Multidrug-resistant Pathogens Research Articles

Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of Pseudomonas aeruginosa-infected lung inflammation.

Pseudomonas aeruginosa (PA) is one of the most common multidrug-resistant pathogens found in clinics, often manifesting as biofilms. However, due to the emergence of superbugs in hospitals and the overuse of antibiotics, the prevention and treatment of PA infections have become increasingly challenging. Utilizing DNA nanostructures for packaging and delivering antibiotics presents an intervention strategy with significant potential. Nevertheless, construction of functional DNA nanostructures with multiple functionalities and enhanced stability in physiological settings remains challenging. In this study, the authors propose a magnesium-free assembly method that utilizes tobramycin (Tob) as a mediator to assemble DNA nanostructures, allowing for the functionalization of DNA nanostructures by combining DNA and antibiotics. Additionally, our study incorporates maleimide-modified DNA into the nanostructures to act as a targeting moiety specifically directed towards the pili of PA. The targeting ability of the constructed functional DNA nanostructure significantly improves the local concentration of Tob, thereby reducing the side effects of antibiotics. Our results demonstrate the successful construction of a maleimide-decorated Tob/DNA nanotube (NTTob-Mal) for the treatment of PA-infected lung inflammation. The stability and biocompatibility of NTTob-Mal are confirmed, highlighting its potential for clinical applications. Furthermore, its specificity in recognizing and adhering to PA has been validated. In vitro experiments have shown its efficacy in inhibiting PA biofilm formation, and in a murine model, NTTob-Mal has exhibited significant therapeutic effectiveness against PA-induced pneumonia. In summary, the proposed antibiotic drug-mediated DNA nanostructure assembly approach holds promise as a novel strategy for targeted treatment of PA infections.

Lactoferrin impairs pathogen virulence through its proteolytic activity.

Antibiotics, often hailed as 'miracle drugs' in the 20th century, have revolutionised medicine by saving millions of lives in human and veterinary medicine, effectively combatting bacterial infections. However, the escalating global challenge of antimicrobial resistance and the appearance and spread of multidrug-resistant pathogens necessitates research into alternatives. One such alternative could be lactoferrin. Lactoferrin, an iron-binding multifunctional protein, is abundantly present in mammalian secretions and exhibits antimicrobial and immunomodulatory activities. An often overlooked aspect of lactoferrin is its proteolytic activity, which could contribute to its antibacterial activity. The proteolytic activity of lactoferrin has been linked to the degradation of virulence factors from several bacterial pathogens, impeding their colonisation and potentially limiting their pathogenicity. Despite numerous studies, the exact proteolytically active site of lactoferrin, the specific bacterial virulence factors it degrades and the underlying mechanism remain incompletely understood. This review gives an overview of the current knowledge concerning the proteolytic activity of lactoferrins and summarises the bacterial virulence factors degraded by lactoferrins. We further detail how a deeper understanding of the proteolytic activity of lactoferrin might position it as a viable alternative for antibiotics, being crucial to halt the spread of multi-drug resistant bacteria.

Antimicrobial Resistance: Interplay of Animal, Environment, Human and Coordinated Mitigation Strategies

Bacteria, viruses, fungi, and parasites are examples of microorganisms that exhibit resistance; in contrast, antibiotic resistance is exclusive to bacterial resistance. Antimicrobial resistance poses an escalating global threat to human health. The emergence of multidrug-resistant pathogens, resulting in compromised treatment efficacy and increased mortality rates poses a significant problem to global health. The transmission of antimicrobial resistant strains between humans and animals, particularly in close contact settings, underscores the necessity of a unified approach to one health and further blurs the boundaries between human and animal health. This article aims to highlight microbial resistance which are of significant clinical and epidemiologic importance. Environmental reservoirs, including water bodies and soil, serve as critical conduits for the transmission of antimicrobial resistant genes. Antimicrobial resistance is a complex dynamic within the interconnected realms of human, animal, and environmental health necessitating a comprehensive understanding of the subject matter. It is important to review the intricate interplay of these factors, as current evidence suggests, emphasising the urgent need for coordinated mitigation strategies to address the multifaceted challenges posed by antimicrobial resistance. This review provides insight on fostering interdisciplinary research which is critical for elucidating the intricate pathways of resistance transmission and for developing innovative interventions against antimicrobial resistance. The urgency of implementing coordinated and holistic mitigation strategies cannot be overstated, as the consequences of inaction extend beyond individual health sectors to encompass the broader fabric of global health security.

Antibacterial and anti-biofilm profiling of Syzygium Aro-Maticum Plant Extracts against Multi-drug resistant Human Pathogens

Due to rapidly propagating global resistance to antibiotics/pharmacological agents (One Health Challenge) and costly-expenditure for antibiotic formulation, it is primordial to look for efficient alternatives and ample of evidences document the ability of plant extracts in this regard. This study aimed to evaluate antibacterial and anti-biofilm profiles of Syzygium aromaticum extracts against multidrug-resistant (MDR) pathogens. Sampling of blood and urinary catheters was done from clinical laboratory of Multan Pakistan. A total of 06 pathogenic strains: Streptococcus pyogenes, Staphylococcus saprophyticus, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, were isolated and confirmed by 16SrRNA Ribotyping. Kirby-Bauer Disc Diffusion method was employed for resistance profiling. Flowers of S. aromaticum were used to prepare 04 different extracts i.e., Methanolic, Ethanolic, Dimethyl sulfoxide and Aqueous. Phytochemical screening showed all extracts positive for Proteins, Carbohydrates, Glycosides, Terpenoids, Saponins and Steroids. MIC and MBC value of all extracts was found 40 µg/ml and 160 µg/ml respectively except Methanolic extract (20 µg/ml and 80 µg/ml respectively). Highest anti-biofilm activity was seen for methanolic extracts. FRAP % was found directly proportional to extract concentration while DDPH % inhibition was: methanolic > ethanolic >Aqueous > DMSO extract. In TLC Analysis, highest Rf value was recorded for Methanolic extract. FTIR analysis showed different peaks as: Alkyl halide-698.58/cm, Aromatic group-879/cm, Alcohol-1013.63/cm, Polysaccharides-1045.10/cm, Carboxylic acid-1436.15/cm, Amides-1515.01/cm and Aldehydes/ketones-2975.35/cm. It is concluded that Methanolic extract of Syzygium aromaticum was found to have highest antibacterial, anti-biofilm and antioxidant potential thus its secondary metabolites are cost-effective candidates which can fuel the future pipeline for antibiotic discovery.

Phenotypic Resistance of (MRSA) Clinical Isolates to Some Macrolide Antibiotic Groups

Antimicrobial resistance is one of the most significant global threats to human health in recent times, and it limits the achievement of several of the sustainable development goals. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most essential multidrug-resistant bacterial pathogens. The study aimed to determine the prevalence of (MRSA) from different clinical samples to emphasise the suitable treatment. One hundred fifty different clinical samples were collected. All these samples were subjected to classical microbiological testing, which included culturing directly on mannitol salt agar and antibiotic susceptibility test (A.S.T). The results observed that only 32 out of 150 samples of MRSA isolates were identified using cefoxitin 30 (µg) as a screening antibiotic, as suggested by CLSI. These 32 MRSA isolates showed resistance toward penicillin and cefoxitin, high sensitivity against vancomycin, and moderate resistance against doxycycline and azithromycin. Considering the phenotyping resistance toward macrolide antibiotic groups, 10/32 (31.25%) showed S-phenotype,18/32 (52.65%) showed R-phenotype,4/32 (12.5%) showed D-phenotype while no MRSA isolated showed D+ phenotype. This study concludes that inducible clindamycin resistance of S. aureus (MRSA) increases the difficulty of treating S. aureus bacterial infections.

Investigation of Antimicrobial Susceptibility Patterns and blaVIM -metallo-β-lactamase Gene in Clinical Samples of Klebsiella pneumoniae

Multidrug resistance is a widespread issue that plays an important role in disease outcome. This study was designed to isolate Klebsiella pneumonia in different clinical specimens and detected their Antibiotic resistance profile. A total of 319 samples were collected from various clinical specimens for both genders and different ages. The samples were streaked on the blood and MacConkey agars. The bacterial growth identified using biochemical tests and Vitek®2 systems to confirm it. Also, the Vitek®2 system was used to detect the antibiotic sensitivity. Out of 319 clinical samples, K. pneumonia was identified in 67 (21%) cases. The highest isolation rate was in urine 25(37.3%), followed by sputum 13(19.4%), and the least isolation was in CSF with one isolate (1.5%). The results revealed that K. pneumonia isolates were multi-drug resistant pathogens (MDR) with high resistance to Ampicillin (97%) and 85% for piperacillin. The PCR results revealed blaVIM- genes frequency was 20 (30%). K. pneumonia is one of the bacteria that cause urinary tract infections, and it is a widespread multidrug-resistant pathogen, and blaVIM- producing K. pneumoniae are found in clinical samples at Thi-Qar hospitals. Therefore, monitoring the administration of antibiotics and their rational use is necessary to reduce antimicrobial resistance and treatment failure.

Phage-antibiotic synergism against Salmonella typhi isolated from stool samples of typhoid patients.

Typhoid fever is a fatal disease in humans that is caused by Salmonella typhi. S. typhi infections need immediate antibiotic therapy, and their extensive use has led to multidrug-resistant (MDR) pathogens. The use of bacteriophages is becoming a new way to treat these resistant bacteria. This research was directed to bacteriophage isolation against S. typhi and to determine phage-antibiotic synergism. To isolate bacteriophages targeting S. typhi, the causative agent of typhoid fever, and investigate their potential synergistic effects when combined with antibiotics. A cross-sectional study. The Widal test was positive; twenty diarrheal stool samples were taken, and for confirmation of S. typhi, different biochemical tests were performed. The disc-diffusion technique was used to determine antimicrobial resistance, and the double agar overlay method was used for bacteriophage isolation from sewage water against S. typhi. To test antibiotic-phage synergism, the S. typhi bacteria was treated by phages together with varying antibiotic concentrations. Eleven samples were positive for S. typhi with black colonies on SS-agar. These were catalase and MR positive with alkali butt on TSI. Clear plaques were observed after the agar overlay. Isolated phages were stable at various pH and temperature levels. Synergism was observed on agar plate. The zone was enlarged when phages were combined with bacterial lawn culture and ciprofloxacin disk. Bacterial growth inhibition had a significant p-value of 0.03 in titration plates, with the phage-ciprofloxacin combination being more effective than the phage and antibiotic alone. The study highlights the synergistic effects of isolated bacteriophages with antibiotics, which are not only effective against S. typhi infection but also decrease antibiotic resistance.

First report of Candida auris in Guangdong, China: clinical and microbiological characteristics of 7 episodes of candidemia

ABSTRACT Candida auris is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of C. auris candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All C. auris isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the ERG11 gene. The isolates with Clade I presented Y132F mutation in the ERG11 gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of C. auris candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of C. auris candidemia and colonization after the first positive bloodstream. C. auris colonization was still observed after the first C. auris candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of C. auris in Guangdong, highlighting great challenges in clinical prevention and control.

Unveiling the emergence of multidrug-resistant pathogens in exotic pets from France: a comprehensive study (2017-2019)

Aim: This study intends to assess the occurrence of multi-drug resistant (MDR) resistant pathogens among exotic pets from France (2017-2019). Methods: Isolates were identified using MALDI-TOF-MS. Antimicrobial susceptibility testing was conducted for 21 antimicrobials and was assayed by disk diffusion methods. Statistical analyses were carried out using GraphPad Prism® (version 9.4.1.). Results: Isolates (n = 2,100) recovered from samples of 10 small mammals (n = 1,555), 23 birds (n = 287), and 18 reptiles (n = 208) species were identified as Enterobacterales (n = 634), Pseudomonadaceae (n = 176), Pasteurellacea (n = 276), Staphylococcaceae (n = 563) , Streptococcaceae (n = 259), and Enterococcaceae (n = 186). Consistent high resistance rates were observed among diverse genera and/or species to beta-lactams, tetracyclines, and macrolides. Notably, a significant prevalence of MDR bacteria was identified, with 22.8% (n = 479/2,100, P < 0.05). Furthermore, 23.5% (P < 0.05) of these MDR bacteria displayed resistance to all tested antimicrobials: E. faecalis (n = 47/49; 95.0%), E. coli (n = 19/52; 36.5%), Klebsiella spp. (n = 12/32; 37.5%), S. epidermidis (n = 7/25; 28%), Streptococcus spp. (n = 6/68; 8.8%), Enterococcus spp. (n = 6/23; 26%), Staphylococcus spp. (n = 4/51; 7.8%), Lactococcus spp. (n = 4/8; 50%), Citrobacter spp. (n = 3/7; 42.8%), Raoultella spp. (n = 2/3; 66.6%), Serratia spp. (n = 1/9; 11.1%), Pasteurella spp. (n = 1/14; 7.1%), and S. xylosus (n = 1/28; 3.5%). Conclusions: This study emphasizes exotic pets as an emergent reservoir of MDR bacteria, focusing on E. faecalis as a potential route of transmission of MDR bacteria to humans, other animal species and environment. Urgent measures, including the establishment of mandatory monitoring for antimicrobial resistance (AMR) and the enforcement of restrictive antibiotic use policies in exotic pets, should be implemented to mitigate the risk of further spread and safeguard public and animal health.

Co-Occurrence of tet(X4) and blaNDM-5 in Escherichia coli Isolates of Inpatient Origin in Guangzhou, China.

Tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales and Acinetobacter in recent years. The emergence of antibiotic-resistant bacteria and antibiotic-resistant genes has threatened the effectiveness of antibiotics and public health with the excessive use of antibiotics in clinics. However, the emergence and dissemination of high-level mobile tigecycline-resistance gene tet(X) is challenging for clinical effectiveness of antimicrobial agent. This study aimed to characterize an E. coli strain T43, isolated from an inpatient in a teaching hospital in China. The E. coli T43 was resistant to almost all antimicrobials except colistin and consisted of a 4,774,080 bp chromosome and three plasmids. Plasmids pT43-1 and pT43-2 contained tigecycline-resistance gene tet(X4). Plasmid pT43-1 had a size of 152,423 bp with 51.05% GC content and harbored 151 putative open reading frames. pT43-1 was the largest plasmid in strain T43 and carried numerous resistance genes, especially tigecycline resistance gene tet(X4) and carbapenemase resistance gene blaNDM-5. The tet(X) gene was associated with IS26. Co-occurrence of numerous resistance genes in a single plasmid possibly contributed to the dissemination of these genes under antibiotics stress. It might explain the presence of clinically crucial resistance genes tet(X) and blaNDM-5 in clinics. This study suggested the applicable use of antibiotics and continued surveillance of tet(X) and blaNDM-5 in clinics are imperative.

Searching for Antimicrobial-Producing Bacteria from Soils through an Educational Project and Their Evaluation as Potential Biocontrol Agents.

Antimicrobial resistance (AMR) is a serious threat to public health due to the lack of effective drugs to combat infectious diseases, which generates the need to search for new antimicrobial substances. In this study, the potential of soil as a source of antimicrobial-producing bacteria (APB) was investigated and the importance of the connection between education and science was emphasized, using service-learning methodologies. Sixty-one soil samples were collected, and 1220 bacterial isolates were recovered. Eighteen of these isolates showed antimicrobial activity against at least 1 of the 12 indicator bacteria tested (including multidrug-resistant and relevant pathogens). The 18 APB were identified by MALDI-TOF and 6 different genera (Bacillus, Brevibacillus, Lysinobacillus, Peribacillus, Streptomyces, and Advenella) and 10 species were identified. The 18 APB were tested for antifungal activity against four phytopathogenic fungi (Botritis cynerea, Lecanicillium fungicola, Trichoderma harzianum, and Cladobotryum mycophilum). Moreover, the antibiotic susceptibility of APB was tested using the disk-diffusion method as well as their β-hemolytic activity (important safety criteria for potential future applications). A total of 10 of the 18 APB were able to inhibit at least 50% of indicator bacteria tested, including methicillin-resistant Staphylococcus aureus (MRSA), among others. A total of 4 of the 18 APB (3 Bacillus pumilus and 1 Bacillus altitudinis) showed inhibitory activity against two of the four fungal pathogens tested (B. cinerea and L. fungicola), as well as against 5-7 of the 12 bacterial pathogen indicators; these 4 isolates showed susceptibility to the antibiotics tested and lacked β-hemolytic activity and were considered promising APB for use as potential biocontrol agents. In addition, one Brevibacillus laterosporus strain had activity against 83% of indicator bacteria tested including Escherichia coli, MRSA and other methicillin-resistant staphylococci, as well as vancomycin-resistant enterococci (but not against fungi). These results show that soil is a source of APB with relevant antibacterial and antifungal activities, and also emphasize the importance of education and science to raise public awareness of the AMR problem and the strategies to control it.

Multidrug-resistant pathogens contaminate river water used in irrigation in disenfranchised communities

The contamination of fresh surface waters poses a significant burden on human health and prosperity, especially in marginalized communities with limited resources and inadequate infrastructure. Here, we performed in-depth genomic analyses of multidrug-resistant bacteria (MDR-B) isolated from Al-Oueik river water that is used for irrigation of agricultural fields in a disenfranchised area that also hosts a makeshift Syrian refugee camp. A composite freshwater sample was filtered. Faecal coliforms were counted and extended spectrum cephalosporins and/or ertapenem resistant bacteria were screened. Isolates were identified using MALDI-TOF-MS and analysed using whole-genome sequencing (WGS) to identify the resistome, sequence types, plasmid types, and virulence genes. Approximately 106 CFU/100 mL of faecal coliforms were detected in the water. Four drug-resistant Gram-negative bacteria were identified, namely Escherichia coli, Klebsiella pneumoniae, Enterobacter hormaechei, and Pseudomonas otitidis. Notably, the E. coli isolate harboured blaNDM-5 and a YRIN-inserted PBP3, representing an emerging public health challenge. The K. pneumoniae isolate carried blaSHV-187 as well as mutations in the gene encoding the OmpK37 porin. Enterobacter hormaechei and P. otitidis harboured blaACT-16 and blaPOM-1, respectively. This report provides comprehensive genomic analyses of MDR-B in irrigation water in Lebanon. Our results further support that irrigation water contaminated with faecal material can be a reservoir of important MDR-B, which can spread to adjacent agricultural fields and other water bodies, posing both public health and food safety issues. Therefore, there is an urgent need to implement effective water quality monitoring and management programs to control the proliferation of antibiotic-resistant pathogens in irrigation water in Lebanon.

StenM_174: A Novel Podophage That Infects a Wide Range of Stenotrophomonas spp. and Suggests a New Subfamily in the Family Autographiviridae.

Stenotrophomonas maltophilia was discovered as a soil bacterium associated with the rhizosphere. Later, S. maltophilia was found to be a multidrug-resistant hospital-associated pathogen. Lytic bacteriophages are prospective antimicrobials; therefore, there is a need for the isolation and characterization of new Stenotrophomonas phages. The phage StenM_174 was isolated from litter at a poultry farm using a clinical strain of S. maltophilia as the host. StenM_174 reproduced in a wide range of clinical and environmental strains of Stenotrophomonas, mainly S. maltophilia, and it had a podovirus morphotype. The length of the genomic sequence of StenM_174 was 42,956 bp, and it contained 52 putative genes. All genes were unidirectional, and 31 of them encoded proteins with predicted functions, while the remaining 21 were identified as hypothetical ones. Two tail spike proteins of StenM_174 were predicted using AlphaFold2 structural modeling. A comparative analysis of the genome shows that the Stenotrophomonas phage StenM_174, along with the phages Ponderosa, Pepon, Ptah, and TS-10, can be members of the new putative genus Ponderosavirus in the Autographiviridae family. In addition, the analyzed data suggest a new subfamily within this family.

Antibiotic adjuvants: synergistic tool to combat multi-drug resistant pathogens.

The rise of multi-drug resistant (MDR) pathogens poses a significant challenge to the field of infectious disease treatment. To overcome this problem, novel strategies are being explored to enhance the effectiveness of antibiotics. Antibiotic adjuvants have emerged as a promising approach to combat MDR pathogens by acting synergistically with antibiotics. This review focuses on the role of antibiotic adjuvants as a synergistic tool in the fight against MDR pathogens. Adjuvants refer to compounds or agents that enhance the activity of antibiotics, either by potentiating their effects or by targeting the mechanisms of antibiotic resistance. The utilization of antibiotic adjuvants offers several advantages. Firstly, they can restore the effectiveness of existing antibiotics against resistant strains. Adjuvants can inhibit the mechanisms that confer resistance, making the pathogens susceptible to the action of antibiotics. Secondly, adjuvants can enhance the activity of antibiotics by improving their penetration into bacterial cells, increasing their stability, or inhibiting efflux pumps that expel antibiotics from bacterial cells. Various types of antibiotic adjuvants have been investigated, including efflux pump inhibitors, resistance-modifying agents, and compounds that disrupt bacterial biofilms. These adjuvants can act synergistically with antibiotics, resulting in increased antibacterial activity and overcoming resistance mechanisms. In conclusion, antibiotic adjuvants have the potential to revolutionize the treatment of MDR pathogens. By enhancing the efficacy of antibiotics, adjuvants offer a promising strategy to combat the growing threat of antibiotic resistance. Further research and development in this field are crucial to harness the full potential of antibiotic adjuvants and bring them closer to clinical application.

Impact of antimicrobial resistance in critically ill patients in the intensive care unit

According to the Pan American Health Organization, multidrug-resistant pathogens are responsible for an increase in morbidity and mortality among hospitalized patients, leading to higher healthcare costs due to the need for prescribing more expensive medications. The aim of the research was to identify, through literature review, the impact of antimicrobial resistance in Intensive Care Units. The bibliographic review study employed a qualitative methodology; its scope was explanatory, and it utilized the historical-logical method for theoretical knowledge acquisition. For empirical knowledge, documentary analysis was used, including publications found in databases such as Scielo, PubMed, Lilacs, Dialnet, Redalyc, Google Scholar, Elsevier, institutional repositories, among others. It was evidenced that the direct causes of death and bacterial resistance in the Intensive Care Unit are sepsis, followed by septic shock, the multi-organ dysfunction syndrome, and some of the antimicrobials currently used in ICUs, such as Piperacillin-Tazobactam, Cefepime, Amikacin, Cefotaxime, and the germs that showed resistance to these antimicrobials, firstly identified were Enterobacter Aerogenes, Escherichia coli, Staphylococcus Aureus. It is concluded that, in terms of the incidence of healthcare-associated infections, there is a significant impact on the health system, increasing the morbidity and mortality of the patient by up to 50 %, including longer hospital stays, greater use of antibiotics, worse prognosis, higher complication rates, and even death

Effective Stakeholder Engagement for Collation, Analysis and Expansion of Antimicrobial Resistance (AMR) Data: A CAPTURA Experience.

An effective implementation of antimicrobial resistance (AMR) surveillance projects requires sustainable and multidisciplinary engagement with stakeholders from various backgrounds, interests and aims. The "Capturing Data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia" (CAPTURA) project, funded by the Fleming Fund, initially targeted 12 countries in South Asia (SA) and Southeast Asia (SEA) to "expand the volume of historical and current data on AMR and antimicrobial usage" and support local agencies through capacity building activities. In this article, we focus on early stakeholder engagement activities and present overall statistics on AMR data collated from 72 laboratories across seven countries. This included 2.3 million records of antimicrobial susceptibility testing (AST) data, which were curated, analyzed, and shared back to the facilities for informed decision making. Approximately 98% of the data collated by CAPTURA originated from laboratories based in SA countries. Furthermore, country-wide data were analyzed to identify commonly reported pathogens in each country, followed by descriptions of AST practices and multidrug-resistant (MDR) pathogens. Overall, we found meager adherence to standard guidelines to perform and record AST results, and a significant number of MDR pathogens were reported. We conclude that close collaboration with the existing national mechanisms for identifying AMR data sources was crucial for the project's success. Although we show a vast retrospective dataset on AMR is available for data sharing in Asia, there remain critical gaps in data generation/management practice and analysis capacity for AMR data at most facilities.

Exploring Roles of the Polysaccharide Capsule in Pathogenesis of Hypervirulent Acinetobacter baumannii Clinical Isolate Lac-4.

The frequently multidrug-resistant bacterial pathogen Acinetobacter baumannii is a leading cause of nosocomial infections, including ventilator-associated pneumonia, such that the World Health Organization and US Centers for Disease Control and Prevention have declared it a top priority candidate for novel drug development. Nearly all clinical A. baumannii strains express a thick surface polysaccharide capsule that protects against desiccation, host defenses, and disinfectants. In this study, we investigated the contribution of the polysaccharide capsule to virulence caused by the A. baumannii clinical isolate Ab Lac-4, which is rare in its ability to cause pneumonia and disseminated sepsis in healthy mice. We assessed the role of the capsule in wildtype Lac-4 (WT) by generating a premature stop codon in wza, which codes for the polysaccharide export protein. The wza# mutant was hypersensitive to killing by complement, whole blood, and healthy human neutrophils compared to WT and a revertant mutant (wza-Rev). Furthermore, the wza# mutant was highly attenuated in murine sepsis and unable to disseminate from the lungs during pneumonia. This study reinforces the capsule as a key contributor to Ab Lac-4 hypervirulence.

Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria.

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain on four major pathogens, i.e., carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant E. faecium (VRE) strains. We screened the effect of these derivatives on biofilm formation and eradication. Derivatives 4e (for CRAB, VRE, and MRSA) and 4f (for all the strains) were the most potent ones and displayed activities as good as those of conventional antibiotics. We also identified 11 compounds able to decrease by more than 40% the production of pyocyanin, a major virulence factor of P. aeruginosa. We demonstrated that 4f treatment acts against bacterial infections in Galleria mellonella and significantly prolonged larvae survival (from 50% to 80%) after 24 h of CRAB, VRE, and MRSA infections. As shown by proteomic studies, 4f triggered distinct cellular responses depending on the bacterial species but essentially linked to cell envelope. Its interesting antibiofilm and antivirulence properties make it a promising a candidate for use in therapeutics.

Impact of financial incentives for infection prevention and management on antibiotic use: A Korea National Health Insurance cohort study

BackgroundThe Korean government implemented financial incentives to enhance infection prevention and management within general hospital settings. This study aimed to evaluate the impact of infection control compensation on antibiotic usage using a controlled interrupted time series analysis. MethodsThe main unit of analysis was 270,901 inpatient episodes extracted from the Korean National Health Insurance Service Cohort Database from 2013 to 2019. The 96-month period was examined before and after the intervention, which was set to September 1, 2017, by applying a 1-year lag time after the incentive was introduced. Segmented regression was used to estimate the effects of interventions in a controlled interrupted time series. Hospitals that received nationwide financial incentives for infection prevention and management were included in the analysis. The study’s primary outcome was the use of antibiotics based on the WHO Access, Watch, and Reserve (AWaRe) classification of antibiotics, and the secondary outcome was the number of days of antibiotic use as days of therapy (DOTs) per patient day (PD). ResultsThe probability of overall antibiotic use decreased between incentivized and unincentivized hospitals (odds ratio [OR], 0.922; 95% confidence interval [CI], 0.859–1.000). The difference in level change in the use of third-generation cephalosporins (OR,0.894; 95% CI, 0.817–0.977) and carbapenem (OR,0.790; 95% CI, 0.630–0.992) was significantly reduced between incentivized and unincentivized hospitals. The difference in slope change on DOTs/PD of glycopeptides was − 0.005 DOT/PDs, and that of carbapenem was − 0.003 between incentivized and unincentivized hospitals. ConclusionWe observed that incentives for infection prevention and management have had a positive impact on some aspects of antibiotic usage. A partial decrease was observed in antibiotic use, accompanied by a modest reduction in DOTs/PD, particularly for antibiotics aimed at addressing multidrug-resistant pathogens. Further investigation is necessary to establish evidence for extending these incentives.

Cephalosporin resistance, tolerance, and approaches to improve their activities.

Cephalosporins comprise a β-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.