Metagenomic perspectives on antibiotic resistance genes in tap water: The environmental characteristic, potential mobility and health threat.

As an emerging environmental contaminant, antibiotic resistance genes (ARGs) in tap water have attracted great attention. Although studies have provided ARG profiles in tap water, research on their abundance levels, composition characteristics, and potential threat is still insufficient. Here, 9 household tap water samples were collected from the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in China. Additionally, 75 sets of environmental sample data (9 types) were downloaded from the public database. Metagenomics was then performed to explore the differences in the abundance and composition of ARGs. 221 ARG subtypes consisting of 17 types were detected in tap water. Although the ARG abundance in tap water was not significantly different from that found in drinking water plants and reservoirs, their composition varied. In tap water samples, the three most abundant classes of resistance genes were multidrug, fosfomycin and MLS (macrolide-lincosamide-streptogramin) ARGs, and their corresponding subtypes ompR, fosX and macB were also the most abundant ARG subtypes. Regarding the potential mobility, vanS had the highest abundance on plasmids and viruses, but the absence of key genes rendered resistance to vancomycin ineffective. Generally, the majority of ARGs present in tap water were those that have not been assessed and are currently not listed as high-threat level ARG families based on the World Health Organization Guideline. Although the current potential threat to human health posed by ARGs in tap water is limited, with persistent transfer and accumulation, especially in pathogens, the potential danger to human health posed by ARGs should not be ignored.

Metagenomics reveals the resistance patterns of electrochemically treated erythromycin fermentation residue.

Erythromycin fermentation residue (EFR) represents a typical hazardous waste produced by the microbial pharmaceutical industry. Although electrolysis is promising for EFR disposal, its microbial threats remain unclear. Herein, metagenomics was coupled with the random forest technique to decipher the antibiotic resistance patterns of electrochemically treated EFR. Results showed that 95.75% of erythromycin could be removed in 2 hr. Electrolysis temporarily influenced EFR microbiota, where the relative abundances of Proteobacteria and Actinobacteria increased, while those of Fusobacteria, Firmicutes, and Bacteroidetes decreased. A total of 505 antibiotic resistance gene (ARG) subtypes encoding resistance to 21 antibiotic types and 150 mobile genetic elements (MGEs), mainly including plasmid (72) and transposase (52) were assembled in EFR. Significant linear regression models were identified among microbial richness, ARG subtypes, and MGE numbers (r2=0.50-0.81, p< 0.001). Physicochemical factors of EFR (Total nitrogen, total organic carbon, protein, and humus) regulated ARG and MGE assembly (%IncMSE value = 5.14-14.85). The core ARG, MGE, and microbe sets (93.08%-99.85%) successfully explained 89.71%-92.92% of total ARG and MGE abundances. Specifically, gene aph(3')-I, transposase tnpA, and Mycolicibacterium were the primary drivers of the resistance dissemination system. This study also proposes efficient resistance mitigation measures, and provides recommendations for future management of antibiotic fermentation residue.

Metagenome-wide characterization of shared antimicrobial resistance genes in sympatric people and lemurs in rural Madagascar.

Background: Tracking the spread of antibiotic resistant bacteria is critical to reduce global morbidity and mortality associated with human and animal infections. There is a need to understand the role that wild animals in maintenance and transfer of antibiotic resistance genes (ARGs). Methods: This study used metagenomics to identify and compare the abundance of bacterial species and ARGs detected in the gut microbiomes from sympatric humans and wild mouse lemurs in a forest-dominated, roadless region of Madagascar near Ranomafana National Park. We examined the contribution of human geographic location toward differences in ARG abundance and compared the genomic similarity of ARGs between host source microbiomes. Results: Alpha and beta diversity of species and ARGs between host sources were distinct but maintained a similar number of detectable ARG alleles. Humans were differentially more abundant for four distinct tetracycline resistance-associated genes compared to lemurs. There was no significant difference in human ARG diversity from different locations. Human and lemur microbiomes shared 14 distinct ARGs with highly conserved in nucleotide identity. Synteny of ARG-associated assemblies revealed a distinct multidrug-resistant gene cassette carrying dfrA1 and aadA1 present in human and lemur microbiomes without evidence of geographic overlap, suggesting that these resistance genes could be widespread in this ecosystem. Further investigation into intermediary processes that maintain drug-resistant bacteria in wildlife settings is needed.

Sequencing Methods to Study the Microbiome with Antibiotic Resistance Genes in Patients with Pulmonary Infections.

Various antibiotic-resistant bacteria (ARB) are known to induce repeated pulmonary infections and increase morbidity and mortality. A thorough knowledge of antibiotic resistance is imperative for clinical practice to treat resistant pulmonary infections. In this study, we used a reads-based method and an assembly-based method according to the metagenomic next-generation sequencing (mNGS) data to reveal the spectra of ARB and corresponding antibiotic resistance genes (ARGs) in samples from patients with pulmonary infections. A total of 151 clinical samples from 144 patients with pulmonary infections were collected for retrospective analysis. The ARB and ARGs detection performance was compared by the reads-based method and assembly-based method with the culture method and antibiotic susceptibility testing (AST), respectively. In addition, ARGs and the attribution relationship of common ARB were analyzed by the two methods. The comparison results showed that the assembly-based method could assist in determining pathogens detected by the reads-based method as true ARB and improve the predictive capabilities (46% > 13%). ARG-ARB network analysis revealed that assembly-based method could promote determining clear ARGbacteria attribution and 101 ARGs were detected both in two methods. 25 ARB were obtained by both methods, of which the most predominant ARB and its ARGs in the samples of pulmonary infections were Acinetobacter baumannii (ade), Pseudomonas aeruginosa (mex), Klebsiella pneumoniae (emr), and Stenotrophomonas maltophilia (sme). Collectively, our findings demonstrated that the assembly-based method could be a supplement to the reads-based method and uncovered pulmonary infection-associated ARB and ARGs as potential antibiotic treatment targets.

Understanding the Evolution and Transmission Dynamics of Antibiotic Resistance Genes: A Comprehensive Review.

Antibiotic resistance poses a formidable challenge to global public health, necessitating comprehensive understanding and strategic interventions. This review explores the evolution and transmission dynamics of antibiotic resistance genes, with a focus on Bangladesh. The indiscriminate use of antibiotics, compounded by substandard formulations and clinical misdiagnosis, fuels the emergence and spread of resistance in the country. Studies reveal high resistance rates among common pathogens, emphasizing the urgent need for targeted interventions and rational antibiotic use. Molecular assessments uncover a diverse array of antibiotic resistance genes in environmental reservoirs, highlighting the complex interplay between human activities and resistance dissemination. Horizontal gene transfer mechanisms, particularly plasmid-mediated conjugation, facilitate the exchange of resistance determinants among bacterial populations, driving the evolution of multidrug-resistant strains. The review discusses clinical implications, emphasizing the interconnectedness of environmental and clinical settings in resistance dynamics. Furthermore, bioinformatic and experimental evidence elucidates novel mechanisms of resistance gene transfer, underscoring the dynamic nature of resistance evolution. In conclusion, combating antibiotic resistance requires a multifaceted approach, integrating surveillance, stewardship, and innovative research to preserve the efficacy of antimicrobial agents and safeguard public health.

The relationship between resistance evolution and carbon metabolism in Staphylococcus xylosus under ceftiofur sodium stress.

Staphylococcus xylosus has emerged as a bovine mastitis pathogen with increasing drug resistance, resulting in substantial economic impacts. This study utilized iTRAQ analysis to investigate the mechanisms driving resistance evolution in S. xylosus under ceftiofur sodium stress. Findings revealed notable variations in the expression of 143 proteins, particularly glycolysis-related proteins (TpiA, Eno, GlpD, Ldh) and peptidoglycan (PG) hydrolase Atl. Following the induction of ceftiofur sodium resistance in S. xylosus, the emergence of resistant strains displaying characteristics of small colony variants (SCVs) was observed. The transcript levels of TpiA, Eno, GlpD and Ldh were up-regulated, TCA cycle proteins (ICDH, MDH) and Atl were down-regulated, lactate content was increased, and NADH concentration was decreased in SCV compared to the wild strain. That indicates a potential role of carbon metabolism, specifically PG hydrolysis, glycolysis, and the TCA cycle, in the development of resistance to ceftiofur sodium in S. xylosus.

Infection on Frail Patients in the Intensive Care Unit: Insights From the PalMuSIC Study.

BACKGROUND: Along with population aging, frailty is also increasingly common in the intensive care unit (ICU). However, the impact of frailty on the infection incidence, the risk of multidrug-resistant (MDR) microorganisms, and the potential benefits of broad-spectrum antibiotics are still poorly studied. METHODS: This is a multicentric, prospective, observational study collecting data for 15 consecutive days of all consecutive adult patients admitted in each participating ICU. Exclusion criteria included admission for less than 24 hours or failure to obtain informed consent. The Clinical Frailty Score (CFS) was calculated both by the doctor and by the nurse in charge, and the patient's next of kin. Patients were considered frail if the mean of the three measured scores was ≥5. This is a post hoc analysis of the PALliative MUlticenter Study in Intensive Care (PalMuSIC) study. The Hospital de Vila Franca de Xira Ethics Committee approved the study (approval number: 63). RESULTS: A total of 335 patients from 23 Portuguese ICUs were included. Frailty was diagnosed in 20.9%. More than 60% of the patients had a diagnosis of infection during their ICU stay, either present on admission or hospital-acquired. This included 25 (35.7%) frail and 75 (28.3%) non-frail (p=0.23) patients diagnosed with infection. In 34 patients, MDR microorganisms were isolated, which were more common in frail patients (odds ratio (OR): 2.65, 95% confidence interval (CI): 1.3-5.6, p=0.018). Carbapenems were started in 37 (18.1%) patients, but after adjusting for frailty and severity, no clear mortality benefit of this strategy was noted (odds ratio for ICU mortality: 1.61, 95% confidence interval: 0.49-5.31, p=0.43; odds ratio for hospital mortality: 1.61, 95% confidence interval: 0.61-4.21, p=0.33). CONCLUSION: Frail patients had similar rates of infection to non-frail patients but were more prone to have MDR microorganisms as causative pathogens. The use of empirical therapy with large-spectrum antibiotics should be based on microbiological risk factors and not simply on the host characteristics.

When does antimicrobial resistance increase bacterial fitness? Effects of dosing, social interactions, and frequency dependence on the benefits of AmpC ß-lactamases in broth, biofilms, and a gut infection model.

One of the longstanding puzzles of antimicrobial resistance is why the frequency of resistance persists at intermediate levels. Theoretical explanations for the lack of fixation of resistance include cryptic costs of resistance or negative frequency-dependence but are seldom explored experimentally. ß-lactamases, which detoxify penicillin-related antibiotics, have well-characterized frequency-dependent dynamics driven by cheating and cooperation. However, bacterial physiology determines whether ß-lactamases are cooperative, and we know little about the sociality or fitness of ß-lactamase producers in infections. Moreover, media-based experiments constrain how we measure fitness and ignore important parameters such as infectivity and transmission among hosts. Here, we investigated the fitness effects of broad-spectrum AmpC ß-lactamases in Enterobacter cloacae in broth, biofilms, and gut infections in a model insect. We quantified frequency- and dose-dependent fitness using cefotaxime, a third-generation cephalosporin. We predicted that infection dynamics would be similar to those observed in biofilms, with social protection extending over a wide dose range. We found evidence for the sociality of ß-lactamases in all contexts with negative frequency-dependent selection, ensuring the persistence of wild-type bacteria, although cooperation was less prevalent in biofilms, contrary to predictions. While competitive fitness in gut infections and broth had similar dynamics, incorporating infectivity into measurements of fitness in infections significantly affected conclusions. Resistant bacteria had reduced infectivity, which limited the fitness benefits of resistance to infections challenged with low antibiotic doses and low initial frequencies of resistance. The fitness of resistant bacteria in more physiologically tolerant states (in biofilms, in infections) could be constrained by the presence of wild-type bacteria, high antibiotic doses, and limited availability of ß-lactamases. One conclusion is that increased tolerance of ß-lactams does not necessarily increase selection pressure for resistance. Overall, both cryptic fitness costs and frequency dependence curtailed the fitness benefits of resistance in this study.

Exceptions to the rule: When does resistance evolution not undermine antibiotic therapy in human bacterial infections?

The use of antibiotics to treat bacterial infections often imposes strong selection for antibiotic resistance. However, the prevalence of antibiotic resistance varies greatly across different combinations of pathogens and drugs. What underlies this variation? Systematic reviews, meta-analyses, and literature surveys capable of integrating data across many studies have tried to answer this question, but the vast majority of these studies have focused only on cases where resistance is common or problematic. Yet much could presumably be learned from the cases where resistance is infrequent or absent. Here we conducted a literature survey and a systematic review to study the evolution of antibiotic resistance across a wide range of pathogen-by-drug combinations (57 pathogens and 53 antibiotics from 15 drug classes). Using Akaike information criterion-based model selection and model-averaged parameter estimation we explored 14 different factors posited to be associated with resistance evolution. We find that the most robust predictors of high resistance are nosocomial transmission (i.e., hospital-acquired pathogens) and indirect transmission (e.g., vector-, water-, air-, or vehicle-borne pathogens). While the former was to be expected based on prior studies, the positive correlation between high resistance frequencies and indirect transmission is, to our knowledge, a novel insight. The most robust predictor of low resistance is zoonosis from wild animal reservoirs. We also found partial support that resistance was associated with pathogen type, horizontal gene transfer, commensalism, and human-to-human transmission. We did not find support for correlations between resistance and environmental reservoirs, mechanisms of drug action, and global drug use. This work explores the relative explanatory power of various pathogen and drug factors on resistance evolution, which is necessary to identify priority targets of stewardship efforts to slow the spread of drug-resistant pathogens.

Usefulness of dalbavancin in early discharge and nonhospitalization. It's time to throw your heart over the obstacle?

Introduction: Dalbavancin is a semisynthetic lipoglycopeptide long-acting antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Its features can be useful in the current healthcare scenario characterized by the shortage of available hospital beds. Materials methods and results: We implemented several actions in order to optimize the use of dalbavancin allowing an improvement strategy both from the healthcare system and the patient's perspective in two hospital settings. In the Emergency Department we hospitalized only patients who met the clinical criteria and not the logistic criteria (i.e., the need for antibiotic therapy infusion). During the years 2017-2023, this strategy was applied in 40 cases, thus avoiding 40 hospitalizations for a total saving of 280 days of hospitalization.In the Internal Medicine ward and surgery department when there was no longer any need for hospitalization, we discharged the patient as early as possible. During the years 2017-2023, this strategy was applied in 189 cases, saving at least 1,134 days of hospitalization. The outcome of the treated patients was favorable in 228 out of 229 patients (99.5%). Conclusions: Our experience using dalbavancin in ABSSSI has been very satisfactory overall. The efficacy was close to 100%. Minor adverse events of slight severity occurred rarely. At the same time, this strategy allowed a more efficient allocation of hospital beds. Dalbavancin presents an ideal pharmacodynamic/pharmacokinetic profile for the management of ABSSSI especially in settings where shortage of hospital beds is critical.

Opportunities to Improve Antibiotic Prescribing for Adults With Acute Sinusitis, United States, 2016-2020.

Background: Better understanding differences associated with antibiotic prescribing for acute sinusitis can help inform antibiotic stewardship strategies. We characterized antibiotic prescribing patterns for acute sinusitis among commercially insured adults and explored differences by patient- and prescriber-level factors. Methods: Outpatient encounters among adults aged 18 to 64 years diagnosed with sinusitis between 2016 and 2020 were identified by national administrative claims data. We classified antibiotic agents-first-line (amoxicillin-clavulanate or amoxicillin) and second-line (doxycycline, levofloxacin, or moxifloxacin)-and ≤7-day durations as guideline concordant based on clinical practice guidelines. Modified Poisson regression was used to examine the association between patient- and prescriber-level factors and guideline-concordant antibiotic prescribing. Results: Among 4 689 850 sinusitis encounters, 53% resulted in a guideline-concordant agent, 30% in a guideline-discordant agent, and 17% in no antibiotic prescription. About 75% of first-line agents and 63% of second-line agents were prescribed for >7 days, exceeding the length of therapy recommended by clinical guidelines. Adults with sinusitis living in a rural area were less likely to receive a prescription with guideline-concordant antibiotic selection (adjusted risk ratio [aRR], 0.92; 95% CI, .92-.92) and duration (aRR, 0.77; 95% CI, .76-.77). When compared with encounters in an office setting, urgent care encounters were less likely to result in a prescription with a guideline-concordant duration (aRR, 0.76; 95% CI, .75-.76). Conclusions: Opportunities still exist to optimize antibiotic agent selection and treatment duration for adults with acute sinusitis, especially in rural areas and urgent care settings. Recognizing specific patient- and prescriber-level factors associated with antibiotic prescribing can help inform antibiotic stewardship interventions.

HAMLET, a human milk protein-lipid complex, modulates amoxicillin induced changes in an ex vivo biofilm model of the oral microbiome.

Challenges from infections caused by biofilms and antimicrobial resistance highlight the need for novel antimicrobials that work in conjunction with antibiotics and minimize resistance risk. In this study we investigated the composite effect of HAMLET (human alpha-lactalbumin made lethal to tumor cells), a human milk protein-lipid complex and amoxicillin on microbial ecology using an ex vivo oral biofilm model with pooled saliva samples. HAMLET was chosen due to its multi-targeted antimicrobial mechanism, together with its synergistic effect with antibiotics on single species pathogens, and low risk of resistance development. The combination of HAMLET and low concentrations of amoxicillin significantly reduced biofilm viability, while each of them alone had little or no impact. Using a whole metagenomics approach, we found that the combination promoted a remarkable shift in overall microbial composition compared to the untreated samples. A large proportion of the bacterial species in the combined treatment were Lactobacillus crispatus, a species with probiotic effects, whereas it was only detected in a minor fraction in untreated samples. Although resistome analysis indicated no major shifts in alpha-diversity, the results showed the presence of TEM beta-lactamase genes in low proportions in all treated samples but absence in untreated samples. Our study illustrates HAMLET's capability to alter the effects of amoxicillin on the oral microbiome and potentially favor the growth of selected probiotic bacteria when in combination. The findings extend previous knowledge on the combined effects of HAMLET and antibiotics against target pathogens to include potential modulatory effects on polymicrobial biofilms of human origin.

Distribution and community structure of antibiotic resistance genes in the Three Gorges Reservoir Area.

Antibiotic resistance genes (ARG) are widespread across various regions. While several studies have investigated the distribution of antibiotic resistance in natural environments, the occurrence and diversity of ARGs in the Three Gorges Reservoir have not been fully elucidated. In this study, we employed metagenomic sequencing techniques to investigate the abundance, diversity, and influencing factors of ARGs in the ecosystem of the Three Gorges Reservoir. A total of 874 ARGs, 20 antibiotic classes, and 6 resistance mechanisms were detected. The dominant ARG is the macB, the dominant antibiotic class is multidrug resistance (MDR), and the dominant resistance mechanism is antibiotic efflux. The microorganisms with the highest contribution to ARGs are Betaproteobacteria and Gammaproteobacteria. In this region, pH and NH4+ concentration were significantly negatively correlated with the relative abundance of most ARGs, while NO3- concentration and TN were significantly positively correlated with the relative abundance of most ARGs. The results indicate that the Three Gorges Reservoir constitutes a significant reservoir of ARGs. By studying the distribution of ARGs in the sediments of the Three Gorges Reservoir Area and the relationship between environmental factors and ARGs, we can more comprehensively understand the pollution status of ARGs in this area, and provide theoretical support for subsequent treatment.

Evaluation of EUCAST rapid antimicrobial susceptibility test directly from positive blood culture for Pseudomonas aeruginosa.

In this study, we evaluated the performance of the EUCAST RAST method on a collection of 154 clinical strains of P. aeruginosa, including strains resistant to ceftazidime and carbapenems. While the test is convenient for routine laboratories, we observed significant rates of VME (ranging from 0.0 to 15.0%) and ME (ranging from 1.3 to 16.3%) after 6 h, particularly for key antibiotics such as ceftazidime, piperacillin/tazobactam, and meropenem. Extending the incubation time to 8 h may improve results (CA ranging from 87.2 to 99%), but caution is required in interpretation due to persistence of VME (ranging from 0.0 to 15.6%) and ME (ranging from 0.0 to 11.7%).

Sources, interactions, influencing factors and ecological risks of microplastics and antibiotic resistance genes in soil: A review.

Microplastics (MPs) and antibiotic resistance genes (ARGs) are gaining increasing attention as they pose a threat to the ecological environment and human health as emerging contaminants. MPs has been proved to be a hot spot in ARGs, and although it has been extensively studied in water environment, the results of bibliometrics statistical analysis in this paper showed that relevant studies in soil ecological environment are currently in the initial stage. In view of this, the paper provides a systematic review of the sources, interactions, influencing factors, and ecological risks associated with MPs and ARGs in soil environments. Additionally, the mechanism and influencing factors of plastisphere formation and resistance are elaborated in detail. The MPs properties, soil physicochemical properties, soil environmental factors and agricultural activities are the primarily factors affecting the interaction between MPs and ARGs in soil. Challenges and development directions of related research in the future are also prospected. It is hoped that the review could assist in a deeper comprehension and exploration of the interaction mechanism between MPs and ARGs in soil as well as the function of MPs in the transmission process of ARGs among diverse environmental media and organisms, and provide theory basis and reference for the MPs and ARGs pollution control and remediation in soil.

Genomic diversity, antibiotic resistance, and virulence in South African Enterococcus faecalis and Enterococcus lactis isolates.

This study presents the empirical findings of an in-depth genomic analysis of Enterococcus faecalis and Enterococcus lactis isolates from South Africa. It offers valuable insights into their genetic characteristics and their significant implications for public health. The study uncovers nuanced variations in the gene content of these isolates, despite their similar GC contents, providing a comprehensive view of the evolutionary diversity within the species. Genomic islands are identified, particularly in E. faecalis, emphasizing its propensity for horizontal gene transfer and genetic diversity, especially in terms of antibiotic resistance genes. Pangenome analysis reveals the existence of a core genome, accounting for a modest proportion of the total genes, with 2157 core genes, 1164 shell genes, and 4638 cloud genes out of 7959 genes in 52 South African E. faecalis genomes (2 from this study, 49 south Africa genomes downloaded from NCBI, and E. faecalis reference genome). Detecting large-scale genomic rearrangements, including chromosomal inversions, underscores the dynamic nature of bacterial genomes and their role in generating genetic diversity. The study uncovers an array of antibiotic resistance genes, with trimethoprim, tetracycline, glycopeptide, and multidrug resistance genes prevalent, raising concerns about the effectiveness of antibiotic treatment. Virulence gene profiling unveils a diverse repertoire of factors contributing to pathogenicity, encompassing adhesion, biofilm formation, stress resistance, and tissue damage. These empirical findings provide indispensable insights into these bacteria's genomic dynamics, antibiotic resistance mechanisms, and virulence potential, underlining the pressing need to address antibiotic resistance and implement robust control measures.

Effectiveness of de-implementation of low-value healthcare practices: an overview of systematic reviews.

BACKGROUND: Reducing low-value care (LVC) is crucial to improve the quality of patient care while increasing the efficient use of scarce healthcare resources. Recently, strategies to de-implement LVC have been mapped against the Expert Recommendation for Implementing Change (ERIC) compilation of strategies. However, such strategies' effectiveness across different healthcare practices has not been addressed. This overview of systematic reviews aimed to investigate the effectiveness of de-implementation initiatives and specific ERIC strategy clusters. METHODS: We searched MEDLINE (Ovid), Epistemonikos.org and Scopus (Elsevier) from 1 January 2010 to 17 April 2023 and used additional search strategies to identify relevant systematic reviews (SRs). Two reviewers independently screened abstracts and full texts against a priori-defined criteria, assessed the SR quality and extracted pre-specified data. We created harvest plots to display the results. RESULTS: Of 46 included SRs, 27 focused on drug treatments, such as antibiotics or opioids, twelve on laboratory tests or diagnostic imaging and seven on other healthcare practices. In categorising de-implementation strategies, SR authors applied different techniques: creating self-developed strategies (n = 12), focussing on specific de-implementation strategies (n = 14) and using published taxonomies (n = 12). Overall, 15 SRs provided evidence for the effectiveness of de-implementation interventions to reduce antibiotic and opioid utilisation. Reduced utilisation, albeit inconsistently significant, was documented in the use of antipsychotics and benzodiazepines, as well as in laboratory tests and diagnostic imaging. Strategies within the adapt and tailor to context, develop stakeholder interrelationships, and change infrastructure and workflow ERIC clusters led to a consistent reduction in LVC practices. CONCLUSION: De-implementation initiatives were effective in reducing medication usage, and inconsistent significant reductions were observed for LVC laboratory tests and imaging. Notably, de-implementation clusters such as change infrastructure and workflow and develop stakeholder interrelationships emerged as the most encouraging avenues. Additionally, we provided suggestions to enhance SR quality, emphasising adherence to guidelines for synthesising complex interventions, prioritising appropriateness of care outcomes, documenting the development process of de-implementation initiatives and ensuring consistent reporting of applied de-implementation strategies. REGISTRATION: OSF Open Science Framework 5ruzw.

Antimicrobial resistance, biofilm formation, and molecular detection of efflux pump and biofilm genes among Klebsiella pneumoniae clinical isolates from Northern Jordan.

The current study aimed to investigate the antimicrobial susceptibility profiles, biofilm production capabilities, and the prevalence of efflux pump and biofilm-associated genes among Klebsiella pneumoniae clinical isolates. One hundred sixty-seven K. pneumoniae isolates were collected from microbiology laboratories in Northern Jordan hospitals. Antimicrobial susceptibility was tested using the Kirby-Bauer method. The double-disk synergy test was used to detect the extended-spectrum beta-lactamase (ESBL) phenotype. PCR was used to detect the frequency of acrAB, tolC, and mdtk efflux pump genes and fimH-1, mrkA, and mrkD biofilm-associated genes among the isolates. The highest nonsusceptibility was observed against azithromycin (87.4 %) and nitrofurantoin (85.0 %). Among the isolates, 75.4 % and 92.2 % were multidrug resistant and produced biofilms, respectively. Efflux pump genes acrAB, tolC, and mdtK were found in 96.4 %, 95.2 %, and 90.4 % of the isolates, respectively. Biofilm-associated genes mrkD, mrkA, and fimH-1 were found in 92.2 %, 89.2 %, and 88.6 % of the isolates, respectively. The presence of the mrkA was significantly associated with biofilm formation. Overall, high percentages of multi-drug resistance, efflux pump, and biofilm-associated genes were observed among the isolates. Subsequent studies are recommended to monitor changes in the prevalence of resistance phenotypes and genotypes of isolates.

Endovascular Aortic Repair of an Infective Native Aortic Aneurysm.

An infective native aortic aneurysm (INAA) is a rare, life-threatening, and complex disease. Therefore, the diagnosis and treatment of INAA remain uncertain. We describe the case of a 64-year-old man who had abdominal pain and a fever for more than one week. We diagnosed him with INAA on the basis of the clinical presentation, laboratory findings, and computed tomography (CT) images. After administering preoperative antibiotic therapy for four weeks, we performed endovascular aortic repair (EVAR). He then received antibiotic treatment for 12 months postoperatively. After successful treatment of an INAA with endovascular aortic repair, the patient had no recurrence for more than six years after the end of antibiotic therapy.

A Systematic Review of Community-Acquired Pneumonia in Indian Adults.

This systematic review aimed to consolidate findings on the etiology of community-acquired pneumonia (CAP) among Indian adults. We adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines 2020 and conducted a comprehensive search across databases including PubMed, Scopus-Elsevier, and hand-searched reference lists using key terms such as "Community-Acquired Pneumonia," "CAP," "Indian," and "adults." Articles published between January 2010 and January 2024 were included, with exclusions for studies involving pediatric populations, non-Indian patients, or those published before 2010. From an initial pool of 344 articles, duplicates were removed and titles and abstracts were screened, resulting in nine studies meeting the inclusion criteria. The analysis of pooled data comprising 1,643 Indian adult participants revealed the following pathogen distribution: Streptococcus pneumoniae was the most common organism, accounting for 33% of the cases. This was followed by Klebsiella pneumoniae at 23%, Staphylococcus aureus at 10%, Mycoplasma pneumoniae and Legionella pneumophila each at 7%, and Chlamydia pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa each at 4%. Notably, the review highlights a rising incidence of K. pneumoniae in CAP cases, which is a significant concern and should be considered when treating CAP patients in India. The findings emphasize the importance of comprehensive diagnostic testing, including advanced methods such as bronchoalveolar lavage, urinary antigen tests, serology for atypical pathogens, and enzyme-linked immunosorbent assays, to improve diagnostic yield and guide targeted antibiotic therapy. This review underscores the need for updated empirical treatment guidelines that account for dominant pathogens. Future research should focus on employing advanced diagnostic methods to enhance understanding of CAP etiology.