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Euro Surveillance : Bulletin Europeen... Jun 2024In 2022, an outbreak with severe bloodstream infections caused by occurred in an adult intensive care unit (ICU) in Hungary. Eight cases, five of whom died, were...
In 2022, an outbreak with severe bloodstream infections caused by occurred in an adult intensive care unit (ICU) in Hungary. Eight cases, five of whom died, were detected. Initial control measures could not stop the outbreak. We conducted a matched case-control study. In univariable analysis, the cases were more likely to be located around one sink in the ICU and had more medical procedures and medications than the controls, however, the multivariable analysis was not conclusive. Isolates from blood cultures of the cases and the ICU environment were closely related by whole genome sequencing and resistant or tolerant against the quaternary ammonium compound surface disinfectant used in the ICU. Thus, was able to survive in the environment despite regular cleaning and disinfection. The hospital replaced the disinfectant with another one, tightened the cleaning protocol and strengthened hand hygiene compliance among the healthcare workers. Together, these control measures have proved effective to prevent new cases. Our results highlight the importance of multidisciplinary outbreak investigations, including environmental sampling, molecular typing and testing for disinfectant resistance.
Topics: Humans; Serratia marcescens; Disease Outbreaks; Cross Infection; Hungary; Intensive Care Units; Serratia Infections; Disinfectants; Case-Control Studies; Male; Female; Adult; Middle Aged; Whole Genome Sequencing; Disinfection; Aged; Infection Control; Drug Resistance, Bacterial
PubMed: 38940004
DOI: 10.2807/1560-7917.ES.2024.29.26.2300492 -
Frontiers in Microbiology 2024This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics...
This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics as a therapeutic strategy for CRC patients with AIEC infections. Considering the pivotal role of integrons in bacterial antibiotic resistance, the frequency of class 1 and 2 integrons in AIEC isolated from CRC patients, in one of the referenced 3 gastroenterology clinics in Isfahan, Iran was examined. AIEC strains were isolated from the colorectal biopsies and their antimicrobial sensitivity was assessed using the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect and . The multilocus sequence typing (MLST) method was utilized to type 10 selected isolates. Of the 150 samples, 24 were identified as AIEC, with the highest number isolated from CRC2 (33.4%) and CRC1 (29.16%), and the least from the FH group (8.3%) and control group (12.5%). in 79.2% and in 45.8% of AIEC strains were found and 41.6% of strains had both integrons. AIEC isolates with int1 exhibited the highest sensitivity to trimethoprim-sulfamethoxazole (57.9%), while those with int2 showed the highest sensitivity to ciprofloxacin (63.6%). A significant association between resistance to rifampin and integron 2 presence in AIEC isolates was observed. Furthermore, a significant correlation between integron 1 presence, invasion, survival, and replication within macrophages in AIEC strains was identified. MLST analysis revealed ST131 from CC131 with integron 1 as the most common sequence type (ST). The emergence of such strains in CRC populations poses a serious public health threat. The distribution pattern of STs varied among studied groups, with pandemic STs highlighting the importance of examining and treating patients infected with these isolates. Comprehensive prospective clinical investigations are warranted to assess the prognostic value of detecting this pathovar in CRC and to evaluate therapeutic techniques targeting drug-resistant AIECs, such as phage therapy, bacteriocins, and anti-adhesion compounds, for CRC prevention and treatment.
PubMed: 38939191
DOI: 10.3389/fmicb.2024.1366719 -
Chemical Science Jun 2024Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There...
Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There is therefore an urgent need for new molecules that function through novel mechanisms of action to combat AMR. The bacterial DNA-repair and SOS-response pathways promote survival of pathogens in infection settings and also activate hypermutation and resistance mechanisms, making these pathways attractive targets for new therapeutics. Small molecules, such as IMP-1700, potentiate DNA damage and inhibit the SOS response in methicillin-resistant ; however, understanding of the structure-activity relationship (SAR) of this series is lacking. We report here the first comprehensive SAR study of the IMP-1700 scaffold, identifying key pharmacophoric groups and delivering the most potent analogue reported to date, OXF-077. Furthermore, we demonstrate that as a potent inhibitor of the mutagenic SOS response, OXF-077 suppresses the rate of ciprofloxacin resistance emergence in . This work supports SOS-response inhibitors as a novel means to combat AMR, and delivers OXF-077 as a tool molecule for future development.
PubMed: 38939155
DOI: 10.1039/d4sc00995a -
Biomaterials Research 2024The management of infected wounds poses a significant challenge due to the growing issue of antibiotic resistance, underscoring the urgent necessity to innovate and...
The management of infected wounds poses a significant challenge due to the growing issue of antibiotic resistance, underscoring the urgent necessity to innovate and implement alternative therapeutic strategies. These strategies should be capable of eliminating bacterial infections in infected wounds while circumventing the induction of multi-drug resistance. In the current study, we developed an easily prepared and injectable fibrin gel (FG) loaded with nanoparticles (NPs) that exhibit antibacterial and immunomodulatory properties to facilitate the healing of infected wounds. Initially, a novel type of NP was generated through the electrostatic interaction between the photothermal agent, mPEG-modified polydopamine (MPDA), and the nitric oxide (NO) donor, S-nitrosocysteamine (SNO). This interaction resulted in the formation of NPs referred to as SNO-loaded MPDA (SMPDA). Subsequently, the SMPDA was encapsulated into the FG using a double-barreled syringe, thereby producing the SMPDA-loaded FG (SMPDA/G). Experimental results revealed that SMPDA/G could effectively eliminate bacterial infections and alter the immune microenvironment. This efficacy is attributed to the synergistic combination of NO therapy and photothermal therapy, along with the role of SMPDA in facilitating M2 macrophage polarization within the gel. Accordingly, these findings suggest that the SMPDA/G holds substantial promise for clinical application in infected wound healing.
PubMed: 38938648
DOI: 10.34133/bmr.0019 -
Health Technology Assessment... Jun 2024To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund...
BACKGROUND
To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
METHODS
The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
RESULTS
Among isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
CONCLUSION
This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
LIMITATIONS
Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
FUTURE WORK
Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
STUDY REGISTRATION
No registration of this study was undertaken.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in ; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Cephalosporins; Anti-Bacterial Agents; Quality-Adjusted Life Years; Cost-Benefit Analysis; England; Technology Assessment, Biomedical; Cefiderocol; Gram-Negative Bacterial Infections; State Medicine; Quality of Life
PubMed: 38938145
DOI: 10.3310/YGWR4511 -
Animal Bioscience Jun 2024This research aimed to analyze the prevalence, molecular characteristics, toxinotyping, alpha toxin production potential, and antibiotic resistance pattern of...
OBJECTIVE
This research aimed to analyze the prevalence, molecular characteristics, toxinotyping, alpha toxin production potential, and antibiotic resistance pattern of Clostridium perfringens (C. perfringens) isolates in meat samples collected from various sources.
METHODS
Sixty meat samples were screened for alpha toxin using Enzyme-Linked Immunosorbent Assay (ELISA), revealing a positivity rate of 13.3%, predominantly in raw poultry meat. Subsequent culturing on Perfringens agar identified nine samples harboring characteristic C. perfringens colonies, primarily isolated from raw poultry meat. Molecular confirmation through 16S rRNA gene amplification and sequencing authenticated twelve isolates as C. perfringens, with nine strains exhibiting genetic resemblance to locally isolated strains. Toxinotyping assays targeting alpha toxin-specific genes confirmed all nine isolates as type A C. perfringens, with no detection of beta or epsilon toxin genes. Hemolytic assays demonstrated varying alpha toxin production potentials among isolates, with accession number OQ721004.1 displaying the highest production capacity. Moreover, antibiotic resistance profiling revealed multi-drug resistance patterns among the isolates.
RESULTS
The study identified distinct clusters within C. perfringens strains, indicating variations. Phylogenetic analysis delineated genetic relatedness among strains, elucidating potential evolutionary paths and divergences.
CONCLUSION
The findings underscore the need for robust surveillance and control measures to mitigate the risk of C. perfringens contamination in meat products, particularly in raw poultry meat. Enhanced monitoring and prudent antimicrobial stewardship practices are warranted in both veterinary and clinical settings to address the observed antibiotic resistance profiles and prevent foodborne outbreaks.
PubMed: 38938034
DOI: 10.5713/ab.24.0210 -
Human Genomics Jun 2024Wastewater surveillance (WWS) acts as a vigilant sentinel system for communities, analysing sewage to protect public health by detecting outbreaks and monitoring trends...
EU surveys insights: analytical tools, future directions, and the essential requirement for reference materials in wastewater monitoring of SARS-CoV-2, antimicrobial resistance and beyond.
BACKGROUND
Wastewater surveillance (WWS) acts as a vigilant sentinel system for communities, analysing sewage to protect public health by detecting outbreaks and monitoring trends in pathogens and contaminants. To achieve a thorough comprehension of present and upcoming practices and to identify challenges and opportunities for standardisation and improvement in WWS methodologies, two EU surveys were conducted targeting over 750 WWS laboratories across Europe and other regions. The first survey explored a diverse range of activities currently undertaken or planned by laboratories. The second survey specifically targeted methods and quality controls utilised for SARS-CoV-2 surveillance.
RESULTS
The findings of the two surveys provide a comprehensive insight into the procedures and methodologies applied in WWS. In Europe, WWS primarily focuses on SARS-CoV-2 with 99% of the survey participants dedicated to this virus. However, the responses highlighted a lack of standardisation in the methodologies employed for monitoring SARS-CoV-2. The surveillance of other pathogens, including antimicrobial resistance, is currently fragmented and conducted by only a limited number of laboratories. Notably, these activities are anticipated to expand in the future. Survey replies emphasise the collective recognition of the need to enhance the accuracy of results in WWS practices, reflecting a shared commitment to advancing precision and effectiveness in WWS methodologies.
CONCLUSIONS
These surveys identified a lack of standardised common procedures in WWS practices and the need for quality standards and reference materials to enhance the accuracy and reliability of WWS methods in the future. In addition, it is important to broaden surveillance efforts beyond SARS-CoV-2 to include other emerging pathogens and antimicrobial resistance to ensure a comprehensive approach to protecting public health.
Topics: Humans; Wastewater; SARS-CoV-2; COVID-19; Europe; Surveys and Questionnaires; Sewage; Drug Resistance, Microbial
PubMed: 38937848
DOI: 10.1186/s40246-024-00641-5 -
Integrated surveillance systems for antibiotic resistance in a One Health context: a scoping review.BMC Public Health Jun 2024Antibiotic resistance (ABR) has emerged as a major threat to health. Properly informed decisions to mitigate this threat require surveillance systems that integrate... (Review)
Review
BACKGROUND
Antibiotic resistance (ABR) has emerged as a major threat to health. Properly informed decisions to mitigate this threat require surveillance systems that integrate information on resistant bacteria and antibiotic use in humans, animals, and the environment, in line with the One Health concept. Despite a strong call for the implementation of such integrated surveillance systems, we still lack a comprehensive overview of existing organizational models for integrated surveillance of ABR. To address this gap, we conducted a scoping review to characterize existing integrated surveillance systems for ABR.
METHODS
The literature review was conducted using the PRISMA guidelines. The selected integrated surveillance systems were assessed according to 39 variables related to their organization and functioning, the socio-economic and political characteristics of their implementation context, and the levels of integration reached, together with their related outcomes. We conducted two distinct, complementary analyses on the data extracted: a descriptive analysis to summarize the characteristics of the integrated surveillance systems, and a multiple-correspondence analysis (MCA) followed by a hierarchical cluster analysis (HCA) to identify potential typology for surveillance systems.
RESULTS
The literature search identified a total of 1330 records. After the screening phase, 59 references were kept from which 14 integrated surveillance systems were identified. They all operate in high-income countries and vary in terms of integration, both at informational and structural levels. The different systems combine information from a wide range of populations and commodities -in the human, animal and environmental domains, collection points, drug-bacterium pairs, and rely on various diagnostic and surveillance strategies. A variable level of collaboration was found for the governance and/or operation of the surveillance activities. The outcomes of integration are poorly described and evidenced. The 14 surveillance systems can be grouped into four distinct clusters, characterized by integration level in the two dimensions. The level of resources and regulatory framework in place appeared to play a major role in the establishment and organization of integrated surveillance.
CONCLUSIONS
This study suggests that operationalization of integrated surveillance for ABR is still not well established at a global scale, especially in low and middle-income countries and that the surveillance scope is not broad enough to obtain a comprehensive understanding of the complex dynamics of ABR to appropriately inform mitigation measures. Further studies are needed to better characterize the various integration models for surveillance with regard to their implementation context and evaluate the outcome of these models.
Topics: Humans; One Health; Drug Resistance, Microbial; Anti-Bacterial Agents; Population Surveillance
PubMed: 38937706
DOI: 10.1186/s12889-024-19158-6 -
BMC Microbiology Jun 2024Bacterial antimicrobial resistance poses a severe threat to humanity, necessitating the urgent development of new antibiotics. Recent advances in genome sequencing offer...
BACKGROUND
Bacterial antimicrobial resistance poses a severe threat to humanity, necessitating the urgent development of new antibiotics. Recent advances in genome sequencing offer new avenues for antibiotic discovery. Paenibacillus genomes encompass a considerable array of antibiotic biosynthetic gene clusters (BGCs), rendering these species as good candidates for genome-driven novel antibiotic exploration. Nevertheless, BGCs within Paenibacillus genomes have not been extensively studied.
RESULTS
We conducted an analysis of 554 Paenibacillus genome sequences, sourced from the National Center for Biotechnology Information database, with a focused investigation involving 89 of these genomes via antiSMASH. Our analysis unearthed a total of 848 BGCs, of which 716 (84.4%) were classified as unknown. From the initial pool of 554 Paenibacillus strains, we selected 26 available in culture collections for an in-depth evaluation. Genomic scrutiny of these selected strains unveiled 255 BGCs, encoding non-ribosomal peptide synthetases, polyketide synthases, and bacteriocins, with 221 (86.7%) classified as unknown. Among these strains, 20 exhibited antimicrobial activity against the gram-positive bacterium Micrococcus luteus, yet only six strains displayed activity against the gram-negative bacterium Escherichia coli. We proceeded to focus on Paenibacillus brasilensis, which featured five new BGCs for further investigation. To facilitate detailed characterization, we constructed a mutant in which a single BGC encoding a novel antibiotic was activated while simultaneously inactivating multiple BGCs using a cytosine base editor (CBE). The novel antibiotic was found to be localized to the cell wall and demonstrated activity against both gram-positive bacteria and fungi. The chemical structure of the new antibiotic was elucidated on the basis of ESIMS, 1D and 2D NMR spectroscopic data. The novel compound, with a molecular weight of 926, was named bracidin.
CONCLUSIONS
This study outcome highlights the potential of Paenibacillus species as valuable sources for novel antibiotics. In addition, CBE-mediated dereplication of antibiotics proved to be a rapid and efficient method for characterizing novel antibiotics from Paenibacillus species, suggesting that it will greatly accelerate the genome-based development of new antibiotics.
Topics: Paenibacillus; Anti-Bacterial Agents; Multigene Family; Genome, Bacterial; Peptide Synthases; Polyketide Synthases; Bacteriocins; Biosynthetic Pathways; Bacterial Proteins; Drug Discovery
PubMed: 38937695
DOI: 10.1186/s12866-024-03375-5 -
Scientific Reports Jun 2024Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus...
Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus aureus and Staphylococci other than S. aureus (SOSA) among young volunteers in Egypt to determine their risk potential. Nasal swabs collected over 1 week in June 2019 from 196 volunteers were cultured for staphylococcus isolation. The participants were interviewed to assess sex, age, general health, hospitalization and personal hygiene habits. Identification was carried out using biochemical tests and VITEK 2 automated system. Disc diffusion and minimum inhibitory concentration tests were performed to determine antibiotic susceptibility. Screening for macrolide resistance genes (ermA, ermB, ermC, ermT and msrA) was performed using polymerase chain reaction. Thirty four S. aureus and 69 SOSA were obtained. Multi-drug resistance (MDR) was detected among most staphylococcal species, ranging from 30.77% among S. hominis to 50% among S. epidermidis. Phenotypic resistance to all tested antibiotics, except for linezolid, was observed. Susceptibility to rifampicin, vancomycin and teicoplanin was highest. ermB showed the highest prevalence among all species (79.41% and 94.2% among S. aureus and SOSA, respectively), and constitutive macrolide-lincosamide-streptogramin B (MLS) resistance was equally observed in S. aureus and SOSA (11.11% and 16.22%, respectively), whereas inducible MLS resistance was more often found in S. aureus (77.78% and 43.24%, respectively). The species or resistance level of the carried isolates were not significantly associated with previous hospitalization or underlying diseases. Although over all colonization and carriage of resistance genes are within normal ranges, the increased carriage of MDR S. aureus is alarming. Also, the fact that many macrolide resitance genes were detected should be a warning sign, particularly in case of MLS inducible phenotype. More in depth analysis using whole genome sequencing would give a better insight into the MDR staphylococci in the community in Egypt.
Topics: Humans; Egypt; Female; Male; Staphylococcus; Microbial Sensitivity Tests; Staphylococcal Infections; Anti-Bacterial Agents; Adult; Phenotype; Young Adult; Genotype; Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Adolescent
PubMed: 38937465
DOI: 10.1038/s41598-024-60924-8