SASPI Ltd.
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Performance of two combination disk methods as confirmation for ESBL and AmpC presence in clinical Enterobacterales isolates
Authors: L. Doornekamp
Abstract
Purpose: Guidelines recommend the use of a combination disk method (CDM) including cefepime and clavulanic acid as a confirmation method for ESBL detection. However, an alternative CDM containing cloxacillin (combining ceftazidime and cefotaxime with clavulanic acid and/or cloxacillin), is not only able to confirm ESBL presence, but also to provide information about AmpC production. We aim to show non-inferiority of the cloxacillin-CDM compared to the cefepime-CDM.
Methods: We collected 102 individual clinical Enterobacterales isolates that were positive in the ESBL screening with the VITEK II. Phenotypic confirmation was performed with a cefepime-CDM and a cloxacillin-CDM (Rosco®). These results were compared with the results of a multiplex ESBL real-time PCR and an in-house developed conventional AmpC PCR.
Results: Twenty-eight% of the isolates were positive in the ESBL PCR (CTX-M, SHV-2, TEM-3). The results of cefepime-CDM and cloxacillin-CDM were concordant with the ESBL PCR in respectively 99 and 94 %. The cefepime-CDM had a sensitivity of 100 % (95 % confidence interval (CI) 88,1-100) and specificity of 98,6 % (95 % CI 92,6-100). The cloxacillin-CDM had a sensitivity of 96,6 (95 % CI 82,2-99,9) and a specificity of 93,2 % (95 % CI 84,7-97,7). The cloxacillin-CDM in the group I Enterobacterales compared to the AmpC PCR had a sensitivity of 92 % (95 % CI 62-100) and a specificity of 100 % (95 % CI 77-100).
Conclusion: Both cefepime-CDM and cloxacillin-CDM performed well as ESBL confirmation methods. Therefore, we suggest to add the cloxacillin-CDM as an alternative ESBL confirmation method to AMR detection guidelines in clinical settings.
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Evaluation of optimized Real time-PCR HRM assay and SPR-based biosensor for noninvasive isolation of H. pylori and Clarithromycin resistance 23S-SNP subtype
Authors: Atena Abedi Maghami
Abstract
High Resolution Melting analysis is a highly sensitive molecular method, and the plasmonic-based sensor is a convenient test, be clinically elicited, in simultaneous H. pylori control and the prevention of Clarithromycin resistant strains related to SNPs. Comparing gold standard tests, we evaluated HRMA and the SPR-based biosensor in regard to noninvasive forms of H. pylori management, and explored resistance through a possible mechanism by 23S-SNPs.We optimized Realtime-PCR HRM analysis, and SPR-based biosensor. Referring to CTs ± 38, isolation sensitivity was evaluated at 74 %. Compared to the reference-test, results agreements were assessed with a kappa of 43 %, p = 0.001. Within melting plots (differentiation plot), the strains were detectable at Tms ranging from 81.5 to 82.3 (°C). Contributing to phenotypically determined resistant strains for 44 %, there was a wide distribution among resistant variants assessed through Tms of 82, 81.5, 82, 82.3, and 81.7 (°C). A2143C was the only mutation isolated at a specific Tm of 82.3°C; kappa = 8 %, p = 0.3. For sensing analysis, including 100 % specificity, this sensor type was associated with lower sensitivity of 49 %, kappa=19 %, p = 0. 01. For SNP, specificity, kappa value, and p-value of isolation were 100 %, 100 %, and 0.001. Lod was 0.003 ng/mL and 0.03 µg/mL for HRM assay and sensing analysis. In our evaluations, applicable priority of HRM analysis was the higher estimation of sensitivity; its differentiation plot was completely covered the results of strain variability regarding specific SNPs detection. Consistent with the biosensor for isolation of SNP, the development of biosensors is the necessity for noninvasive H. pylori detection.
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Multifocal Candida infections in cancer patients face dual challenges of surgical risk and drug resistance
Authors: Atena Abedi Maghami
Abstract
Multifocal Candida infections represent a serious threat for cancer patients, often leading to increased mortality. This study investigates the risk factors and outcomes for multifocal Candida infections compared to single-site infections and evaluates species distribution and antifungal susceptibility patterns. Fifty-seven Candida isolates were obtained from 23 cancer patients with multifocal infections. Another 57 isolates were collected from 57 matched patients with single-site infections. Germ tube test and CHROMAgar medium were used for species identification. Antifungal susceptibility of amphotericin B, caspofungin, fluconazole, and voriconazole was determined following the Clinical and Laboratory Standard Institute (CLSI), M60-Ed2. Of the 80 cancer patients, the majority of cases involved solid tumors (85.0 %), with gastrointestinal cancer being the most common in both multifocal and single-focal groups (p = 0.207). Significantly more patients with multifocal infections were admitted to the ICU compared to those with single-site infections (60.9 % versus 34.0 %, p = 0.029). Surgical procedures independently increased the risk for multifocal infections (OR: 10.506, p = 0.047). Multifocal infections had a significantly higher mortality rate than single-site infections (69.6 % versus 42.1 %, OR: 3.143, p = 0.026). Non-albicans Candida (NAC) species constituted 57.9 % (n = 66) of the 114 isolates, with Candida glabrata being the most prevalent (n = 49, 43.0 %). All tested antifungals revealed high resistance rates, particularly amphotericin B (79.8 %) and fluconazole (53.5 %). NAC species demonstrated significantly higher resistance rates than Candida albicans. Multifocal Candida infections in cancer patients showed higher mortality, with surgical procedures and ICU admission as key risk factors. The increasingly prevalent resistant NAC species, particularly C. glabrata, need accurate identification, antifungal stewardship, and new therapeutic strategies.
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Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples offers diagnostic utility in bacteriologically negative pulmonary tuberculosis
Authors: Hua Xiao
Abstract
Rapid diagnosing Mycobacterium tuberculosis (M. tb) in patients with pulmonary tuberculosis (PTB) cases is critical, particularly in cases without bacteriologically confirmed disease, as it enables timely treatment initiation and can thus interrupt further disease transmission. In this study, the utility of metagenomic next-generation sequencing (mNGS) as a diagnostic tool was evaluated using samples of bronchoalveolar lavage fluid (BALF) samples from 300 bacteriologically negative PTB (BN-PTB) patients hospitalized from January 2020 through December 2023. The diagnostic performance of mNGS was compared to that of acid-fast staining (AFS), conventional Roche culture, and the Xpert method among these BN-PTB patients, using clinical diagnosis as the gold standard. The final analyses enrolled 112 PTB patients and 188 non-PTB cases. These analyses revealed that mNGS-based M. tb detection yields a sensitivity of 94.64 % (106/112), a specificity of 98.94 % (186/188), a positive predictive value (PPV) of 98.15 % (106/108), and a negative predictive value (NPV) of 96.88 % (186/192). This mNGS approach outperformed the AFS, Roche culture, and Xpert methods in terms of sensitivity, specificity, PPV, and NPV (p < 0.05). The superior diagnostic performance of this approach was further supported by its area under the curve and corresponding confidence intervals. Together, these data demonstrate that mNGS can improve the detection of M. tb in BALF samples from BN-PTB patients with high levels of speed, sensitivity, and specificity. This mNGS approach may thus be a valuable diagnostic tool for the rapid detection of M. tb in BN-PTB, providing a foundation for the precision diagnosis and treatment of PTB in the future.
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CO2 concentration testing as a quick estimate of natural ventilation effectiveness in primary healthcare: experience in war-affected, resource-limited settings
Authors: M. Dolynska
Abstract
Ventilation remains an important component of infection prevention and control programmes. Natural ventilation, as the most affordable measure to control airborne transmission of pathogens, is a crucial area of focus. However, applying natural ventilation encounters challenges in routine practice, especially in emergencies. This study, which aimed to review the most efficient natural ventilation regimen, was performed in Autumn 2023 in two heavily war-affected primary care facilities in Ukraine. The study demonstrated the operational advantage of a regimen built upon a simple approach, where personnel opened windows only after observing an increased CO2 concentration. This solution has obvious disadvantages, being reactive rather than proactive and requiring continuous monitoring of CO2 concentration; it turned out to be more acceptable to busy healthcare workers than regimens developed explicitly for each office, considering ventilation rate and workload. Patients’ complaints about feeling cold in the offices may be a substantial obstacle to the formal use of natural ventilation. Reported results were considered an acceptable temporary compromise for initiating a natural ventilation policy. Further improvement will require personnel training and raising awareness about reasonable prevention interventions for airborne pathogens among patients.
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Molecular characterization of metallo-beta-lactamase producers among carbapenem-resistant Pseudomonas aeruginosa from clinical samples in a tertiary care hospital, Lucknow, India.
Authors: Ahmad N et al
Abstract
Pseudomonas aeruginosa is a significant opportunistic pathogen in healthcare-associated infections. Its intrinsic resistance and ability to acquire resistance genes pose therapeutic challenges, particularly with the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains. This study aimed to assess the prevalence, antimicrobial susceptibility, and metallo-β-lactamase (MBL) resistance genes (blaNDM, blaOXA48) in P. aeruginosa isolates from clinical samples over 14 months. A total of 4410 clinical samples were processed, yielding 241 non-duplicate P. aeruginosa isolates. Antimicrobial susceptibility testing (AST) identified MDR, XDR, and PDR isolates. Carbapenemase production was detected using the eCIM test, and blaNDM and blaOXA48 genes were identified via PCR. Among the 241 isolates, 128 (53.1%) were from female patients and 113 (46.9%) from males. The most common sample sources were pus 111 (46.1%), sputum 36 (14.9%), and urine 35 (14.5%). The highest prevalence was observed in the Medicine department (45, 18.7%) and TB & Chest (42, 17.4%). Inpatients contributed 126 (52.3%) isolates, while 115 (47.7%) were from outpatients. AST showed the highest sensitivity to piperacillin/tazobactam (70.2%), piperacillin (67.2%), and tobramycin (67.6%), while imipenem (47.7%) and ceftazidime (33.6%) exhibited the lowest sensitivity. MDR was identified in 88 (36.5%) isolates, XDR in 29 (12.0%), and PDR in 9 (3.7%). MDR isolates were most common in pus (33, 13.6%), while XDR and PDR were frequently found in bronchoalveolar lavage (6, 2.4%) and urine (3, 1.2%), respectively. Among 20 eCIM-positive isolates, all carried the blaNDM gene, and 17 (85.0%) harbored blaOXA48. Males accounted for 70.0% of blaNDM and 70.6% of blaOXA48 cases. The highest prevalence of blaNDM (35.0%) was in the 41-60 age group, while blaOXA48 was equally distributed between the 20-40 and 41-60 age groups (35.3% each). Sputum (25.0% blaNDM, 23.5% blaOXA48) and urine (20.0% each) were the most common specimen sources. This study demonstrates the presence of antimicrobial resistance in P. aeruginosa isolates, including MDR, XDR, and PDR strains. The detection of carbapenemase-producing isolates carrying blaNDM and blaOXA-48 genes emphasizes the importance of effective infection control measures, antimicrobial stewardship, and ongoing surveillance to monitor and manage resistance trends.
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Plasmid-borne mcr-1 and replicative transposition of episomal and chromosomal bla(NDM-1), bla(OXA-69), and bla(OXA-23) carbapenemases in a clinical Acinetobacter baumannii isolate.
Authors: Mmatli M et al
Abstract
A multidrug-resistant clinical Acinetobacter baumannii isolate with resistance to most antibiotics was isolated from a patient at an intensive care unit. The genetic environment, transcriptome, mobile, and resistome were characterized. The MicroScan system, disc diffusion, and broth microdilution were used to determine the resistance profile of the isolate. A multiplex PCR assay was also used to screen for carbapenemases and mcr-1 to -5 resistance genes. Efflux-pump inhibitors were used to evaluate efflux activity. The resistome, mobilome, epigenome, and transcriptome were characterized. There was phenotypic resistance to 22 of the 25 antibiotics tested, intermediate resistance to levofloxacin and nalidixic acid, and susceptibility to tigecycline, which corresponded to the 27 resistance genes found in the genome, most of which occurred in multiple copies through replicative transposition. A plasmid-borne (pR-B2.MM_C3) mcr-1 and chromosomal blaPER-7, blaOXA-69, blaOXA-23 (three copies), blaADC-25, blaTEM-1B, and blaNDM-1 were found within composite transposons, ISs, and/or class 1 and 2 integrons on genomic islands. Types I and II methylases and restriction endonucleases were in close synteny to these resistance genes within the genomic islands; chromosomal genomic islands aligned with known plasmids. There was a closer evolutionary relationship between the strain and global strains but not local or regional strains; the resistomes also differed. Significantly expressed/repressed genes (6.2%) included resistance genes, hypothetical proteins, mobile elements, methyltransferases, transcription factors, and membrane and efflux proteins. The genomic evolution observed in this strain explains its adaptability and pandrug resistance and shows its genomic plasticity on exposure to antibiotics. Importance: A pandrug-resistant pathogen that was susceptible to only a single antibiotic, tigecycline, was isolated from a middle-aged patient in an ICU. This pathogen contained two plasmids and had a chromosome that contained portions that were integrated externally from plasmids. These genomic islands were rich with resistance genes, mobile genetic elements, and restriction-modification systems that protected the pathogen and facilitated gene regulation. The strain contained 35 resistance genes and 12 virulence genes. The strain was of closer evolutionary distance to several international strains suggesting that it was imported into South Africa. However, its resistome was unique, suggesting an independent evolution on exposure to antibiotic therapy mediated by epigenomic factors and MGE transposition events. The varied mechanisms available to this strain to overcome antibiotic resistance and spread to other areas and/or transfer its resistance determinants are worrying. This is ultimately a risk to public health, evincing the need for antibiotic stewardship.
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Continued T12 transmission and shared antibiotic resistance during 2018-2023 Vibrio cholerae outbreaks in Cameroon.
Authors: Ngomtcho SCH et al
Abstract
Seventh pandemic Vibrio cholerae was first identified in Cameroon in 1971, causing several sporadic disease clusters with few cases. More recent years have seen larger cholera outbreaks, but the mechanism behind these periodic outbreaks is poorly understood, and it is unclear the degree to which antibiotic resistant strains contribute to disease burden and spread. Whole genome sequencing was used to characterize 13 V. cholerae isolates from the 2018-2019, 2020, and 2021-2023 cholera epidemics in Cameroon. All these isolates belonged to the T12 lineage, and most showed the same antimicrobial resistance (AMR) pattern regardless of year. This suggests that cholera outbreaks in Cameroon are, at least in part, a continuation of the outbreaks previously reported in 2018 and as far back as 2012. This finding has important implications for cholera management since it suggests the ongoing presence of pathogenic cholera even in years with few reported cases. Similarly, the AMR results suggest the need for new treatment approaches, as resistance to many common antibiotics was found even within the limited sample set. As such, whole genome sequencing should be implemented in low-income countries such as Cameroon to improve disease surveillance and to detect and predict pathogen antibiotic resistance profiles.
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A mixed-method study on antimicrobial resistance infection drivers in neonatal intensive care units: pathways, risks, and solutions.
Authors: Yeshiwas AG et al
Abstract
Background: Antimicrobial resistance (AMR) in neonatal intensive care units (NICUs) complicates treatment of healthcare-associated infections, causing high morbidity and mortality, especially among low-birth-weight and critically ill infants. This study evaluates AMR prevalence, risk factors, outcomes, and infection control measures at Felege Hiwot Hospital, aiming to guide clinical practices, antimicrobial stewardship, and improved neonatal health outcomes.
Methods: This mixed-methods study (Oct 2022-Jun 2023) assessed AMR in NICU neonates by analyzing 420 blood samples, environmental swabs, and staff insights. Bivariable and multivariable regressions identified significant variables, and content analysis was used for qualitative data.
Results: Out of 420 samples, 35% tested positive for AMR pathogens, with Coagulase-Negative Staphylococci (16.7%), Klebsiella pneumoniae (12.9%), and Acinetobacter spp. (5.6%) being the most prevalent. Resistance rates for Gentamicin, Cotrimoxazole, and Ciprofloxacin were alarmingly high (98-100%), while Amikacin demonstrated low resistance (3.0-5.56%), indicating potential efficacy. Among the neonates admitted, 91.8% survived, and 8.2% succumbed. Risk factor analysis revealed that improper PPE usage (AOR 3.90, p < 0.001), non-functional handwashing sinks (AOR 3.20, p < 0.001), and inadequate disinfection practices (AOR 2.70, p < 0.001) were strongly associated with microbial contamination. Environmental factors, including cockroach presence (AOR 1.80, p = 0.040) and high traffic flow (AOR 2.10, p = 0.005), were also significant contributors. The qualitative data analysis confirmed that improper PPE use, inadequate disinfection practices, pest control challenges, and non-functional handwashing sinks significantly contributed to microbial contamination risks in the NICU, aligning with the quantitative findings.
Conclusions: This study underscores key factors driving AMR in NICUs, such as inadequate IPC practices and environmental contamination, alongside high resistance to Cotrimoxazole and Ciprofloxacin. Amikacin shows promise as an effective treatment for CONS. Urgent actions, including strengthened IPC measures, staff training, and environmental management, are crucial to combat AMR, ensuring improved neonatal care and outcomes.
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Awareness and perception of antimicrobial stewardship program among healthcare professionals in the hospitals of ministry of health and population, Egypt: antimicrobial stewardship toolkit survey.
Authors: Abd El Azeem Khalaf YM et al
Abstract
Background: Antimicrobial resistance (AMR) has been recognized by international policymakers as a serious threat due to its current and projected influence on global population health, healthcare expenditures and gross domestic product (GDP). The present work aimed to assess the awareness, perceptions, and practices of healthcare professionals regarding the implementation of the Antimicrobial Stewardship program (ASP).
Methods: A cross-sectional study was conducted among 310 health care professionals. A self-administered questionnaire based on Antimicrobial Stewardship Toolkit for Acute and Long-Term Care Facilities; Greater New York Hospital Association (GNYAHA) was used to assess perceptions and knowledge about AMR and automatic selective perception.
Results: A total of 310 healthcare professionals participated in the study, of which 60.6% were females, with a mean age of 37.32 ± 8.71, mean years of working of 6.0 ± 5.95 and mean years of experience of 7.97 ± 7.14. The mean scores for AMR awareness, antibiotic (AB) prescribing practices, ASP perception, and intervention beliefs were 73.05 ± 11.21, 32.97 ± 8.22, 52.85 ± 13.99, and 18.24 ± 2.71, respectively. Bivariate analysis showed that profession, primary work unit, staff position significantly affect the AMR awareness and ASP perception, while only staff position affect intervention beliefs. The Multivariate linear regression showed that working in pharmacy, ABs prescribing practice and ASP perception were independent predictors of AMR awareness. Years of work in hospital, AMR awareness and ASP perception were the independent predictors of ABs prescribing practice. AMR awareness, ABs prescribing practice and intervention beliefs were independent predictors of ASP perception while ASP perception was the only independent predictors of intervention beliefs.
Conclusions: The study found a high level of awareness and practice regarding AMR and ASP among healthcare professionals. Pharmacists had higher levels of AMR awareness and ASP perception than physician in different specialities. Levels of AMR awareness, ABs prescribing practice, ASP perception and intervention beliefs affect each other in different ways. Linear regression supported our findings that pharmacists had a higher level of AMR awareness, while years of work in hospital had a significant effect on ABs prescribing practice.
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Major blood stream infection-causing bacterial pathogens, antimicrobial resistance patterns and trends: a multisite retrospective study in Asmara, Eritrea (2014-2022).
Authors: Andemivchael YG et al
Abstract
Background: An important knowledge gap exists on the epidemiology of blood stream infections (BSIs) in low-middle-income countries (LMICs). In this retrospective analysis, the etiology, antimicrobial resistance (AMR) and trends of BSIs in Eritrea were evaluated.
Methods: The study reviewed 9-year records (January 2014- December 2022) of 3153 patients with blood culture results available in the National Health Laboratory (NHL) archives. Relevant data included age, sex, hospital/care center, and year.
Result: During the surveillance period, data from 3153 patients was examined, (1797 (57.0%) men vs. 1356 (43.0%) females, and 1.2 years (Q1: 0.01 months – Q3: 15 years). Of the samples submitted, 1026 (35.5%) samples were positive for the presence of pathogens (663(64.6%) pathogens vs. 363 (35.4%)) potential contaminants. In decreasing frequency, the most common isolates were: Coagulase-negative Staphylococcus (CoNs), 189 (28.6%); Klebsiella spp., 120 (18.2%); Escherichia coli, 66 (10.0%); Citrobacter spp., 48 (7.3%); Staphylococcus aureus, 47(7.1%); Pseudomonas aeruginosa, 34 (5.1%); and Salmonella spp., 33(5.1). The relative prevalence of BSIs changed somewhat over time (p-value < 0.001) with the isolation of multiple isolates trending upward from 2018 and onwards. Additional findings included the likely presence of extended spectrum beta lactamase (ESBL), high frequency of methicillin resistant Staphylococcus aureus (MRSA) (37(80.4%) and high rate of resistance to gentamicin (363(62.5%) and fluoroquinolones. Furthermore, the multiple antimicrobial resistances (MAR) index was relatively high (mean = 0.55, SD: ±0.23) with wide species-level variation. In a related density cluster analysis, we demonstrated a time-dependent increase in the diversity of resistotypes.
Conclusion: This study highlights the considerable health burden of AMR/or MDR in BSIs in Eritrea. Additionally, it underscores the urgent need for enhanced laboratory capacity, surveillance, institutionalisation of antibiotic stewardship programs, and robust infection control programs in hospitals across the country. The need for multidisciplinary research was also highlighted.
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National trends in Azithromycin consumption during 2017-2023 in Kazakhstan: impact of the COVID-19 pandemic and the imperative for enhanced clinical guidelines.
Authors: Kassym L et al
Abstract
Antibiotic resistance (AMR) has reached critical levels globally, especially in developing economies like Kazakhstan, largely due to improper antibiotic use. The aim of this study was to examine seven years of azithromycin sales data in Kazakhstan to uncover consumption patterns during the COVID-19 pandemic and develop effective strategies to combat AMR. This study analyzes two data sets: one from a comprehensive review of documents regulating azithromycin use in Kazakhstan. The second data set consists of a pharmaco-epidemiological analysis of azithromycin consumption from procurement data provided by Vi-ORTIS. Azithromycin consumption (ATC group J01FA10) from 2017 to 2023 was measured in DDD/1000 inhabitants/day (DID) using the ATC/DDD methodology. Azithromycin is extensively used in adult and pediatric care in Kazakhstan. Its consumption, measured in DDD per 1,000 inhabitants, surged in 2020 with the COVID-19 outbreak. The steady annual increase in “Watch” antibiotics, including azithromycin, should alarm Kazakhstan’s healthcare system. This trend highlights the need for stronger stewardship programs, targeted interventions, and comprehensive monitoring to prevent antibiotic overuse and misuse. Addressing this is crucial to maintaining antibiotic effectiveness and safeguarding public health.
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QAAPT: an interoperable web-based open-source tool for antimicrobial resistance data analysis and visualisation.
Authors: Sujan MJ et al
Abstract
The analysis and visualisation of antimicrobial resistance (AMR) surveillance data is a crucial challenge, especially in high-burden, low-middle-income countries. The authors describe the design, development, integration, and implementation of the Quick Analysis of Antimicrobial Patterns and Trends (QAAPT) tool for AMR data analysis and visualisation. The QAAPT tool was created by the Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia project, led by the International Vaccine Institute (IVI). This open-source web-based tool/application generates statistical and visual outputs of AMR data, offers data curation options, and can be integrated with laboratory information management systems. The QAAPT tool is user-friendly and is operable by someone with limited expertise in software or programming. As a part of the project, the tool was used to analyse data from 72 laboratories across 7 Asian countries. In this study, the authors present the technical aspects of tool development and highlight implementation outcomes for analysing and generating visual reports from more than 2.37 million highly heterogeneous antimicrobial susceptibility test data points.
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An Unusual ‘Gift’ from Humans: Third-Generation Cephalosporin-Resistant Enterobacterales in migratory birds along the East Asian-Australasian Flyway.
Authors: Cheng Z et al
Abstract
Migratory birds play a pivotal role in the global dissemination of antimicrobial resistance genes (ARGs), with shorebirds relying on coastal wetlands during their long-distance migrations, environments often contaminated and conducive to ARG transmission. However, systematic investigations into antimicrobial resistance (AMR) in shorebirds remain scarce. During spring and autumn of 2023, the authors collected 893 throat and cloacal swabs from 480 shorebirds, representing 28 species, at Chongming Dongtan, a critical stopover along the East Asian-Australasian Flyway. The analysis identified six strains, including four extra-intestinal pathogenic E. coli (ExPEC) and two K. pneumoniae, that exhibited resistance to third-generation cephalosporins, with three ExPEC strains exhibiting significant virulence in Galleria mellonella infection assays. The authors identified two conjugative plasmids: E042113F_p1, carrying the blaCMY-2 gene in E. coli, and M50_p2, carrying the blaKPC-2 gene in a hypervirulent K. pneumoniae with a virulence plasmid harboring the aerobactin system. Bioinformatic and experimental analyses confirmed that these plasmids could transfer without any fitness cost, remaining stable for at least 30 passages. Surprisingly, genomic tracing revealed that among the plasmids similar to E042113F_p1 (blaCMY-2), the earliest was identified in a Chinese swallow in 2015, with subsequent detections in wild birds from Mongolia (2017), Russia (2018), and Australia (2019). Notably, these E04-CMY-like/M50-KPC-like plasmids predominantly originated from human sources, underscoring the pivotal role of human activity in the cross-species transmission of AMR. This human-mediated transmission of resistance elements into wildlife posed a substantial risk for amplifying and disseminating AMR through long-range migratory bird movements, highlighting the urgent need for international collaboration under a One Health framework. Integrated surveillance, environmental management, and stringent antibiotic stewardship are critical to mitigating the risks posed by migratory birds in amplifying and spreading AMR across ecosystems.
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Improving effective antimicrobial resistance (AMR) prevention in ambulatory care: lessons from secondary appraisal of Belgian anti-infectious treatment care guidelines.
Authors: Van Laethem J et al
Abstract
The emergence of antimicrobial resistance (AMR) has been designated as a global threat by the World Health Organization. To combat AMR in Belgium, the Belgian Antibiotic Policy Coordination Committee (BAPCOC) has, among others, developed guidelines for the appropriate use of antimicrobials in the ambulatory practice. The authors aim to assess the current guidelines from an antimicrobial stewardship perspective and procide suggestions for improving the ambulatory antibiotic guidelines for first-line healthcare providers. The 2022 BAPCOC guidelines were independently evaluated by 7 antimicrobial stewardship experts based on the five “Ds” of antimicrobial stewardship. The results were aggregated, summarized, and consensus was sought. Recommendations improving the guidelines were formulated. A total of 52 recommendations were made, covering 16 different (sub)chapters. The most frequently covered topics were urinary tract infections, followed by skin and soft tissue infections. Among the top five recommendations deemed to have the greatest impact on antimicrobial stewardship outcomes, three were related to the diagnosis or treatment duration of urinary tract infections. Tailoring infectious disease and antibiotic treatment guidelines to antimicrobial stewardship principles and the latest literature is essential in combating antimicrobial resistance. Implementing the proposed recommendations in the Belgian ambulatory treatment guidelines could significantly enhance rational and judicious antibiotic use while minimizing the risk of ‘antibiotic undertreatment. The proposed ‘Choosing Wisely’ recommendations have the potential to be applied to a broader (European) context.
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Factors associated with health seeking behaviours and practice of antibiotics self-medication among adults in Abakaliki Metropolis, Ebonyi State, Nigeria.
Authors: Adeke AS et al
Abstract
One of the inappropriate health seeking behaviours (HSBs) people express when they feel ill is self-medication (SM) with antibiotics. The consequence of SM with antibiotics is the increase in antimicrobial resistance (AMR). Therefore, this study aimed to assess HSBs and the practice of SM with antibiotics among adults in Abakaliki, Nigeria. The study was undertaken using community-based cross-sectional study design. Multi-stage sampling technique was used to select 448 study respondents. Data were collected with interviewer-administered questionnaire in May 2021 and analysed using SPSS version 26. Frequency tables were used to present the descriptive statistics. Bivariate and multivariate analyses of HSB and practice of SM with antibiotics against socio-demographic characteristics were done and statistically significant findings were considered with the alpha level of significance set at 5%. Only 161 (35.9%) of the respondents had appropriate HSB (consulting a doctor) as their first action when experiencing a health problem. Factors reported by majority of respondents to influence HSBs were perceived severity of illness 321 (71.7%), knowledge/past experience of illness 306 (68.3%), and cost of treatment 304 (67.9%). The predictors of HSB were being single (AOR = 0.349, 95%CI = 0.172-0.709), privately/self-employed (AOR = 0.337, 95%CI = 0.158-0.720), unemployed (AOR = 0.219, 95%CI = 0.074-0.645), living with family members (AOR = 0.549, 95%CI = 0.307-0.981), and earning ≥ 100,000 naira (AOR = 3.619, 95%CI = 1.271-10.303). Many respondents 431 (96.2%) had ever practiced antibiotics SM. Over half 252 (58.5%) had practiced antibiotics SM in the previous three months before the study. Factors reported to influence antibiotics SM were successful treatment from previous use of prescribed antibiotics 366 (84.9%), easy access to antibiotics from drug stores 357 (82.8%), knowledge/past experience of illness 326 (75.6%), and affordable cost of care in drug stores 325 (75.4%). The predictors of antibiotics SM were being single (AOR = 0.578, 95%CI = 0.351-0.953) and earning 30,000-49,999 naira (AOR = 0.463, 95%CI = 0.268-0.802). Most of the respondents had inappropriate HSBs and almost all had practiced antibiotics SM previously. There is need for mass sensitisations and enforcement of antibiotic dispensing laws in Nigeria. Also, scaling up health insurance in communities may address some identified factors influencing HSBs and SM, such as insufficient funds to visit a health facility.
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The effects of topical antimicrobial-corticosteroid combination therapy in comparison to topical steroids alone on the skin microbiome of patients with atopic dermatitis
Authors: Li Tingting
Abstract
Objective: This study aims to analyze the different therapeutic responses between topical antimicrobial-corticosteroid combination and topical corticosteroids alone on improving the skin microbiome and skin barrier of patients with atopic dermatitis (AD).
Methods: Forty patients with mild-to-moderate AD were randomly assigned to receive two kinds of treatment. Skin swabs were collected from the lesional sites and nearby nonlesional sites at baseline, after topical medication treatment and 2 weeks post-treatment, and were analyzed by DNA sequencing of the fungal internal transcribed spacer (ITS)1-5 rDNA gene and the V3V4 region of the bacterial 16S rRNA gene.
Results: According to our research analysis, both topical steroids alone and combination treatment of steroids and antimicrobials effectively improved the severity of AD and repaired skin barrier. AD lesions were characterized by a decreased sebum level, lower abundance of Cutibacterium and a higher abundance of Staphylococcus. A combined topical treatment with an antimicrobial and steroid showed better responses in increasing skin sebum level and restoring the skin bacterial microbiome, whereas topical steroid alone did not improve skin dysbiosis.
Conclusion: A combined therapy with antimicrobial and steroid helps to recover the skin microbiome. Further studies are necessary to explore the therapeutic effects of treatments aiming at balancing the microbiome.
Keywords: Atopic dermatitis; skin microbiome; therapeutic responses.
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Efficacy and safety of switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir/abacavir/lamivudine: Results from an open-label extension of a phase 3 randomized, double-blind, multicenter, active-controlled, non-inferiority study
DOI: 10.1097/MD.0000000000041482.
Authors: Indira Brar
Abstract
Background: The phase 3 randomized, active-controlled GS-US-380-1844 (NCT02603120) study evaluated switching to the single-tablet regimen bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) from dolutegravir (DTG), abacavir (ABC), and lamivudine (3TC) among people with HIV-1. Previously, results from the 48-week double-blind phase showed that switching to B/F/TAF was noninferior to remaining on DTG/ABC/3TC and that B/F/TAF was well tolerated. Here, we show the long-term safety and efficacy of switching to B/F/TAF from DTG/ABC/3TC among people with HIV-1.
Methods: Participants were virologically suppressed people with HIV-1 (HIV-1 RNA <50 copies/mL for ≥ 3 months prior to screening) receiving DTG/ABC/3TC at baseline. Participants were randomized 1:1 to switch to B/F/TAF or remain on DTG/ABC/3TC. Following 48 weeks of treatment with B/F/TAF or DTG/ABC/3TC in the double-blind phase, participants had the option to enter an open-label extension phase, during which they received B/F/TAF. Virologic, immunologic, and safety outcomes during treatment with B/F/TAF through the open-label extension up to 168 weeks, including preexisting and treatment-emergent resistance, were analyzed.
Results: Among 547 participants in the all-B/F/TAF analysis set, virologic suppression (HIV-1 RNA < 50 copies/mL) was maintained in 99% to 100% of participants up to 168 weeks into B/F/TAF treatment, including in those with preexisting resistance; no treatment-emergent resistance was detected. CD4 cell counts remained stable during B/F/TAF treatment, with median (interquartile range) changes from baseline of -17 (-120, 65) cells/µL at week 48 and -9 (-100, 108) cells/µL at week 96. Safety and tolerability findings were consistent with previously reported findings up to week 48; most drug-related adverse events were grade 1 or 2 in severity; no new safety signals were identified.
Conclusion: Switching to B/F/TAF from DTG/ABC/3TC was associated with continued high rates of virologic suppression up to week 168, with no treatment-emergent resistance. B/F/TAF was well tolerated throughout the study period.
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Acceptability of an annual tenofovir alafenamide implant for HIV prevention in South African women: findings from the CAPRISA 018 Phase I clinical trial
DOI: 10.1002/jia2.26426
Authors: Tanuja N Gengiah
Abstract
Introduction: Long-acting HIV pre-exposure prophylaxis promises to improve uptake, adherence and persistence challenges experienced with daily oral tablets. We assessed the acceptability of an annual tenofovir alafenamide (TAF) implant in South African women enrolled from 9 July 2020 until 31 May 2022 in a Phase I trial.
Methods: Six women received one TAF implant for 4 weeks (Group 1), after which 30 women were randomized (4:1, TAF to placebo ratio) to receive 1 or 2 TAF or placebo implants for 48 weeks (Group 2), before trial discontinuation. Acceptability assessments were conducted pre- and post-implant removal. Implant attributes (size, quantity, insertion site, palpability, visibility) and physical experiences (insertion/removal procedures, implant site reactions [ISRs]) were rated on a scale of 1 (highly unacceptable) to 6 (highly acceptable), with 4 being the acceptability threshold. The mean (range) of the mean acceptability scores across all pre-removal visits were calculated, including stratification by removal timing (early vs. scheduled). Implant likes and dislikes were also assessed.
Results: The median participant age was 26 years. Prior to implant removal, the mean (range) acceptability scores were 5.4 (3.6-6.0) for product attributes and 5.1 (1.7-6.0) for physical experiences. Eleven (31%) participants had early implant removals, occurring on average 19 weeks (range 2-27 weeks) after insertion. The proportion of study visits reporting adherence measure as unacceptable in early versus scheduled removals: ISRs (50% vs. 19%), visibility (30% vs. 15%), palpability (14% vs. 8%), pain (16% vs. 4%) and implant quantity (13% vs. 1%). Pre-removal acceptability scores for ISRs (p = 0.003) and physical experiences (p = 0.05) were significantly associated with early removal. Overall, mean (range) acceptability scores were 5.8 (4.0-6.0) and 5.9 (4.7-6.0) for lifestyle compatibility and likelihood of recommendation, respectively. After removal, 39% of participants found ISRs unacceptable, followed by 22% citing implant visibility. Potential for long-term HIV protection, followed by discreet and convenient use, were most liked, while ISRs were the most disliked aspect.
Conclusions: While implant attributes, physical experiences and insertion/removal procedures were largely acceptable, local ISRs significantly reduced tolerability and acceptability, resulting in higher-than-expected early removals. The potential benefits of an annual TAF implant may be undermined unless tolerability is improved.
Keywords: HIV prevention; PrEP; acceptability; clinical trial; implant; tenofovir alafenamide.
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The effect of perioperative probiotics and synbiotics on postoperative infections in patients undergoing major liver surgery: a meta-analysis of randomized controlled trials
DOI: 10.7717/peerj.18874
Authors: Haopeng Wu
Abstract
Objective: To evaluate the effect of perioperative probiotics or synbiotics on the incidence of postoperative infections following major liver surgery.
Design: Meta-analysis.
Data sources: PubMed, Embase, Scopus, and the Cochrane Library for relevant English-language studies published up to February 21st, 2024.
Eligibility criteria: Randomized controlled trials evaluating perioperative probiotics or synbiotics for preventing postoperative infections in patients undergoing major liver surgery.
Data extraction and synthesis: Outcomes included postoperative infection incidence, antibiotic therapy duration, length of stay in intensive care unit (ICU) and hospital. A random-effect model was adopted for the meta-analysis. The quality of included studies was evaluated using the Cochrane risk of bias tool.
Results: Ten studies involving 588 patients were included. Pooled analyses revealed that perioperative probiotics or synbiotics significantly reduced postoperative infection incidence (RR 0.36, 95% CI [0.24-0.54], P < 0.0001, I2 = 6%) and antibiotic therapy duration (MD -2.82, 95% CI [-3.13 to -2.51], P < 0.001, I2 = 0%). No significant differences were observed in length of stay in ICU (MD -0.25, 95% CI [-0.84-0.34], P = 0.41, I2 = 64%) or length of stay in hospital (MD -1.25, 95% CI [-2.74-0.25], P = 0.10, I2 = 56%).
Conclusions: This meta-analysis suggests that perioperative administration of probiotics or synbiotics may reduce the incidence of postoperative infections and duration of antibiotic therapy. Their use as adjunctive therapy during the perioperative period could be considered for patients undergoing major liver surgery.
Keywords: Liver surgery; Meta-analysis; Postoperative infections; Prebiotics; Probiotics.
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Efficacy and safety of vaginal suppositories containing combination of Natamycin and Lactulose in treatment of vulvovaginal candidiasis: international, randomized, controlled, superiority clinical trial (combination of Natamycin and Lactulose for treatment of vulvovaginal candidiasis)
Authors: Oksana N Volkova
Abstract
Background: The study aimed to assess the efficacy and safety of Natamycin + Lactulose vaginal suppositories (100 mg natamycin and 300 mg lactulose) (AVVA RUS JSC, Russia) in adult females with vulvovaginal candidiasis.
Methods and results: An international, randomized, controlled, assessor-blinded clinical trial enrolled 218 females randomly distributed into three groups: Natamycin + Lactulose (92 patients), Lactulose (36 patients), and Pimafucin® (90 patients). The study drug and comparator drugs had an identical dosing regimen (one suppository intravaginally once a day at bedtime for six days). The study involved four visits to the study site with examination at Visits 2 and 3. The fixed-dose combination of Natamycin + Lactulose was superior to both comparator drugs in terms of the primary efficacy endpoint defined as the percentage of patients achieving a clinical recovery: the absence of symptoms of vulvovaginal candidiasis. At Visit 2, clinical recovery was reported in 81.6% of females in the Natamycin + Lactulose group compared to 42.9% and 62.3% of patients in the Lactulose and Pimafucin groups, respectively. The difference in proportions was 38.8% and 18.4%. In the Natamycin + Lactulose group, microscopic recovery was observed in 75.9% of patients at Visit 2 and in 90.8% of patients at Visit 3. In the Lactulose group, 45.7% and 74.3% subjects responded positively at Visits 2 and 3. In Pimafucin group, microscopic recovery was reported in 71.3% and 88.5% of patients at Visits 2 and 3, respectively, while no differences were observed between the Natamycin + Lactulose and Pimafucin groups at both visits. At Visit 3, the number of vaginal lactobacilli was significantly higher in the Natamycin + Lactulose group. In females with the low baseline content of vaginal lactobacilli, the combination drug under investigation increased the vaginal lactobacilli content to the reference values in 15.4% and 20.9% of patients at Visit 2 and Visit 3, respectively.
Conclusions: The fixed-dose combination Natamycin + Lactulose 100 mg + 300 mg vaginal suppositories (AVVA RUS JSC, Russia) demonstrated superior efficacy compared to 1) Pimafucin 100 mg and 2) Lactulose 300 mg vaginal suppositories in adult females with vulvovaginal candidiasis.
Trial registration: NCT06411314, retrospectively registered on May, the 13th, 2024.
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Guideline-based bismuth quadruple therapy for helicobacter pylori infection in China: A systematic review and network meta-analysis
Authors: Jiali Wei
Abstract
Background: Currently, quadruple therapy is unanimously recommended as the current first-line treatment option for Helicobacter pylori (H. Pylori) eradication. However, the drug composition of quadruple therapy is very complex, and the efficacy and safety between them is not clear.
Aims: To compare the efficacy and safety of H. Pylori eradication regimens, which were recommended by the Fifth Consensus of China, by network meta-analysis.
Methods: Literature databases were used to retrieve clinical randomized controlled trials of H. Pylori eradication. Network meta-analysis was performed using BUGSnet and meta package of R software, using OR values as effect size, and SUCRA was used to rank the efficacy of interventions under each outcome.
Results: A total of 55 studies and 130 arms were included. The NMA analysis found that the top regimen in term of eradication rate outcome was: Rabeprazole + Bismuth + Furazolidone + Tetracycline (SUCRA, 97.5). In terms of safety outcomes: Lansoprazole + Bismuth + Amoxycillin + Clarithromycin (SUCRA, 91.97).
Conclusions: The bismuth quadruple therapies recommended by the guidelines for the treatment of H. Pylori have good performance in terms of four-week eradication rate and safety outcome indicators, and due to the different resistance of antibiotics in different regional populations, rational use of drugs should be combined with local conditions.
Copyright: © 2025 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Safety and efficacy of a defined bacterial consortium, VE303, to treat HE
Authors: Patricia P Bloom
Abstract
Background: Novel therapies are needed to treat HE, and microbiome modulation is a promising target. VE303 is a defined consortium of 8 purified, clonal bacterial strains, known to produce metabolites that may be beneficial in HE. We evaluated the safety and efficacy of VE303 to treat HE.
Methods: We performed a single-center, randomized, placebo-controlled trial of VE303 in adult patients with a history of overt HE (NCT04899115). Eligible patients were taking lactulose and rifaximin, had no recent systemic antibiotics, and had MELD ≤20. All patients received 5 days of oral vancomycin followed by randomization to 14 days of VE303 or placebo (2:1). The primary endpoints were incidence of serious adverse events and change in psychometric HE score (PHES) from baseline to 4 weeks after treatment. Stool samples underwent metagenomic sequencing and metabolite quantification.
Results: Eighteen patients completed the trial, 56% men, with a mean age of 59 years and a mean MELD of 11. Patients who received VE303 had a mean change in PHES of +1.5 versus -1.0 in those who received a placebo (p=0.20). Two of the 12 patients who received VE303 had at least 1 serious adverse event (all overt HE hospitalizations), compared with 0/6 patients who received a placebo. In the patients who received VE303, 2 of 8 strains engrafted in >50% of patients. Both VE303 strain engraftment and increased stool butyrate production had a trend toward improved PHES.
Conclusions: VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES.
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Audit and Feedback Interventions for Antibiotic Prescribing in Primary Care: A Systematic Review and Meta-analysis
DOI: 10.1093/cid/ciae604
Authors: Alice X T Xu
Abstract
Background: This systematic review evaluates the effect of audit and feedback (A&F) interventions targeting antibiotic prescribing in primary care and examines factors that may explain the variation in effectiveness.
Methods: Randomized controlled trials (RCTs) involving A&F interventions targeting antibiotic prescribing in primary care were included in the systematic review. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and ClinicalTrials.gov were searched up to May 2024. Trial, participant, and intervention characteristics were extracted independently by 2 researchers. Random effects meta-analyses of trials that compared interventions with and without A&F were conducted for 4 outcomes: (1) total antibiotic prescribing volume; (2) unnecessary antibiotic initiation; (3) excessive prescription duration, and (4) broad-spectrum antibiotic selection. A stratified analysis was also performed based on study characteristics and A&F intervention design features for total antibiotic volume.
Results: A total of 56 RCTs fit the eligibility criteria and were included in the meta-analysis. A&F was associated with an 11% relative reduction in antibiotic prescribing volume (N = 21 studies, rate ratio [RR] = 0.89; 95% confidence interval [CI]: .84, .95; I2 = 97); 23% relative reduction in unnecessary antibiotic initiation (N = 16 studies, RR = 0.77; 95% CI: .68, .87; I2 = 72); 13% relative reduction in prolonged duration of antibiotic course (N = 4 studies, RR = 0.87 95% CI: .81, .94; I2 = 86); and 17% relative reduction in broad-spectrum antibiotic selection (N = 17 studies, RR = 0.83 95% CI: .75, .93; I2 = 96).
Conclusions: A&F interventions reduce antibiotic prescribing in primary care. However, heterogeneity was substantial, outcome definitions were not standardized across the trials, and intervention fidelity was not consistently assessed. Clinical Trials Registration. Prospero (CRD42022298297).