covid period, the increase in Staphylococcus aureus resistance to tetracycline and doxycycline was revealed; the isolation of methicillin-resistant strains among Staphylococcus aureus decreased from 4 cases (out of 187) to 3 (out of 232); 100 % sensitivity to rifampicin and co-trimoxazole was maintained. An increase in Staphylococcus epidermidis resistance to all tested antibiotics was detected (statistically significant increase in resistance to fluoroquinolones; p = 0.002–0.003) with the isolation of methicillin-resistant strains in 80.5% and 80.9% of cases, respectively. All staphylococcal isolates were susceptible to vancomycin and linezolid. Enterobacteriaceae representatives showed a decrease in resistance to carbapenems and an increase in resistance to co-trimoxazole; in Pseudomonas aeruginosa and Acinetobacter baumannii, there is an increase in resistance to carbapenems and fluoroquinolones. All gram-negative microorganisms were sensitive to colistin.Conclusion. The high frequency of isolation of methicillin-resistant staphylococci determines the choice of vancomycin for empirical therapy. Increasing resistance of staphylococci to fluoroquinolones may limit their use. Increasing resistance of gram-negative bacteria and a narrow spectrum of antibiotics acting on carbapenemase producers may reduce the effectiveness of therapy.

HLH-30/TFEB mediates sexual dimorphism in immunity in Caenorhabditis elegans

ABSTRACT Sexual dimorphism affects various biological functions, including immune responses. However, the mechanisms by which sex alters immunity remain largely unknown. Using Caenorhabditis elegans as a model species, we showed that males exhibit enhanced immunity against various pathogenic bacteria through the upregulation of HLH-30 (Helix Loop Helix 30/TFEB (transcription factor EB)), a transcription factor crucial for macroautophagy/autophagy. Compared with hermaphroditic C. elegans, males displayed increased activity of HLH-30/TFEB, which contributed to enhanced antibacterial immunity. atg-2 (AuTophaGy (yeast Atg homolog) 2) upregulated by HLH-30/TFEB mediated increased immunity in male C. elegans. Thus, the males appear to be equipped with enhanced HLH-30/TFEB-mediated autophagy, which increases pathogen resistance, and this may functionally prolong mate-searching ability with reduced risk of infection. Abbreviations: atg-2: AuTophaGy (yeast Atg homolog) 2; FUDR: 5-fluoro-2’-deoxyuridine; GSEA: gene set enrichment analysis; HLH-30: Helix Loop Helix 30; LC3: microtubule associated protein 1 light chain 3; NGM: nematode growth media; RNA-seq: RNA sequencing; SEM: standard error of the mean; TFEB: transcription factor EB; WT: wild-type

Antibiotics, Analgesic Sedatives, and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review.

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety. Important obstacles contributing to inadequate studies in preterm/sick infants include difficulties in obtaining parental consent, physicians' unwillingness to recruit preterm infants, the off-label use of many medications in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials (antifungals), analgesics (sedatives), and antiseizure medications in neonates, focusing on current evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage, and evidence-based guidelines for their optimal use in neonates. We also address the effects of early antibiotic use on the intestinal microbiome and its association with long-term immune-related diseases, obesity, and neurodevelopment (ND). Recommendations for empirical treatment and the emergence of pathogen resistance to antimicrobials and antifungals are also presented. Finally, future perspectives on the prevention, modification, or reversal of antibiotic resistance are discussed.

From Species to Genes: A New Diagnostic Paradigm.

Molecular diagnostics has the potential to revolutionise the field of clinical microbiology. Microbial identification and nomenclature have, for too long, been restricted to phenotypic characterisation. However, this species-level view fails to wholly account for genetic heterogeneity, a result of lateral gene transfer, mediated primarily by mobile genetic elements. This genetic promiscuity has helped to drive virulence development, stress adaptation, and antimicrobial resistance in several important bacterial pathogens, complicating their detection and frustrating our ability to control them. We argue that, as clinical microbiologists at the front line, we must embrace the molecular technologies that allow us to focus specifically on the genetic elements that cause disease rather than the bacterial species that express them. This review focuses on the evolution of microbial taxonomy since the introduction of molecular sequencing, the role of mobile genetic elements in antimicrobial resistance, the current and emerging assays in clinical laboratories, and the comparison of phenotypic versus genotypic analyses. In essence, it is time now to refocus from species to genes as part of a new diagnostic paradigm.

Ripening and rot: How ripening processes influence disease susceptibility in fleshy fruits.

Fleshy fruits become more susceptible to pathogen infection when they ripen; for example, changes in cell wall properties related to softening make it easier for pathogens to infect fruits. The need for high-quality fruit has driven extensive research on improving pathogen resistance in important fruit crops such as tomato (Solanum lycopersicum). In this review, we summarize current progress in understanding how changes in fruit properties during ripening affect infection by pathogens. These changes affect physical barriers that limit pathogen entry, such as the fruit epidermis and its cuticle, along with other defenses that limit pathogen growth, such as preformed and induced defense compounds. The plant immune system also protects ripening fruit by recognizing pathogens and initiating defense responses involving reactive oxygen species production, mitogen-activated protein kinase signaling cascades, and jasmonic acid, salicylic acid, ethylene, and abscisic acid signaling. These phytohormones regulate an intricate web of transcription factors (TFs) that activate resistance mechanisms, including the expression of pathogenesis-related genes. In tomato, ripening regulators, such as RIPENING INHIBITOR and NON_RIPENING, not only regulate ripening but also influence fruit defenses against pathogens. Moreover, members of the ETHYLENE RESPONSE FACTOR (ERF) family play pivotal and distinct roles in ripening and defense, with different members being regulated by different phytohormones. We also discuss the interaction of ripening-related and defense-related TFs with the Mediator transcription complex. As the ripening processes in climacteric and non-climacteric fruits share many similarities, these processes have broad applications across fruiting crops. Further research on the individual contributions of ERFs and other TFs will inform efforts to diminish disease susceptibility in ripe fruit, satisfy the growing demand for high-quality fruit and decrease food waste and related economic losses.

Mycoplasma genitalium Infections Among Participants in an HIV Pre-exposure Prophylaxis Program in Hanoi, Vietnam.

Mycoplasma genitalium causes a sexually transmitted infection and is also emerging as an important antimicrobial resistant pathogen. Data on M. genitalium infections among men who have sex with men (MSM) in low-resource settings are sparse. From January to December 2022, participants in an HIV pre-exposure prophylaxis (PrEP) program in Hanoi, Vietnam were enrolled into the study. Demographic, behavioral, and clinical characteristics were collected. Self-collected urine, rectal, and pharyngeal specimens were tested for M. genitalium using the Alinity m STI Assay (Abbott Molecular, USA). Univariate and multivariate logistic regression were performed to assess for factors associated with infections. Among 477 participants, the median age was 25.3 years (21.7-29.6) and 92.2% (n = 440) identified as MSM; 48.6% had ≥2 sex partners and 38.1% reported condomless anal sex in the prior month. The overall prevalence of M. genitalium infection was 10.9% (52/477); 7.3% (34/464) rectal, 3.2% (15/476) urethral, and 1.9% (9/476) pharyngeal. Infections were asymptomatic in 71.2% (37/52). Among those with M. genitalium , 30.7% (16/52) were co-infected with either Neisseria gonorrhoeae or Chlamydia trachomatis. Among those reporting rectal (n = 51) or urethral (n = 35) symptoms, but without C. trachomatis or N. gonorrhoeae co-infections, five (9.8%) had rectal infections and one (2.9%) had urethral infection. Participants with M. genitalium were more likely to be asymptomatic than participants without M. genitalium (adjusted odds ratio, 1.93; 95% confidence interval, 1.01-3.71). Mycoplasma genitalium infections were common among primarily MSM engaged in an HIV PrEP program in Vietnam. The prevalence was highest in rectal specimens and nearly three quarters of M. genitalium infections were asymptomatic. Testing for M. genitalium infections among those with symptoms is important to enable pathogen-directed therapy. Additional research on antimicrobial resistance and treatment strategies for M. genitalium in low-resource settings is needed.

Altering Microbial Communities in Substrate to Stimulate the Growth of Healthy Button Mushrooms

Green mould, caused by Trichoderma aggressivum, is one of the major fungal diseases of button mushrooms. The main problems in chemical disease control include a lack of effective agents, the occurrence of pathogen resistance to pesticides, and the harmful impact on the environment. In an attempt to find a solution, the interaction between two beneficial microorganisms, Bacillus amyloliquefaciens B-241 (an antifungal agent) and Streptomyces flavovirens A06 (a yield stimulant), was investigated in vivo. The synergy factor (SF) was calculated as a ratio between the observed and expected impact on the yield or efficacy of disease suppression after artificial inoculation with T. aggressivum. The highest control of T. aggressivum was achieved by joint application of the two beneficial microorganisms. The additive interaction between microorganisms in efficacy against the pathogen was revealed. The largest yield was obtained in mushroom beds sprayed with the two beneficial microorganisms combined (B-241 80% and A06 20%). Regarding the impact on the yield, synergistic interaction between the two microorganisms was confirmed (SFs were 1.62 or 1.52). The introduction of optimized microbial combinations could create new possibilities for biorational edible mushroom protection, with improved yield and quality and reduced risks to human health and the environment.

Trichophyton indotineae: first case in Ireland and response to topical Griseofulvin.

To our knowledge, we report the first case of Trichophyton indotineae in Ireland, highlighting the pathogen’s resistance to conventional antifungal treatments and the necessity for advanced diagnostic techniques. Notably, the infection in our patient began to resolve when griseofulvin liquid was unintentionally used topically, suggesting an alternative treatment approach for this resistant dermatophyte.

Quantitative Prediction of Human Immunodeficiency Virus Drug Resistance.

Drug resistance of pathogens, including viruses, is one of the reasons for decreased efficacy of therapy. Considering the impact of HIV type 1 (HIV-1) on the development of progressive immune dysfunction and the rapid development of drug resistance, the analysis of HIV-1 resistance is of high significance. Currently, a substantial amount of data has been accumulated on HIV-1 drug resistance that can be used to build both qualitative and quantitative models of HIV-1 drug resistance. Quantitative models of drug resistance can enrich the information about the efficacy of a particular drug in the scheme of antiretroviral therapy. In our study, we investigated the possibility of developing models for quantitative prediction of HIV-1 resistance to eight protease inhibitors based on the analysis of amino acid sequences of HIV-1 protease for 900 virus variants. We developed random forest regression (RFR), support vector regression (SVR), and self-consistent regression (SCR) models using binary vectors containing values from 0 or 1, depending on the presence of a specific peptide fragment in each amino acid sequence as independent variables, while fold ratio, reflecting the level of resistance, was the predicted variable. The SVR and SCR models showed the highest predictive performances. The models built demonstrate reasonable performances for eight out of nine (R2 varied from 0.828 to 0.909) protease inhibitors, while R2 for predicting tipranavir fold ratio was lower (R2 was 0.642). We believe that the developed approach can be applied to evaluate drug resistance of molecular targets of other viruses where appropriate experimental data are available.

Antimicrobial Face Masks and Mask Covers with a Salt-Coated Stacked Spunbond Polypropylene Fabric: Effective Inactivation of Resilient Pathogens and Prevention of Contact Transmission.

In response to the ongoing threat posed by respiratory diseases, ensuring effective transmission protection is crucial for public health. To address the drawbacks of single-use face masks/respirators, which can be a potential source of contact-based transmission, we have designed an antimicrobial face mask and mask covering utilizing a stack of salt-coated spunbond (SB) fabric. This fabric acts as an outer layer for the face mask and as a covering over a conventional mask, respectively. We evaluated the universal antimicrobial performance of the salt-coated three-stacked SB fabric against enveloped/nonenveloped viruses and spore-forming/nonspore-forming bacteria. The distinctive pathogen inactivation efficiency was confirmed, including resistant pathogens such as human rhinovirus and Clostridium difficile. In addition, we tested other filter attributes, such as filtration efficiency and breathability, to determine the optimal layer for salt coating and its effects on performance. Our findings revealed that the outer layer of a conventional face mask plays a crucial role in contact transmission through contaminated face masks and respirators. Through contact transmission experiments using droplets involving three types of contaminants (fluorescent dyes, bacteria, and viruses), the salt-coated stacked SB fabric demonstrated a superior effect in preventing contact transmission compared to SB or meltblown polypropylene fabrics─an issue challenging to existing masks. Our results demonstrate that the use of salt-coated stacked SB fabrics as (i) the outer layer of a mask and (ii) a mask cover over a mask enhances overall filter performance against infectious droplets, achieving high pathogen inactivation and low contact-based transmission while maintaining breathability.

Genomic Insights into Bacterial Antimicrobial Resistance Transmission and Mitigation Strategies.

The rapid emergence and global spread of antimicrobial resistance in recent years have raised significant concerns about the future of modern medicine. Superbugs and multidrugresistant bacteria have become endemic in many parts of the world, raising the specter of untreatable infections. The overuse and misuse of antimicrobials over the past 80 years have undoubtedly contributed to the development of antimicrobial resistance, placing immense pressure on healthcare systems worldwide. Nonetheless, the molecular mechanisms underlying antimicrobial resistance in bacteria have existed since ancient times. Some of these mechanisms and processes have served as the precursors of current resistance determinants, highlighting the ongoing arms race between bacteria and their antimicrobial adversaries. Moreover, the environment harbors many putative resistance genes, yet we cannot still predict which of these genes will emerge and manifest as pathogenic resistance phenotypes. The presence of antibiotics in natural habitats, even at sub-inhibitory concentrations, may provide selective pressures that favor the emergence of novel antimicrobial resistance apparatus and, thus, underscores the need for a comprehensive understanding of the factors driving the persistence and spread of antimicrobial resistance. As the development of antimicrobial strategies that evade resistance is urgently needed, a clear perception of these critical factors could ultimately pave the way for the design of innovative therapeutic targets.

An Injectable Living Hydrogel with Embedded Probiotics as a Novel Strategy for Combating Multifaceted Pathogen Wound Infections.

Wound infections pose a significant challenge in healthcare, and traditional antibiotic treatments often result in the development of resistant pathogens. Addressing this gap, ProGel is introduced, a living hydrogel created by entrapping probiotic Lactobacillus plantarum as a therapeutic component within a gelatin matrix. With a double-syringe system, ProGel can be easily mixed and applied, conforming swiftly to any wound shape and forming hydrogel in situ. It also demonstrates robust mechanical and self-healing properties owing to the Schiff-base bonds. ProGel sustains more than 80% viability of the entrapped L. plantarum while restricting their escape from the hydrogel. After a week of storage, more than 70% viability of the entrapped L. plantarum is preserved. Importantly, ProGel exhibits broad-spectrum antimicrobial efficacy against pathogens commonly associated with wound infections, i.e., Pseudomonas aeruginosa (7Log reduction), Staphylococcus aureus (3-7Log reduction), and Candida albicans (40-70% reduction). Moreover, its cytocompatibility is affirmed through coculture with human dermal fibroblasts. The effectiveness of ProGel is further highlighted in more clinically relevant tests on human skin wound models infected with P. aeruginosa and S. aureus, where it successfully prevents the biofilm formation of these pathogens. This study showcases an injectable living hydrogel system for the management of complex wound infections.

New Agents Are Coming, and So Is the Resistance.

Antimicrobial resistance is a global threat that requires urgent attention to slow the spread of resistant pathogens. The United States Centers for Disease Control and Prevention (CDC) has emphasized clinician-driven antimicrobial stewardship approaches including the reporting and proper documentation of antimicrobial usage and resistance. Additional efforts have targeted the development of new antimicrobial agents, but narrow profit margins have hindered manufacturers from investing in novel antimicrobials for clinical use and therefore the production of new antibiotics has decreased. In order to combat this, both antimicrobial drug discovery processes and healthcare reimbursement programs must be improved. Without action, this poses a high probability to culminate in a deadly post-antibiotic era. This review will highlight some of the global health challenges faced both today and in the future. Furthermore, the new Infectious Diseases Society of America (IDSA) guidelines for resistant Gram-negative pathogens will be discussed. This includes new antimicrobial agents which have gained or are likely to gain FDA approval. Emphasis will be placed on which human pathogens each of these agents cover, as well as how these new agents could be utilized in clinical practice.

The Effectiveness of the Use of Collapse Therapy Methods and Bronchoblocation in the Complex Treatment of a Patient with Multidrug Resistance Pathogen: Clinical Observation

Currently, according to the World Health Organization, the targets for the effectiveness of treatment of patients with pulmonary tuberculosis do not achieve their goals. In this regard, it is urgent to search for optimal integrated approaches in the treatment of patients with pulmonary tuberculosis.The aim of the work is to demonstrate the high effectiveness of the use of methods of collapse therapy and CBB in the complex treatment of a patient with a widespread tuberculosis process.Materials and methods. The analysis of the patient’s medical documentation was carried out, the data of the anamnesis of the disease, the analysis of the X-ray archive, the data of clinical, laboratory and instrumental examinations were studied.Results. Multidrug resistance (MDR) of Mycobacterium tuberculosis (MBT) was established on the 1st day of hospitalization. Comprehensive treatment was carried out in full: chemotherapy according to the MDR-tuberculosis regimen, pneumoperitoneum for 8 months, CBB for 6 months.Discussion. The presented clinical example demonstrates that against the background of a significant decrease in immunity due to the severe course of viral pneumonia, previously undetected pulmonary tuberculosis has taken a progressive course. Due to the use of complex treatment in a patient with a widespread tuberculosis process, clinical improvement was achieved, the closure of massive decay cavities in lung tissue and resorption of focal infiltrative changes was radiologically achieved.Conclusion. A clinical example demonstrates the high effectiveness and safety of the use of collapse therapy methods in the complex treatment.

Complex vaccination strategies prevent the emergence of vaccine resistance.

Vaccination is the most effective tool to control infectious diseases. However, the evolution of vaccine resistance, exemplified by vaccine resistance in SARS-CoV-2, remains a concern. Here, we model complex vaccination strategies against a pathogen with multiple epitopes-molecules targeted by the vaccine. We found that a vaccine targeting one epitope was ineffective in preventing vaccine escape. Vaccine resistance in highly infectious pathogens was prevented by the full-epitope vaccine, that is, one targeting all available epitopes, but only when the rate of pathogen evolution was low. Strikingly, a bet-hedging strategy of random administration of vaccines targeting different epitopes was the most effective in preventing vaccine resistance in pathogens with the low rate of infection and high rate of evolution. Thus, complex vaccination strategies, when biologically feasible, may be preferable to the currently used single-vaccine approaches for long-term control of disease outbreaks, especially when applied to livestock with near 100% vaccination rates.

Potential mechanism of gallic acid-coated iron oxide nanoparticles against associated genes of Klebsiella pneumoniae capsule, antibacterial and antibiofilm.

Antibiotic resistance has increased in recent years, especially for pathogens like Klebsiella pneumoniae. Discovering and developing new drugs is challenging due to the high resistance of pathogens. Metal nanoparticles have been widely used in recent years to overcome and treat infections. Gallic acid-coated iron oxide nanoparticles (IONPs-GA) were synthesized in a simple and cost-effective method. The morphology characteristics of synthesized IONPs-GA were analyzed using Fourier transform infrared spectroscopy (FTIR), x-ray diffraction analysis (XRD), and scanning electron microscope (SEM) analysis. IONPs were mostly spherical in shape with sizes ranging between 32 and 61 nm. All analyses used in this study confirmed the successful coating of gallic acid to iron oxide. Biological activities were studied phenotypically and on the molecular level, including antibacterial, antibiofilm, and mRNA levels of capsule-associated genes. The results showed high antimicrobial activity of the synthesized nanoparticles against different G+ve and G-ve bacteria. The highest activity was recorded against Staphylococcus aureus (43 mm) and K. pneumoniae (22 mm). The MIC of IONPs against K. pneumoniae was 3.12 mg/mL and SEM analysis showed adhering the IONPs-GA to the cell surface of K. pneumoniae resulted in disrupting the cell membrane. Different concentrations of sub-MIC inhibited K. pneumoniae biofilm formation with the highest inhibition percentage at ½ × MIC (66.86%). Also, the synthesized IONPs-GA differently affected the regulation and mRNA level of capsule-associated genes in K. pneumoniae. The results indicated that IONPs-GA could be useful in biological applications such as in drug delivery and treatment wide range of pathogens. RESEARCH HIGHLIGHTS: Gallic acid was successfully coated into iron oxide nanoparticles synthesized in a simple way. IONPs-GA was morphologically characterized using FTIR, XRD, and SEM. Evaluation the activity of IONPs-GA as antibacterial, antibiofilm, and study the potential level of mRNA affected by IONPs-GA.