What are the most effective community-based antimicrobial stewardship interventions in low- and middle-income countries? A narrative review.

Antimicrobial resistance (AMR) is a major global issue and antimicrobial stewardship is central to tackling its emergence. The burden of AMR disproportionately impacts low- and middle-income countries (LMICs), where capacity for surveillance and management of resistant pathogens is least developed. Poorly regulated antibiotic consumption in the community is a major driver of AMR, especially in LMICs, yet community-based interventions are neglected in stewardship research, which is often undertaken in high-income settings and/or in hospitals. We reviewed the evidence available to researchers and policymakers testing or implementing community-based antimicrobial stewardship strategies in LMICs. We critically appraise that evidence, deliver recommendations and identify outstanding areas of research need. We find that multifaceted, education-focused interventions are likely most effective in our setting. We also confirm that the quality and quantity of community-based stewardship intervention research is limited, with research on microbiological, clinical and economic sustainability most urgently needed.

Vision-based markerless registration using stereo vision and an augmented reality surgical navigation system: a pilot study.

BACKGROUND: This study evaluated the use of an augmented reality navigation system that provides a markerless registration system using stereo vision in oral and maxillofacial surgery. METHOD: A feasibility study was performed on a subject, wherein a stereo camera was used for tracking and markerless registration. The computed tomography data obtained from the volunteer was used to create an integral videography image and a 3-dimensional rapid prototype model of the jaw. The overlay of the subject's anatomic site and its 3D-IV image were displayed in real space using a 3D-AR display. Extraction of characteristic points and teeth matching were done using parallax images from two stereo cameras for patient-image registration. RESULTS: Accurate registration of the volunteer's anatomy with IV stereoscopic images via image matching was done using the fully automated markerless system, which recognized the incisal edges of the teeth and captured information pertaining to their position with an average target registration error of < 1 mm. These 3D-CT images were then displayed in real space with high accuracy using AR. Even when the viewing position was changed, the 3D images could be observed as if they were floating in real space without using special glasses. CONCLUSION: Teeth were successfully used for registration via 3D image (contour) matching. This system, without using references or fiducial markers, displayed 3D-CT images in real space with high accuracy. The system provided real-time markerless registration and 3D image matching via stereo vision, which, combined with AR, could have significant clinical applications.

Determinants of antibiotic prescribing in primary care in Vietnam: a qualitative study using the Theoretical Domains Framework.

BACKGROUND: To formulate effective strategies for antimicrobial stewardship (AMS) in primary care, it is crucial to gain a thorough understanding of factors influencing prescribers' behavior within the context. This qualitative study utilizes the Theoretical Domains Framework (TDF) to uncover these influential factors. METHODS: We conducted a qualitative study using in-depth interviews and focus group discussions with primary care workers in two provinces in rural Vietnam. Data analysis employed a combined inductive and deductive approach, with the deductive aspect grounded in the TDF. RESULTS: Thirty-eight doctors, doctor associates, and pharmacists participated in twenty-two interviews and two focus group discussions. We identified sixteen themes, directly mapping onto seven TDF domains: knowledge, skills, behavioral regulation, environmental context and resources, social influences, social/professional role and identity, and optimism. Factors driving unnecessary prescription of antibiotics include low awareness of antimicrobial resistance (AMR), diagnostic uncertainty, prescription-based reimbursement policy, inadequate medication supplies, insufficient financing, patients' perception of health insurance medication as an entitlement, and maintaining doctor-patient relationships. Potential factors facilitating AMS activities include time availability for in-person patient consultation, experience in health communication, and willingness to take action against AMR. CONCLUSION: Utilizing the TDF to systematically analyze and present behavioral determinants offers a structured foundation for designing impactful AMS interventions in primary care. The findings underscore the importance of not only enhancing knowledge and skills but also implementing environmental restructuring, regulation, and enablement measures to effectively tackle unnecessary antibiotic prescribing in this context.

A Novel Screening Method for Scoliosis Using a Bodysuit and 3-Dimensional Imaging.

STUDY DESIGN: A single-center prospective observational study. OBJECTIVE: To clarify the usefulness of a novel scoliosis screening method using a 3-dimensional (3D) human fitting application and a specific bodysuit. SUMMARY OF BACKGROUND DATA: Several scoliosis screening methods, such as scoliometer and Moiré topography, are available for detecting scoliosis. In the present study, a novel screening method for scoliosis using a 3D human fitting application and a specific bodysuit was developed. PATIENTS AND METHODS: Patients with scoliosis or suspected scoliosis, patients with non-scoliosis, and healthy volunteers were enrolled. They were divided into "non-scoliosis" and "scoliosis" groups. The scoliosis group was further subdivided into "mild," "moderate," and "severe-scoliosis" groups. Patients' characteristics and Z values, which were calculated by a 3D virtual human body model created by a 3D human fitting application and a specific bodysuit to evaluate trunk asymmetry caused by scoliosis, were compared between the non-scoliosis and scoliosis groups or among the non, mild, moderate and severe-scoliosis groups. Finally, the optimal cutoff of the Z value was determined to detect moderate to severe scoliosis using receiver operating characteristic curve analysis. RESULTS: A total of 101 patients were included. The non-scoliosis group consisted of 47 patients, and the scoliosis group included 54 patients, with 11, 31, and 12 patients in the mild, moderate, and severe-scoliosis groups, respectively. The scoliosis group showed a significantly higher Z value than the non-scoliosis group. The moderate or severe-scoliosis group had a significantly higher Z value than the non or mild-scoliosis group. The receiver operating characteristic curve analysis revealed that the optimal cutoff of the Z value was 19.9 mm (sensitivity, 95.3% and specificity, 58.6%). CONCLUSION: A novel scoliosis screening method consisting of a 3D human fitting application and a specific bodysuit may be useful for detecting moderate to severe scoliosis.

Genomic epidemiological analysis of mcr-1-harboring Escherichia coli collected from livestock settings in Vietnam.

Livestock has been implicated as a reservoir for antimicrobial resistance (AMR) genes that can spread to humans when antimicrobials are used in animals for food production to treat clinical diseases and prevent and control common disease events. In Vietnam, mcr-1-harboring Escherichia coli (MCRPEC) strains have been isolated from humans, animals (chickens, pigs, and dogs) feces, flies, foods, and the environment (rainwater, well water, and irrigation water) in communities and from clinical specimens in hospitals. The relationship between levels of AMR in livestock and its occurrence in humans is complex and is driven by many factors. We conducted whole genome sequencing of MCRPEC to analyze the molecular epidemiological characteristics, history, and relatedness of 50 isolates obtained in 2019 from different reservoirs in farms and markets in Ha Nam province, Vietnam. 34 sequence types (STs) with 3 new STs were identified in multilocus sequence typing analysis: ST12945 and ST12946 from chicken feces, and ST12947 from flies. The AMR phenotypes of 50 MCRPEC isolates were as follows: ampicillin (100%, 50/50), cefotaxime (10%, 5/50), gentamicin (60%, 30/50), amikacin (8%, 4/50), meropenem (6%, 3/50), ceftazidime (18%, 9/50), colistin (24%, 12/50) and ciprofloxacin (80%, 40/50). All 50 MCRPEC isolates were identified as MDR. 100% (50/50) isolates carried AMR genes, ranging from 5 to 22 genes. The most prevalent plasmid replicon types carrying mcr-1 were IncP-1 (17/37, 45.9%), IncX4 (7/37, 18.9%), and IncHI2/IncHI2A (6/37, 16.2%). These data suggest that the epidemiology of the mcr-1 gene is mostly determined by plasmid spreading instead of clonal dissemination of MCRPE strains. The co-occurrence of several STs such as ST10, ST48, ST155, ST206, ST2705 in various sample types, joined to the higher prevalence of a few types of Inc plasmids, confirms the dissemination of the mcr-1 carrying plasmids in E. coli clones established in livestock. 5 over 8 STs identified in flies (ST206, ST2705, ST155, ST10, and ST48) suggested the fly contribution in the transmission of AMR bacteria in environments. These popular STs also occur in human samples and 100% of the human samples were positive for the mcr-1 gene.

Carriage of Plasmid-Mediated Colistin Resistance-1-Positive Escherichia coli in Humans, Animals, and Environment on Farms in Vietnam.

Plasmid-Mediated Colistin Resistance 1 (mcr-1) was first reported in 2015 and is a great concern to human health. In this study, we investigated the prevalence of mcr-1 and mcr-1-positive Escherichia coli (MCRPEC) and the association in infection status among various reservoirs connected to livestock. The study was conducted in 70 poultry and swine farms in a commune in Ha Nam province, northern Vietnam. Samples were collected from farmers, food animals, domestic animals, and farm environments (flies and wastewater) for polymerase chain reaction (PCR) screening for mcr-1 gene and species identification of PCR positive isolates. Among 379 obtained mcr-1 positives isolates, Escherichia coli was the major identified, varying from 50% (2/4) in dog feces to 100% (31/31) in humans feces isolates. The prevalence of MCRPEC was 14.4% (20/139), 49.7% (96/193), 31.3% (25/80), 36.7% (40/109), 26.9% (18/67), and 3.9% (2/51) in humans, chickens, pigs, flies, wastewater, and dogs, respectively. The study identified association between MCRPEC infection status in humans and flies (OR = 3.4), between flies and chickens (OR = 5.3), and between flies and pigs (OR = 9.0). Farmers' age and farm livestock unit were also associated factors of MCRPEC infection status in humans (OR = 5.1 and 1.05, respectively). These findings bring new knowledge on antibiotic resistance in livestock setting and important suggestions on potential role of flies in the transmission of mcr-1 resistance gene.

Characterization of Genetic Elements Carrying mcr-1 Gene in Escherichia coli from the Community and Hospital Settings in Vietnam.

Colistin is widely used in agriculture and aquaculture as prophylaxis, particularly in Asia. Recently, mcr-1 and other mobilizable genes conferring colistin resistance have spread globally in community and hospital populations. Characterizing mcr-1 mobile genetic elements and host genetic background is important to understand the transmission of this resistance mechanism. We conducted whole-genome sequencing of 94 mcr-1-positive Escherichia coli isolates (Mcr1-Ec isolates) from human and animal feces, food, and water in a community cohort (N = 87) and from clinical specimens from a referral hospital (N = 7) in northern Vietnam. mcr-1 was plasmid-borne in 71 and chromosomally carried in 25 (2 isolates contain one copy on chromosome and one copy on a plasmid) of 94 E. coli isolates from the community and hospital settings. All seven clinical isolates carried mcr-1 on plasmids. Replicon types of mcr-1-carrying plasmids included IncI2, IncP, IncX4, and IncFIA single replicons and combinations of IncHI2, IncN, and IncX1 multireplicons. Alignment of a long-read sequence of an IncI2 plasmid from animal feces with short-read sequences of IncI2 plasmids from a healthy human, water, and hospitalized patients showed highly similar structures (query cover from 90% to 98%, overall identity of >81%). We detected the potential existence of multireplicon plasmids harboring mcr-1 regardless of sample setting, confirming 10/71 with long-read sequencing. An intact/conserved Tn6330 transposon sequence or its genetic context variants were found in 6/25 Mcr1-Ec isolates with chromosomally carried mcr-1. The dissemination of mcr-1 is facilitated by a high diversity of plasmid replicon types and a high prevalence of the chromosomal Tn6330 transposon. IMPORTANCE The article presented advances our understanding of genetic elements carrying mcr-1 in Escherichia coli in both community and hospital settings. We provide evidence to suggest that diverse plasmid types, including multireplicon plasmids, have facilitated the successful transmission of mcr-1 in different reservoirs. The widespread use of colistin in agriculture, where a high diversity of bacteria are exposed, has allowed the selection and evolution of various transmission mechanisms that will make it a challenge to get rid of. Colocalization of mcr-1 and other antibiotic resistance genes (ARGs) on multireplicon plasmids adds another layer of complexity to the rapid dissemination of mcr-1 genes among community and hospital bacterial populations and to the slow pandemic of antimicrobial resistance (AMR) in general.

Analysis of Antimicrobial Resistance in Non-typhoidal Salmonella Collected From Pork Retail Outlets and Slaughterhouses in Vietnam Using Whole Genome Sequencing.

Non-typhoidal salmonella (TS) remains a significant health burden worldwide. In Vietnam, pork accounts for 70% of the total meat consumed, and contamination with Salmonella is high. High levels of antimicrobial resistance (AMR) have emerged among porcine NTS and of particular concern is the emergence of colistin resistance, a "last defense" antibioic against multi-drug resistant (MDR) Gram-negative pathogens. This study aimed to investigate the antibiotic susceptibility of 69 NTS isolates collected from the pork retail outlets and slaughterhouses in Vietnam during 2014 a nd 2018/19. Phenotypic testing and whole genome sequencing was used to assess the serotype and AMR gene profiles of the 69 NTS isolates. Seventeen different serotypes were identified, of which S. enterica subsp enterica serotype Typhimurium was the most common followed by S. ser. Rissen, S. ser. London, S. ser. Anatum, and S. ser. Derby. Phenotype AMR was common with 41 (59.4%) isolates deemed MDR. MDR strains were most common in slaughterhouses (83%) and supermarkets (75%) and lowest in traditional markets (38%) and convenience stores (40%). Colistin resistance was identified in 18 strains (15 resistant, three intermediate) with mcr-1 identified in seven isolates (S. ser. Meleagridis, S. Rissen, S. Derby) and mcr-3 in two isolates (S. Typhimurium). This includes the first mcr positive S. Meleagridis to our knowledge. Surprisingly, boutique stores had high levels (60%) of MDR isolates including 5/20 isolates with mcr-1. This study demonstrates that pork from modern retail stores classed as supermarkets or boutique (with pork claiming to be high quality, traceable, environmentally friendly marketed toward higher income consumers) still contained NTS with high levels of AMR.

Cross-Sectional Analysis of the Microbiota of Human Gut and Its Direct Environment in a Household Cohort with High Background of Antibiotic Use.

Comprehensive insight into the microbiota of the gut of humans and animals, as well as their living environment, in communities with a high background of antibiotic use and antibiotic resistance genes is scarce. Here, we used 16S rRNA gene sequencing to describe the (dis)similarities in the microbiota of feces from humans (n = 107), domestic animals (n = 36), water (n = 89), and processed food (n = 74) in a cohort with individual history of antibiotic use in northern Vietnam. A significantly lower microbial diversity was observed among individuals who used antibiotics in the past 4 months (n = 44) compared to those who did not (n = 63). Fecal microbiota of humans was more diverse than nonhuman samples and shared a small part of its amplicon sequence variants (ASVs) with feces from animals (7.4% (3.2-9.9)), water (2.2% (1.2-2.8)), and food (3.1% (1.5-3.1)). Sharing of ASVs between humans and companion animals was not associated with the household. However, we did observe a correlation between an Enterobacteriaceae ASV and the presence of extended-spectrum beta-lactamase CTX-M-group-2 encoding genes in feces from humans and animals (p = 1.6 × 10-3 and p = 2.6 × 10-2, respectively), hinting toward an exchange of antimicrobial-resistant strains between reservoirs.

Resistance mechanisms and genetic relatedness among carbapenem-resistant Pseudomonas aeruginosa isolates from three major hospitals in Hanoi, Vietnam (2011-15).

BACKGROUND: MDR bacteria including carbapenem-resistant Pseudomonas aeruginosa are recognized as an important cause of hospital-acquired infections worldwide. This investigation seeks to determine the molecular characterization and antibiotic resistance genes associated with carbapenem-resistant P. aeruginosa. METHODS: We conducted WGS and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from August 2011 to March 2015 in three major hospitals in Hanoi, Vietnam. RESULTS: We identified three variants of IMP gene, among which bla IMP-15 was the most frequent (n = 34) in comparison to bla IMP-26 (n = 2) and bla IMP-51 (n = 12). We observed two isolates with imipenem MIC >128 mg/L that co-harboured bla IMP-15 and bla DIM-1 genes and seven isolates (imipenem MIC > 128 mg/L) with a bla KPC-1 gene from the same hospital. MLST data shows that these 72 isolates belong to 18 STs and phylogenetic tree analysis has divided these isolates into nine groups. CONCLUSIONS: Our results provide evidence that not only bla IMP-26 but other IMP variants such as bla IMP-15 and bla IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminating in healthcare settings in Vietnam. In addition, we report the emergence of two isolates belonging to ST1240 and ST3340 that harboured two important carbapenemase genes (bla IMP-15 and bla DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa that carried the bla KPC-1 gene in Vietnam, which could potentially cause serious restricted availability of treatment options in healthcare settings.

Filamentous vibriophage fs2 encoding the rstC gene integrates into the same chromosomal region as the CTX phage [corrected].

The genome of the filamentous phage of Vibrio cholerae fs2 was found to contain rstC and rstB1 (truncated) genes downstream of ORF500. att-fs2-dir and att-fs2-rev sequences homologous to that of att-CTXphi were found between orf500 and rstC of the fs2 genome. This prompted us to search for the integration site of fs2 in the genomes of V. cholerae O1 and O139. The genome of fs2 was found to integrate downstream of attRS of the CTXphi phage, which integrated into chromosome I of V. cholerae O1 and O139. When infected with fs2, a fimbriate strain of V. cholerae O1 appeared to reduce fimbrial production in an adult rabbit ileal loop assay.

Characterization of Vibrio cholerae O139 of an Aquatic Isolate in Northern Vietnam.

During the cholera survey in Namdinh province (northern Vietnam) in July, 2010, one strain of Vibrio cholerae O139 was isolated from 7 environmental water samples positive for ctxA, toxR,VCO139 genes and named as V. cholerae O139, ND1 strain. This strain was lysogenic harbouring a genome similar to the filamentous phage fs1. The replicative form DNA of this phage (named as ND1-fs1, 6856 bp) was sequenced and compared with the other filamentous phages. The filamentous phage ND1-fs1 integrates into the region between ctxB and rtxA genes. The genetic organization of the CTXϕ of V. cholerae O139, strain ND1 was determined and the schematic representation of the genetic organization was shown together with the ND1-fs1 prophage.

Augmented reality system for oral surgery using 3D auto stereoscopic visualization.

We present an augmented reality system for oral and maxillofacial surgery in this paper. Instead of being displayed on a separated screen, three-dimensional (3D) virtual presentations of osseous structures and soft tissues are projected onto the patient's body, providing surgeons with exact knowledge of depth information of high risk tissues inside the bone. We employ a 3D integral imaging technique which produce motion parallax in both horizontal and vertical direction over a wide viewing area in this study. In addition, surgeons are able to check the progress of the operation in real-time through an intuitive 3D based interface which is content-rich, hardware accelerated. These features prevent surgeons from penetrating into high risk areas and thus help improve the quality of the operation. Operational tasks such as hole drilling, screw fixation were performed using our system and showed an overall positional error of less than 1 mm. Feasibility of our system was also verified with a human volunteer experiment.

Precision-guided surgical navigation system using laser guidance and 3D autostereoscopic image overlay.

This paper describes a precision-guided surgical navigation system for minimally invasive surgery. The system combines a laser guidance technique with a three-dimensional (3D) autostereoscopic image overlay technique. Images of surgical anatomic structures superimposed onto the patient are created by employing an animated imaging method called integral videography (IV), which can display geometrically accurate 3D autostereoscopic images and reproduce motion parallax without the need for special viewing or tracking devices. To improve the placement accuracy of surgical instruments, we integrated an image overlay system with a laser guidance system for alignment of the surgical instrument and better visualization of patient's internal structure. We fabricated a laser guidance device and mounted it on an IV image overlay device. Experimental evaluations showed that the system could guide a linear surgical instrument toward a target with an average error of 2.48 mm and standard deviation of 1.76 mm. Further improvement to the design of the laser guidance device and the patient-image registration procedure of the IV image overlay will make this system practical; its use would increase surgical accuracy and reduce invasiveness.

Two different mechanisms of ampicillin resistance operating in strains of Vibrio cholerae O1 independent of resistance genes.

Autoagglutinable strains of Vibrio cholerae O1 (seven nonfimbriate strains and one fimbriate strain) were transformed to obtain resistance to ampicillin. Two distinct mechanisms were found in these strains. One was operating in nonfimbriate strains by reducing OmpU protein production and the other was operating in a fimbriate strain (Bgd17) by newly overproducing cpxP protein. The twitching motility in the fimbriate Bgd17 strain disappeared depending on the production of cpxP protein, suggesting that fimbriation of V. cholerae O1 is controlled by a two-component signal transduction system.