ABSTRACT
Phage therapy is gaining increasing interest in the fight against critically antibiotic-resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here, we combine large-scale phylogeographic analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter baumannii, a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within 6 years. As we demonstrate in Eastern Europe, this spatiotemporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of phage cocktails against prevalent strain types using in vitro and animal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy.
Subject(s)
Acinetobacter baumannii , Bacteriophages , Phage Therapy , Phage Therapy/methods , Acinetobacter baumannii/virology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Animals , Humans , Bacteriophages/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Acinetobacter Infections/therapy , Acinetobacter Infections/microbiology , Genomics/methods , Drug Resistance, Bacterial/genetics , Mice , Phylogeography , Carbapenems/pharmacology , Carbapenems/therapeutic useABSTRACT
BACKGROUND: This phase 2 extension explored the long-term antibody persistence of an investigational Clostridioides difficile vaccine and the safety, tolerability, and immunogenicity of dose 4 approximately 12 months post-dose 3. METHODS: One year post-dose 3, healthy US 65- to 85-year-olds (N = 300) were randomized to dose 4 of vaccine at previously received antigen levels (100 or 200 µg) or placebo. Assessments included safety and percentages of participants achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively). RESULTS: In participants previously given three 200-µg doses and placebo in the extension, toxin A and B neutralizing antibodies were above prevaccination levels 48 months post-dose 3 (36 months after placebo); 24.0% and 26.0% had toxin A and B antibodies at or above prespecified thresholds, respectively. Neutralizing antibodies increased post-dose 4 (12 months post-dose 3) and persisted to 36 months post-dose 4. Thirty days post-dose 4, all participants had toxin A and 86.5% to 100% had toxin B titers at or above prespecified thresholds. Local reactions were more frequent in vaccine recipients. Systemic and adverse event frequencies were similar across groups. CONCLUSIONS: C difficile vaccine immune responses persisted 48 months post-dose 3. Dose 4 was immunogenic and well tolerated, supporting continued development. Clinical Trials Registration. ClinicalTrials.gov NCT02561195.
Subject(s)
Clostridioides difficile , Adult , Humans , Bacterial Vaccines , Antibodies, Neutralizing , Antibodies, Bacterial , Antibody Formation , Immunogenicity, Vaccine , Antibodies, Viral , Double-Blind MethodABSTRACT
Many hospitals have stopped or are considering stopping universal admission testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss reasons why admission testing should still be part of a layered system to prevent hospital-acquired SARS-CoV-2 infections during times of significant community transmission. These include the morbidity of SARS-CoV-2 in vulnerable patients, the predominant contribution of presymptomatic and asymptomatic people to transmission, the high rate of transmission between patients in shared rooms, and data suggesting surveillance testing is associated with fewer nosocomial infections. Preferences of diverse patient populations, particularly the hardest-hit communities, should be surveyed and used to inform prevention measures. Hospitals' ethical responsibility to protect patients from serious infections should predominate over concerns about costs, labor, and inconvenience. We call for more rigorous data on the incidence and morbidity of nosocomial SARS-CoV-2 infections and more research to help determine when to start, stop, and restart universal admission testing and other prevention measures.
Subject(s)
COVID-19 , Cross Infection , Humans , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Cross Infection/epidemiology , Cross Infection/prevention & control , HospitalizationABSTRACT
Over the past 10 years, there has been a rapid expansion in the use of extracorporeal membrane oxygenation (ECMO) in the care of patients with refractory cardiac or respiratory failure. Infectious diseases clinicians must reconcile conflicting evidence from limited studies as they develop practices at their own institutions, which has resulted in considerably different practices globally. This review describes infection control and prevention as well as antimicrobial prophylaxis strategies in this population. Data on diagnostics and treatment for patients receiving ECMO with a focus on diagnostic and antimicrobial stewardship is then examined. This review summarizes gaps in the current ECMO literature and proposes future needs, including developing clear definitions for infections and encouraging transparent reporting of practices at individual facilities in future clinical trials.
Subject(s)
Cross Infection , Extracorporeal Membrane Oxygenation , Infection Control , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Cross Infection/prevention & control , Infection Control/methods , Antimicrobial Stewardship , Adult , Antibiotic Prophylaxis , Communicable DiseasesABSTRACT
In 2021, we identified a cluster of Elizabethkingia miricola cases in an intensive care unit in Spain. Because E. miricola is not considered a special surveillance agent in Spain, whole-genome sequencing was not performed. The bacterial source was not identified. All Elizabethkingia species should be listed as special surveillance bacteria.
Subject(s)
Flavobacteriaceae , Intensive Care Units , Opportunistic Infections , Humans , Spain/epidemiology , Whole Genome SequencingABSTRACT
Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020-2022, an outbreak of 21 invasive Serratia infections occurred in a prison in California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons.
Subject(s)
Cross Infection , Disinfectants , Prisoners , Serratia Infections , Humans , Serratia marcescens/genetics , Serratia Infections/epidemiology , Prisons , Cross Infection/microbiology , Disease Outbreaks , California/epidemiologyABSTRACT
Pseudomonas aeruginosa (PA) is an important opportunistic pathogen that causes different infections on immunocompromised patients. Within PA accessory genome, differences in virulence, antibiotic resistance and biofilm formation have been described between strains, leading to the emergence of multidrug-resistant strains. The genome sequences of 17 strains isolated from patients with healthcare-associated infections in a Mexican hospital were genomically and phylogenetically analyzed and antibiotic resistance genes, virulence genes, and biofilm formation genes were detected. Fifteen of the 17 strains were resistant to at least two of the carbapenems meropenem, imipenem, and the monobactam aztreonam. The antibiotic resistance (mexA, mexB, and oprM) and the biofilm formation (pslA and pslD) genes were detected in all strains. Differences were found between strains in accessory genome size. The strains had different sequence types, and seven strains had sequence types associated with global high risk epidemic PA clones. All strains were represented in two groups among PA global strains. In the 17 strains, horizontally acquired resistance genes to aminoglycosides and beta-lactams were found, mainly, and between 230 and 240 genes that encode virulence factors. The strains under study were variable in terms of their accessory genome, antibiotic resistance, and virulence genes. With these characteristics, we provide information about the genomic diversity of clinically relevant PA strains.
Subject(s)
Carbapenems , Pseudomonas Infections , Humans , Aztreonam , Pseudomonas aeruginosa/genetics , Anti-Bacterial Agents , Hospitals , Genomics , Delivery of Health Care , Microbial Sensitivity TestsABSTRACT
BACKGROUND: Infective endocarditis (IE) following cardiac valve surgery is associated with high morbidity and mortality. Data on the impact of iatrogenic healthcare exposures on this risk are sparse. This study aimed to investigate risk factors including healthcare exposures for post open-heart cardiac valve surgery endocarditis (PVE). METHODS: In this population-linkage cohort study, 23,720 patients who had their first cardiac valve surgery between 2001 and 2017 were identified from an Australian state-wide hospital-admission database and followed-up to 31 December 2018. Risk factors for PVE were identified from multivariable Cox regression analysis and verified using a case-crossover design sensitivity analysis. RESULTS: In 23,720 study participants (median age 73, 63% male), the cumulative incidence of PVE 15 years after cardiac valve surgery was 7.8% (95% CI 7.3-8.3%). Thirty-seven percent of PVE was healthcare-associated, which included red cell transfusions (16% of healthcare exposures) and coronary angiograms (7%). The risk of PVE was elevated for 90 days after red cell transfusion (HR = 3.4, 95% CI 2.1-5.4), coronary angiogram (HR = 4.0, 95% CI 2.3-7.0), and healthcare exposures in general (HR = 4.0, 95% CI 3.3-4.8) (all p < 0.001). Sensitivity analysis confirmed red cell transfusion (odds ratio [OR] = 3.9, 95% CI 1.8-8.1) and coronary angiogram (OR = 2.6, 95% CI 1.5-4.6) (both p < 0.001) were associated with PVE. Six-month mortality after PVE was 24% and was higher for healthcare-associated PVE than for non-healthcare-associated PVE (HR = 1.3, 95% CI 1.1-1.5, p = 0.002). CONCLUSIONS: The risk of PVE is significantly higher for 90 days after healthcare exposures and associated with high mortality.
Subject(s)
Endocarditis , Heart Valve Prosthesis , Prosthesis-Related Infections , Humans , Male , Aged , Female , Cohort Studies , Heart Valve Prosthesis/adverse effects , Australia/epidemiology , Heart Valves , Endocarditis/epidemiology , Endocarditis/etiology , Prosthesis-Related Infections/surgeryABSTRACT
The environmental bacterium Klebsiella oxytoca displays an alarming increase of antibiotic-resistant strains that frequently cause outbreaks in intensive care units. Due to its prevalence in the environment and opportunistic presence in humans, molecular surveillance (including resistance marker screening) and high-resolution cluster analysis are of high relevance. Furthermore, K. oxytoca previously described in studies is rather a species complex (KoSC) than a single species comprising at least six closely related species that are not easily differentiated by standard typing methods. To reach a discriminatory power high enough to identify and resolve clusters within these species, whole genome sequencing is necessary. The resolution is achievable with core genome multilocus sequence typing (cgMLST) extending typing of a few housekeeping genes to thousands of core genome genes. CgMLST is highly standardized and provides a nomenclature enabling cross laboratory reproducibility and data exchange for routine diagnostics. Here, we established a cgMLST scheme not only capable of resolving the KoSC species but also producing reliable and consistent results for published outbreaks. Our cgMLST scheme consists of 2,536 core genome and 2,693 accessory genome targets, with a percentage of good cgMLST targets of 98.31% in 880 KoSC genomes downloaded from the National Center for Biotechnology Information (NCBI). We also validated resistance markers against known resistance gene patterns and successfully linked genetic results to phenotypically confirmed toxic strains carrying the til gene cluster. In conclusion, our novel cgMLST enables highly reproducible typing of four different clinically relevant species of the KoSC and thus facilitates molecular surveillance and cluster investigations.
Subject(s)
Genome, Bacterial , Klebsiella oxytoca , Multilocus Sequence Typing , Multilocus Sequence Typing/methods , Klebsiella oxytoca/genetics , Klebsiella oxytoca/classification , Klebsiella oxytoca/isolation & purification , Humans , Genome, Bacterial/genetics , Phylogeny , Klebsiella Infections/microbiology , Whole Genome Sequencing , Bacterial Typing Techniques/methods , Genes, Essential/genetics , Reproducibility of ResultsABSTRACT
The reliability of Fourier-transform infrared (FT-IR) spectroscopy for Klebsiella pneumoniae typing and outbreak control has been previously assessed, but issues remain in standardization and reproducibility. We developed and validated a reproducible FT-IR with attenuated total reflectance (ATR) workflow for the identification of K. pneumoniae lineages. We used 293 isolates representing multidrug-resistant K. pneumoniae lineages causing outbreaks worldwide (2002-2021) to train a random forest classification (RF) model based on capsular (KL)-type discrimination. This model was validated with 280 contemporaneous isolates (2021-2022), using wzi sequencing and whole-genome sequencing as references. Repeatability and reproducibility were tested in different culture media and instruments throughout time. Our RF model allowed the classification of 33 capsular (KL)-types and up to 36 clinically relevant K. pneumoniae lineages based on the discrimination of specific KL- and O-type combinations. We obtained high rates of accuracy (89%), sensitivity (88%), and specificity (92%), including from cultures obtained directly from the clinical sample, allowing to obtain typing information the same day bacteria are identified. The workflow was reproducible in different instruments throughout time (>98% correct predictions). Direct colony application, spectral acquisition, and automated KL prediction through Clover MS Data analysis software allow a short time-to-result (5 min/isolate). We demonstrated that FT-IR ATR spectroscopy provides meaningful, reproducible, and accurate information at a very early stage (as soon as bacterial identification) to support infection control and public health surveillance. The high robustness together with automated and flexible workflows for data analysis provide opportunities to consolidate real-time applications at a global level. IMPORTANCE We created and validated an automated and simple workflow for the identification of clinically relevant Klebsiella pneumoniae lineages by FT-IR spectroscopy and machine-learning, a method that can be extremely useful to provide quick and reliable typing information to support real-time decisions of outbreak management and infection control. This method and workflow is of interest to support clinical microbiology diagnostics and to aid public health surveillance.
Subject(s)
Bacteria , Klebsiella pneumoniae , Humans , Klebsiella pneumoniae/genetics , Reproducibility of Results , Spectroscopy, Fourier Transform Infrared/methods , Whole Genome Sequencing , Ataxia Telangiectasia Mutated ProteinsABSTRACT
PURPOSE: Data from the intensive care component of the German hospital infection surveillance system (KISS) was used to investigate the epidemiology of pathogens responsible for the most frequent device-associated infections and their development over time. METHOD: The 10 most common pathogens were identified for ventilator-associated lower respiratory tract infections (VALRTI), catheter associated urinary tract infections (CAUTI), and central venous catheter associated bloodstream infections (CVC-BSI). The development over time was analyzed based on three five-year time periods: 2008-2012, 2013-2017, 2018-2022. RESULTS: Data from 1425 ICUs were included together with 121,762 device-associated infections with 138,299 isolated pathogens. A remarkable and significant increase in the frequency of Klebsiella spp. was found for VALRTI, that was almost twice as high during 2018-2022 compared to 2008-2012. For CAUTI, there was a significant increase of all Enterobacterales with the most prominent increase in Klebsiella spp. With regard to CVC-BSI, the situation for coagulase-negative staphylococci and E. coli was relatively stable; while there was a significant increase in Enterococcus spp. and Klebsiella spp. and a decrease in S. aureus. CONCLUSION: Knowledge about the current frequency of pathogens responsible for nosocomial infections in intensive care units is important for guiding empirical antimicrobial therapy. Data from national nosocomial infection surveillance systems can provide relevant information about the development of pathogens.
Subject(s)
Catheter-Related Infections , Cross Infection , Respiratory Tract Infections , Urinary Tract Infections , Humans , Cross Infection/epidemiology , Escherichia coli , Staphylococcus aureus , Hospitals , Urinary Tract Infections/epidemiology , Critical Care , Catheter-Related Infections/epidemiology , Catheter-Related Infections/complicationsABSTRACT
BACKGROUND: SARS-CoV-2 genomic analysis has been key to the provision of valuable data to meet both epidemiological and clinical demands. High-throughput sequencing, generally Illumina-based, has been necessary to ensure the widest coverage in global variant tracking. However, a speedier response is needed for nosocomial outbreak analyses and rapid identification of patients infected by emerging VOCs. An alternative based on nanopore sequencing may be better suited to delivering a faster response when required; however, although there are several studies offering side-by-side comparisons of Illumina and nanopore sequencing, evaluations of the usefulness in the hospital routine of the faster availability of data provided by nanopore are still lacking. RESULTS: We performed a prospective 10-week nanopore-based sequencing in MinION in a routine laboratory setting, including 83 specimens where a faster response time was necessary. The specimens analyzed corresponded to i) international travellers in which lineages were assigned to determine the proper management/special isolation of the patients; ii) nosocomial infections and health-care-worker infections, where SNP-based comparisons were required to rule in/out epidemiological relationships and tailor specific interventions iii) sentinel cases and breakthrough infections to timely report to the Public Health authorities. MinION-based sequencing was compared with the standard procedures, supported on Illumina sequencing; MinION accelerated the delivery of results (anticipating results 1-12 days) and reduced costs per sample by 28 compared to Illumina, without reducing accuracy in SNP calling. CONCLUSIONS: Parallel integration of Illumina and nanopore sequencing strategies is a suitable solution to ensure both high-throughput and rapid response to cope with accelerating the surveillance demands of SARS-CoV-2 while also maintaining accuracy.
Subject(s)
COVID-19 , Nanopore Sequencing , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Nanopore Sequencing/methods , Prospective Studies , Genomics/methodsABSTRACT
Clostridioides difficile represents a major burden to public health. As a well-known nosocomial pathogen whose occurrence is highly associated with antibiotic treatment, most examined C. difficile strains originated from clinical specimen and were isolated under selective conditions employing antibiotics. This suggests a significant bias among analyzed C. difficile strains, which impedes a holistic view on this pathogen. In order to support extensive isolation of C. difficile strains from environmental samples, we designed a detection PCR that targets the hpdBCA-operon and thereby identifies low abundances of C. difficile in environmental samples. This operon encodes the 4-hydroxyphenylacetate decarboxylase, which catalyzes the production of the antimicrobial compound para-cresol. Amplicon-based analyses of diverse environmental samples demonstrated that the designed PCR is highly specific for C. difficile and successfully detected C. difficile despite its absence in general 16S rRNA gene-based detection strategies. Further analyses revealed the potential of the hpdBCA detection PCR sequence for initial phylogenetic classification, which allows assessment of C. difficile diversity in environmental samples via amplicon sequencing. Our findings furthermore showed that C. difficile strains isolated under antibiotic treatment from environmental samples were originally dominated by other strains according to PCR amplicon results. This provided evidence for selective cultivation of under-represented but antibiotic-resistant isolates. Thereby, we revealed a substantial bias in C. difficile isolation and research.IMPORTANCEClostridioides difficile is a main cause of diarrheic infections after antibiotic treatment with serious morbidity and mortality worldwide. Research on this pathogen and its virulence has focused on bacterial isolation from clinical specimens under antibiotic treatment, which implies a substantial bias in isolated strains. Comprehensive studies, however, require an unbiased strain collection, which is accomplished by isolation of C. difficile from diverse environmental samples and avoidance of antibiotic-based enrichment strategies. Thus, isolation can significantly benefit from our C. difficile-specific detection PCR, which rapidly verifies C. difficile presence in environmental samples and further allows estimation of the C. difficile diversity by using next-generation sequencing.
Subject(s)
Clostridioides difficile , Clostridium Infections , DNA, Environmental , Humans , Clostridioides , RNA, Ribosomal, 16S/genetics , Phylogeny , Anti-Bacterial Agents/pharmacology , Polymerase Chain Reaction , Clostridium Infections/microbiologyABSTRACT
BACKGROUND: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis. RESULTS: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC-2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU. CONCLUSIONS: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.
Subject(s)
Anti-Bacterial Agents , Bacteremia , Carbapenems , Klebsiella Infections , Klebsiella pneumoniae , Humans , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Retrospective Studies , Klebsiella Infections/microbiology , Klebsiella Infections/epidemiology , Klebsiella Infections/mortality , Klebsiella Infections/drug therapy , Risk Factors , Male , Female , Middle Aged , Aged , Bacteremia/microbiology , Bacteremia/mortality , Bacteremia/epidemiology , Bacteremia/drug therapy , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Phylogeny , Microbial Sensitivity Tests , Whole Genome Sequencing , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Virulence Factors/genetics , Aged, 80 and over , AdultABSTRACT
Candida auris, an emerging multidrug-resistant fungal pathogen discovered in Japan in 2009, poses a significant global health threat, with infections reported in about 25 countries. The escalation of drug-resistant strains underscores the urgent need for new treatment options. This study aimed to investigate the antifungal potential of 2,3,4,4a-tetrahydro-1H-xanthen-1-one (XA1) against C. auris, as well as its mechanism of action and toxic profile. The antifungal activity of XA1 was first evaluated by determining the minimum inhibitory concentration (MIC), time-kill kinetics and biofilm inhibition. In addition, structural changes, membrane permeability, reactive oxygen species (ROS) production, and in vitro and in vivo toxicity of C. auris after exposure to XA1 were investigated. The results indicated that XA1 exhibited an MIC of 50 µg/mL against C. auris, with time-kill kinetics highlighting its efficacy. Field emission scanning electron microscopy (FE-SEM) showed structural damage in XA1-treated cells, supported by increased membrane permeability leading to cell death. Furthermore, XA1 induced ROS production and significantly inhibited biofilm formation. Importantly, XA1 exhibited low cytotoxicity in human epidermal keratinocytes (HaCaT), with a cell viability of over 90 % at 6.25 µg/mL. In addition, an LD50 of 17.68 µg/mL was determined in zebrafish embryos 24 h post fertilization (hpf), with developmental delay observed at prolonged exposure at 6.25 µg/mL (48-96 hpf). These findings position XA1 as a promising candidate for further research and development of an effective antifungal agent.
Subject(s)
Antifungal Agents , Biofilms , Candida auris , Candidiasis , Drug Resistance, Fungal , Fluconazole , Microbial Sensitivity Tests , Reactive Oxygen Species , Zebrafish , Antifungal Agents/pharmacology , Biofilms/drug effects , Reactive Oxygen Species/metabolism , Humans , Animals , Fluconazole/pharmacology , Drug Resistance, Fungal/drug effects , Candida auris/drug effects , Candidiasis/drug therapy , Candidiasis/microbiology , Cell Membrane Permeability/drug effects , Cell Survival/drug effects , Cell Line , Keratinocytes/drug effects , Candida/drug effectsABSTRACT
A crucial pathogenic mechanism in many bacterial diseases is the ability to create biofilms. Biofilms are suspected to play a role in over 80 % of microbial illnesses in humans. In light of the critical requirement for efficient management of bacterial infections, researchers have explored alternative techniques for treating bacterial disorders. One of the most promising ways to address this issue is through the development of long-lasting coatings with antibacterial properties. In recent years, antibacterial treatments based on metallic nanoparticles (NPs) have emerged as an effective strategy in the fight over bacterial drug resistance. Zinc oxide nanoparticles (ZnO-NPs) are the basis of a new composite coating material. This article begins with a brief overview of the mechanisms that underlie bacterial resistance to antimicrobial drugs. A detailed examination of the properties of metallic nanoparticles (NPs) and their potential use as antibacterial drugs for curing drug-sensitive and resistant bacteria follows. Furthermore, we assess metal nanoparticles (NPs) as powerful agents to fight against antibiotic-resistant bacteria and the growth of biofilm, and we look into their potential toxicological effects for the development of future medicines.
Subject(s)
Anti-Bacterial Agents , Bacteria , Bacterial Infections , Biofilms , Metal Nanoparticles , Zinc Oxide , Biofilms/drug effects , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Anti-Bacterial Agents/pharmacology , Metal Nanoparticles/chemistry , Humans , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacteria/drug effects , Drug Resistance, Bacterial/drug effects , BiotechnologyABSTRACT
Candida Auris is an emerging fungal pathogen flagged by CDC as a serious global health threat among nosocomial infections in the recent times. As an evolving pathogen that often goes misidentified or unidentified under standard laboratory tests, it has the ability to cause fatal infections among the target population involving patients with serious medical conditions admitted to intensive care facilities, due to its capacity to resist anti-fungal treatment and the ability to persist in the hospital environment for long periods. The subject of this paper is to develop a deterministic model to study the transmission nature of Candida Auris wherein measures like apt admission screening methods with weekly screening follow-ups, transmission prevention, proper treatment protocols and environmental disinfection procedures are introduced as constant mitigating controls into the model initially which are later redefined as variable control functions during the optimal control analysis. The theory of optimal control implemented into the model helps us to understand the sensitivity of each control strategy upon the behaviour of each state variable. Further, cost-effectiveness analysis is rigorously conducted using incremental cost-effectiveness ratio (ICER) to identify and rank the control strategies involved based on their economic efficiency. Numerical simulation for the optimal control analysis is performed in MATLAB using the Forward-Backward Sweep Method and the findings are illustrated graphically.
ABSTRACT
Corynebacterium striatum is an emerging nosocomial pathogen. This is the first report showing the presence of three distinct multidrug resistant lineages of C. striatum among patients in a UK hospital. The presence of ErmX, Tet(W), Bla and AmpC proteins, and mutations in gyrA gene are associated with the resistance to clindamycin, doxycycline, penicillin and moxifloxacin, respectively. These strains are equipped with several corynebacterial virulence genes including two SpaDEF-type and a novel pilus gene cluster, which needs further molecular characterisation. This study highlights a need of developing an active surveillance strategy for routine monitoring and preventing potential cross-transmission among susceptible patients.
Subject(s)
Anti-Bacterial Agents , Corynebacterium Infections , Corynebacterium , Drug Resistance, Multiple, Bacterial , Phylogeny , Tertiary Care Centers , Humans , Corynebacterium/genetics , Corynebacterium/drug effects , Corynebacterium/isolation & purification , Corynebacterium/classification , Drug Resistance, Multiple, Bacterial/genetics , Corynebacterium Infections/microbiology , Corynebacterium Infections/epidemiology , United Kingdom/epidemiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Cross Infection/microbiology , Cross Infection/epidemiology , Male , Virulence Factors/genetics , Bacterial Proteins/genetics , FemaleABSTRACT
INTRODUCTION: Bacterial meningitis poses significant medical challenges due to its acute inflammatory nature and potential for severe neurological complications, emphasizing the need for prompt diagnosis and treatment. Limited data exists on its epidemiology and antimicrobial resistance trends among hospitalized patients in Saudi Arabia. This study aimed to investigate these factors at a tertiary care hospital over six years. METHODS: A retrospective analysis was conducted on cerebrospinal fluid samples results from 222 bacterial meningitis cases among hospitalized patients between 2018 and 2023. Demographic, clinical, microbiological data, and antibiotic susceptibility patterns were collected and analyzed. RESULTS: Pseudomonas aeruginosa (43%) was the predominant pathogen isolated. Neonates (16%) and children (47%) were most affected population. Nosocomial meningitis accounted for 92% of cases, mainly in the intensive care settings (50.45%). Extended-spectrum beta-lactamase was the leading resistance pattern (12.2%). Seasonal variation was observed, with a peak incidence in October-November. CONCLUSION: The study highlights the substantial burden of bacterial meningitis among hospitalized patients, especially among high-risk groups. Emerging antimicrobial resistance emphasizes the need for optimized surveillance and stewardship. Future prospective research employing molecular techniques across multiple centers in the country is warranted to enhance understanding and guide public health strategies in Saudi Arabia.
Subject(s)
Anti-Bacterial Agents , Cross Infection , Meningitis, Bacterial , Tertiary Care Centers , Humans , Saudi Arabia/epidemiology , Meningitis, Bacterial/epidemiology , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/drug therapy , Tertiary Care Centers/statistics & numerical data , Retrospective Studies , Female , Male , Child, Preschool , Child , Infant , Infant, Newborn , Adolescent , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Adult , Young Adult , Middle Aged , Cross Infection/epidemiology , Cross Infection/microbiology , Cross Infection/drug therapy , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Hospitalization/statistics & numerical data , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Aged , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification , Bacteria/genetics , IncidenceABSTRACT
Fourier-transform infrared (FTIR) spectroscopy has the potential to be used for bacterial typing and outbreak characterization. We evaluated FTIR for the characterization of an outbreak caused by Elizabethkingia miricola. During the 2020-2021 period, 26 isolates (23 clinical and 3 environmental) were collected and analyzed by FTIR (IR Biotyper) and core-genome MLST (cgMLST), in addition to antimicrobial susceptibility testing. FTIR spectroscopy and cgMLST showed that 22 of the isolates were related to the outbreak, including the environmental samples, with only one discordance between both methods. Then, FTIR is useful for E. miricola typing and can be easily implemented in the laboratory.