Antimicrobial-resistant Infections Research Articles

Complex Foot Infection Treated With Surgical Debridement and Antibiotic Loaded Calcium Sulfate—A Retrospective Cohort Study of 137 Cases

Complex foot infections involving bone and soft tissue in patients with co-morbidities such as diabetes and peripheral arterial disease (PAD) are a cause of significant hospital admission. They are associated with substantial economic costs to health services worldwide. Historically, severe foot infection has been treated with surgical debridement and prolonged courses of systemic antibiotics. Prolonged systemic antibiotic use increases the risk of drug side effects, antimicrobial resistance and Clostridium difficile infection. The purpose of this study was to investigate whether surgical debridement and implantation of antibiotic loaded calcium sulfate is effective in the resolution of foot infection and wound healing. A retrospective cohort study of 137 consecutive cases of osteomyelitis (127) or significant soft tissue infection (10) over 62 months from 02/2013 to 04/2018 was conducted following local ethical approval. All cases of infection were treated with surgical debridement and local antibiotic-loaded calcium sulfate. The primary outcomes of infection resolution, time to healing and duration of postoperative antibiotics were measured. In 137 cases, 88.3% of infections resolved. Infection was eradicated in 22 patients without postoperative systemic antibiotics. About 82.5% of wounds healed, with an average healing time of 11.3 weeks. Healing time was significantly increased for the co-morbidities of diabetes and PAD (p =< .05) and for those requiring prolonged systemic postoperative antibiotics. Conservative surgical debridement and implantation of local antibiotic impregnated calcium sulfate is safe and effective in managing complex foot infections. We advocate early surgical intervention before deeper tissue involvement to help preserve lower limb structure and function.

Experiences of veterans with spinal cord injury related to annual urine screening and antibiotic use for urinary tract infections.

Antimicrobial-resistant bacterial infections are an increasing public health threat and people with spinal cord injury (SCI) are disproportionally at higher risk. National guidelines concerning urine testing after SCI are conflicting. Unnecessary urine testing in the SCI population (with high asymptomatic bacteriuria prevalence) leads to unnecessary antimicrobial use, propagating resistant infections, especially urinary tract infections (UTIs). (a) Describe UTI antimicrobial adherence in patients with SCI. (b) Explore SCI patient knowledge and attitudes toward current urine testing and treatment practices. Mixed methods. Veterans Health Administration (VHA) patients with SCI. Veterans identified as having SCI seen at a VHA facility nationwide. N/A. Self-reported medication adherence, patient beliefs and behaviors toward UTIs and antimicrobial use. A total of 105 Morisky Medication Adherence Scale-8 (MMAS-8) surveys were completed out of 369 distributed surveys (28% response rate). Overall, patients reported high medication adherence (mean score of 7.2/8, with 8 being a perfect adherence score). Ten qualitative interviews were completed. Themes identified include generally high adherence to prescribed antimicrobial courses and high levels of patient satisfaction with current outpatient VHA SCI bladder care. The quantitative findings converge with these themes observed in the qualitative interviews; patients were satisfied with current urine testing and treatment practices. Veterans with SCI are generally satisfied with their current UTI management and self-report taking antimicrobials for UTIs as prescribed. Veterans with SCI typically report high trust in their SCI providers and value their advice on bladder care management. Therefore, it is imperative for clinicians to provide evidence-based education to patients, as well as ensure that each prescribed course of antibiotics for UTI is clinically necessary. Information from this study will guide an intervention promoting appropriate urine testing and antimicrobial prescription practices by SCI providers.

Tackling Antimicrobial Resistance in the Shadow of COVID-19.

ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic is a challenge for ongoing efforts to combat antimicrobial-resistant (AMR) bacterial infections. As we learn more about COVID-19 disease and drug stewardship evolves, there is likely to be a lasting impact of increased use of antimicrobial agents and antibiotics, as well as a lack of consistent access to health care across many populations. Sexually transmitted infections have been underreported during the pandemic and are often caused by some of the most drug-resistant pathogens. In their recent article in mBio, Parzych et al. (E. M. Parzych, S. Gulati, B. Zheng, M. A. Bah, et al., mBio 12:e00242-21, 2021, https://doi.org/10.1128/mBio.00242-21) focus on protection against Neisseria gonorrhoeae infection via in vivo delivery of an antigonococcal DNA-encoded antibody that has been modified for increased complement activation. Nucleic acid approaches are highly adaptable and could be tremendously beneficial for personalized strategies to combat AMR pathogens.

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients

BackgroundThird-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts.MethodsWe performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU. Bacteria were isolated from rectal swabs (n = 287 and n = 103 patients ≤2 and > 2 days from admission, respectively) and diagnostic clinical specimens between Dec 2013 and March 2014. Isolates were subjected to Illumina whole-genome sequencing (n = 127 3GCR-GN, n = 41 VRE). Multi-locus sequence types (STs) and antimicrobial resistance determinants were identified from de novo assemblies. Twenty-three isolates were selected for sequencing on the Oxford Nanopore MinION device to generate completed reference genomes (one for each ST isolated from ≥2 patients). Single nucleotide variants (SNVs) were identified by read mapping and variant calling against these references.ResultsAmong 287 patients screened on admission, 17.4 and 8.4% were colonised by 3GCR-GN and VRE, respectively. Escherichia coli was the most common species (n = 36 episodes, 58.1%) and the most common cause of 3GCR-GN infection. Only two VRE infections were identified. The rate of infection among patients colonised with E. coli was low, but higher than those who were not colonised on admission (n = 2/33, 6% vs n = 4/254, 2%, respectively, p = 0.3). While few patients were colonised with 3GCR- Klebsiella pneumoniae or Pseudomonas aeruginosa on admission (n = 4), all such patients developed infections with the colonising strain. Genomic analyses revealed 10 putative nosocomial transmission clusters (≤20 SNVs for 3GCR-GN, ≤3 SNVs for VRE): four VRE, six 3GCR-GN, with epidemiologically linked clusters accounting for 21 and 6% of episodes, respectively (OR 4.3, p = 0.02).Conclusions3GCR-E. coli and VRE were the most common gut colonisers. E. coli was the most common cause of 3GCR-GN infection, but other 3GCR-GN species showed greater risk for infection in colonised patients. Larger studies are warranted to elucidate the relative risks of different colonisers and guide the use of screening in ICU infection control.

A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex

Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella, highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes.

Prevalence of Antimicrobial-Resistant Infection Among Patients Attending Assam Medical College and Hospital, Dibrugarh

Background: The burden of antimicrobial resistance (AMR) is increasing globally at an alarming rate, especially among hospitalized cases. However, there is still lack of knowledge about morbidity and mortality due to AMR infections among different populations. The present study was aimed to provide a brief insight on the prevalence of AMR infection among the patients attending Assam Medical College and Hospital, Dibrugarh, Assam, India. Materials and Methods: A retrospective cross-sectional study was conducted among the patients admitted in the hospital from April 2018 to April 2019. Blood culture reports of AMR-positive cases were collected from the Microbiology Department and hospitalization records including clinical and demographic data were retrieved from the Medical Records Department. Results: Overall, 251 blood culture reports positive for AMR infection were obtained during the study period. Of this, 96 cases (38.25%, 96/251) were females and 155 (61.75%, 155/251) were males. AMR infection was mostly prevalent among younger age group (0–1 month) with 85.65% (215/251). Methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumonia were the most frequently identified AMR pathogens in the study population with 31.47% (79/251), 23.90% (60/251), and 17.93% (45/251), respectively. Conclusion: The identified AMR pathogens were mostly prevalent among young infants and characterized with multidrug resistance. However, the extended study in increased population mostly among hospitalized cases may provide insights for understanding the burden of AMR and associated risk factors.

Antimicrobial Stewardship in Acute-Care Hospitals: A Report of the California Healthcare-Associated Infections Honor Roll

Background: Antimicrobial stewardship has been demonstrated to improve patient outcomes and reduce unwanted consequences, such as antimicrobial resistance and Clostridioides difficile infection. The California Department of Public Health (CDPH) Healthcare-Associated Infection (HAI) Program developed an honor roll to recognize facilities with the goal of promoting antimicrobial stewardship programs and encouraging collaboration and research. Methods: The first open enrollment period in California was from August 1 to September 1, 2020, and was only open to acute-care hospitals (ACHs). Enrollment occurs every 6 months. Applicants completed an application and provided supporting documentation for bronze, silver, or gold designations. The criteria for the bronze designation were at least 1 item from each of CDC’s 7 core elements for ACHs. The criteria for silver were bronze criteria plus 9 HAI program prioritized items (based on published literature) from the CDC Core Elements and demonstration of outcomes from an intervention. The criteria for gold designation were silver criteria plus community engagement (ie, local work or collaboration with healthcare partners). Applications were evaluated in 3 phases: (1) CDPH reviewed core elements and documentation, (2) CDPH and external blinded antimicrobial stewardship experts reviewed outcomes as scientific abstracts, and (3) CDPH reviewed each program for overall effectiveness in antimicrobial stewardship and final designation determination. Designations expire after 2 years. Results: In total, 119 applications were submitted (30% of all ACHs in California), of which 100 were complete and thus were included for review. Moverover, 33 facilities were from northern California and 67 were from southern California. Also, 85 facilities were part of a health system or network, 14 were freestanding, and 1 was a district facility. Facility types included 68 community hospitals, 17 long-term acute-care (LTAC) facilities, 17 academic or teaching hospitals, 4 critical-access hospitals, and 4 pediatric hospitals. There was an even distribution of hospital bed size: 35 facilities had &lt;250 beds. The final designations included 19 gold, 35 silver and 43 bronze designations. There was 44% incongruency in applicants not receiving the designation for which they applied. Community hospitals were 63%–74% of all designations, and no LTACs received a gold designation. Moreover, 63% of hospitals with gold designations had &gt;250 beds, and 47% of hospitals with bronze designations had &lt;1 25 beds. Conclusions: The number of applicants was higher than expected because the open enrollment period occurred during the COVID-19 pandemic. This finding demonstrates the high importance placed on antimicrobial stewardship among ACHs. It also provides insight into how facilities are performing and collaborating and how CDPH can support facilities to improve their ASP.Funding: NoDisclosures: None

Drivers of antibiotic use in Vietnam: implications for designing community interventions

IntroductionAntimicrobial resistance is a global challenge that threatens our ability to prevent and treat common infectious diseases. Vietnam is affected by high rates of antimicrobial resistant infections, driven by the...

Sleeping with the enemy: Will the COVID-19 pandemic turn the tide of antimicrobial-resistant infections?

Keywords: antimicrobial resistance, bacterial infections, COVID-19, epidemiology, preventionMots-clés : antibiorésistance, COVID-19, épidémiologie, infections bactériennes, prévention

A Novel Benzoxaborole Is Active against Escherichia coli and Binds to FabI.

To combat the looming crisis of antimicrobial-resistant infections, there is an urgent need for novel antimicrobial discovery and drug target identification. The benzoxaborole series was previously identified as an inhibitor of mycobacterial growth. Here, we demonstrate that a benzoxaborole is also active against the Gram-negative bacterium Escherichia coli in vitro. We isolated resistant mutants of E. coli and subjected them to whole-genome sequencing. We found mutations in the enoyl acyl carrier protein FabI. Mutations mapped around the active center site located close to the cofactor binding site. This site partially overlaps with the binding pocket of triclosan, a known FabI inhibitor. Similar to triclosan, the physical interaction of the benzoxaborole with FabI was dependent on the cofactor NAD+. Identification of the putative target of this compound in E. coli provides scope for further development and optimization of this series for Gram-negative pathogens.

Geographical information system and spatial\u2013temporal statistics for monitoring infectious agents in hospital: a model using Klebsiella pneumoniae complex

BackgroundThe emergence and spread of antimicrobial resistance and infectious agents have challenged hospitals in recent decades. Our aim was to investigate the circulation of target infectious agents using Geographic Information System (GIS) and spatial–temporal statistics to improve surveillance and control of healthcare-associated infection and of antimicrobial resistance (AMR), using Klebsiella pneumoniae complex as a model.MethodsA retrospective study carried out in a 450-bed federal, tertiary hospital, located in Rio de Janeiro. All isolates of K. pneumoniae complex from clinical and surveillance cultures of hospitalized patients between 2014 and 2016, identified by the use of Vitek-2 system (BioMérieux), were extracted from the hospital's microbiology laboratory database. A basic scaled map of the hospital’s physical structure was created in AutoCAD and converted to QGis software (version 2.18). Thereafter, bacteria according to resistance profiles and patients with carbapenem-resistant K. pneumoniae (CRKp) complex were georeferenced by intensive and nonintensive care wards. Space–time permutation probability scan tests were used for cluster signals detection.ResultsOf the total 759 studied isolates, a significant increase in the resistance profile of K. pneumoniae complex was detected during the studied years. We also identified two space–time clusters affecting adult and paediatric patients harbouring CRKp complex on different floors, unnoticed by regular antimicrobial resistance surveillance.ConclusionsIn-hospital GIS with space–time statistical analysis can be applied in hospitals. This spatial methodology has the potential to expand and facilitate early detection of hospital outbreaks and may become a new tool in combating AMR or hospital-acquired infection.

Population-level faecal metagenomic profiling as a tool to predict antimicrobial resistance in Enterobacterales isolates causing invasive infections: An exploratory study across Cambodia, Kenya, and the UK.

BackgroundAntimicrobial resistance (AMR) in Enterobacterales is a global health threat. Capacity for individual-level surveillance remains limited in many countries, whilst population-level surveillance approaches could inform empiric antibiotic treatment guidelines.MethodsIn this exploratory study, a novel approach to population-level prediction of AMR in Enterobacterales clinical isolates using metagenomic (Illumina) profiling of pooled DNA extracts from human faecal samples was developed and tested. Taxonomic and AMR gene profiles were used to derive taxonomy-adjusted population-level AMR metrics. Bayesian modelling, and model comparison based on cross-validation, were used to evaluate the capacity of each metric to predict the number of resistant Enterobacterales invasive infections at a population-level, using available bloodstream/cerebrospinal fluid infection data.FindingsPopulation metagenomes comprised samples from 177, 157, and 156 individuals in Kenya, the UK, and Cambodia, respectively, collected between September 2014 and April 2016. Clinical data from independent populations included 910, 3356 and 197 bacterial isolates from blood/cerebrospinal fluid infections in Kenya, the UK and Cambodia, respectively (samples collected between January 2010 and May 2017). Enterobacterales were common colonisers and pathogens, and faecal taxonomic/AMR gene distributions and proportions of antimicrobial-resistant Enterobacterales infections differed by setting. A model including terms reflecting the metagenomic abundance of the commonest clinical Enterobacterales species, and of AMR genes known to either increase the minimum inhibitory concentration (MIC) or confer clinically-relevant resistance, had a higher predictive performance in determining population-level resistance in clinical Enterobacterales isolates compared to models considering only AMR gene information, only taxonomic information, or an intercept-only baseline model (difference in expected log predictive density compared to best model, estimated using leave-one-out cross-validation: intercept-only model = -223 [95% credible interval (CI): -330,-116]; model considering only AMR gene information = -186 [95% CI: -281,-91]; model considering only taxonomic information = -151 [95% CI: -232,-69]).InterpretationWhilst our findings are exploratory and require validation, intermittent metagenomics of pooled samples could represent an effective approach for AMR surveillance and to predict population-level AMR in clinical isolates, complementary to ongoing development of laboratory infrastructures processing individual samples.

Pleiotropic Regulatory Genes as A Tool for Streptomyces Strains Bioprospecting and Improvement

Many taxa within class Actinobacteria, most notably genus Streptomyces, are known for the abundant presence of specialized biosynthetic pathways that convert essential cellular metabolites (amino acids, acyl moieties, such as acetyl-CoA, nucleotides etc.) into diverse natural products (NPs). NPs remain one of the pillars of modern pharmaceutical industry, and use of NPs as antibiotics is perhaps the most notable example of the commercial success of NPs. Nowadays, as humankind faces a formidable challenge to counter the rise of antimicrobial resistance and viral infections, there is renewed interest in streptomycetes as a source of novel NPs. This prompted the investigation of a variety of approaches to discover novel NPs and to improve the production of known ones. The focus of this review is on the use of regulatory genes to discover novel NPs. The two-layered scheme of regulation of NP biosynthesis is described and terms referring to cryptic NP gene cluster are detailed. Major players in global regulatory network are described as well as how their manipulation may be used to access the secondary metabolomes of Streptomyces and Actinobacteria in general. The value of studying the NP regulation in the era of synthetic biology is summarized in the last section.

Pre-formulation and delivery strategies for the development of bacteriocins as next generation antibiotics

Bacteriocins, a class of antimicrobial peptide produced by bacteria, may offer a potential alternative to traditional antibiotics, an important step towards mitigating the ever-increasing antimicrobial resistance crisis. They are active against a range of clinically relevant Gram-positive and Gram-negative bacteria. Bacteriocins have been discussed in the literature for over a century. Although they are used as preservatives in food, no medicine based on their antimicrobial activity exists on the market today. In order to formulate them into clinical antibiotics, pre-formulation studies on their biophysical and physicochemical properties that will influence their activity in vivo and their stability during manufacture must be elucidated. Thermal, pH and enzymatic stability of bacteriocins are commonly studied and regularly reported in the literature. Solubility, permeability and aggregation properties on the other hand are less frequently reported for many bacteriocins, which may contribute to their poor clinical progression. Promising cytotoxicity studies report that bacteriocins exhibit few cytotoxic effects on a variety of mammalian cell lines, at active concentrations. This review highlights the lack of quantitative data and in many cases even qualitative data, on bacteriocins’ solubility, stability, aggregation, permeability and cytotoxicity. The formulation strategies that have been explored to date, proposed routes of administration, trends in in vitro/in vivo behaviour and efforts in clinical development are discussed. The future promise of bacteriocins as a new generation of antibiotics may require tailored local delivery strategies to fulfil their potential as a force to combat antimicrobial-resistant bacterial infections.

Prevalence of Substandard Amoxicillin Oral Dosage Forms in the National Capital District of Papua New Guinea.

.Antibiotics are commonly reported as being substandard or falsified in low- to middle-income countries, having potential to contribute to the development of antimicrobial resistance and drug-resistant infections. Amoxicillin, used to treat a number of infections and listed by the WHO as an essential medicine, presented as a good drug candidate for this study. We aimed to measure the prevalence of substandard and falsified amoxicillin oral products (tablets, capsules, and suspensions) in the National Capital District of Papua New Guinea (PNG). These oral products were surveyed in 2018 and 2019 from retail pharmacies, private and public health facilities, and the Area Medical Store, representing more than 90% of licensed medicine outlets. The product packaging was visually inspected, and the samples were analyzed for amoxicillin content using a validated high-performance liquid chromatography method. Although no falsified products were identified, 15% of the 190 products analyzed contained substandard amounts of amoxicillin. Quality varied with the dosage form (P = 0.002), with capsules exhibiting the lowest incidence of substandard content (4% in 2019) and tablets collected in 2018 experiencing the highest failure rate (50%). Suspension (40%) quality was compromised by failure to achieve homogeneity on reconstitution. A higher incidence of substandard content (P = 0.002) was associated with one major retail group. Routine testing of medicines by resource-poor countries is often unachievable, leading to the circulation of poor quality drugs, which is a global public health concern. Our study highlighted that substandard amoxicillin oral products are indeed prevalent in the NCD of PNG.

Three-Dimensional Micropatterning Deters Early Bacterial Adherence and Can Eliminate Colonization.

Developing strategies to prevent bacterial infections that do not rely on the use of drugs is regarded globally as an important means to stem the tide of antimicrobial resistance, as argued by the World Health Organization (WHO) (Mendelson, M.; Matsoso, M. P. The World Health Organization Global Action Plan for Antimicrobial Resistance. S. Afr. Med. J. 2015, 105 (5), 325-325. DOI: 10.7196/SAMJ.9644). Given that many antimicrobial-resistant infections are caused by the bacterial colonization of indwelling medical devices such as catheters and ventilators, the use of microengineered surfaces to prevent the initial attachment of microbes to these devices is a promising solution. In this work, it is demonstrated that 3D engineered surfaces can inhibit the initial phases of surface colonization for Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, representing the three most common catheter-associated urinary tract bacterial infections, identified by the WHO as urgent threats. A variety of designs including 11 different topographies and configurations that exhibited random distributions, sharp protrusions, and/or curvilinear shapes with dimensions ranging between 500 nm and 2 μm were tested to better understand the initial stages of surface colonization and how to optimize the design of fabricated surfaces for improved inhibition. These topographies were fabricated in two configurations to obtain either a standard 2D cross section or a 3D engineered topography using a novel UV lithography process enabling cost-efficient high-throughput manufacturing. Evaluating both the number of adhered bacteria and microcolonies formed by all three bacterial pathogens on the different surfaces provides insight into the initial colonization phase of bacterial growth on the various surfaces. The results demonstrate that both initial attachment and subsequent colonization can be significantly reduced on concrete 3D engineered patterns when compared to flat substrates and standard 2D micropatterns. Thus, this technology has great potential to reduce the colonization of bacteria on surfaces in clinical settings without the need for chemical treatments that might enhance antimicrobial resistance.

Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa).

Antimicrobial-resistant infections are commonly encountered in US hospitals and result in significant morbidity and mortality. This guidance document provides recommendations for the treatment of infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated common questions regarding the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Based on review of the published literature and clinical experience, the panel provide recommendations and associated rationale for each recommendation. Because of significant differences in the molecular epidemiology of resistance and the availability of specific anti-infective agents globally, this document focuses on treatment of antimicrobial-resistant infections in the United States. Approaches to empiric treatment selection, duration of therapy, and other management considerations are briefly discussed. The majority of guidance focuses on preferred and alternative treatment recommendations for antimicrobial-resistant infections, assuming that the causative organism has been identified and antibiotic susceptibility testing results are known. Treatment recommendations apply to both adults and children. The field of antimicrobial resistance is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to challenge clinicians. This guidance document is current as of 17 September 2020. Updates to this guidance document will occur periodically as new data emerge. Furthermore, the panel will expand recommendations to include other problematic gram-negative pathogens in future versions. The most current version of the guidance including the date of publication can be found at www.idsociety.org/practice-guideline/amr-guidance/.

Evaluation of factors fuelling global antimicrobial resistance and its economic and clinical burden

The aim of the research is to assess the factors fuelling Antimicrobial Resistance (AMR) and its economic and clinical burden. For this purpose, a systematic review was conducted, which included an analysis of factors and economic and clinical burden of AMR. It was found that poorly treated sewage; discharges from antibiotic manufacturing plants, empirical prescribing, lack of antimicrobial stewardship, poor AMR monitoring; hospital-acquired infections and human-to-human contacts with environmental pathogens through food; and increase in global trade and travel are the factors behind the spread of AMR. Further, based on previous research, the study found a significant economic and clinical burden caused by AMR infections. It is recommended that well-organised antimicrobial stewardship be in place, AMR monitoring, limit access to antibiotics via over the counter dispensing without prescriptions, mandatory sensitivity tests for antimicrobial prescription be considered, proper hygiene in hospitals and medicine manufacturing sites must be ensured to reduce global AMR. Key words: Antimicrobial Resistance, antimicrobial resistance (AMR), antibiotic resistance, economic burden, clinical burden.

Acquisition of antimicrobial resistance determinants in Enterobacterales by international travelers from a large urban setting in Brazil

BackgroundAntimicrobial resistance is increased by international mobility. We present data about intestinal colonization of travelers departing from a middle-income country. MethodsTravelers were recruited from 2015 to 2019, collected an anal stool specimen and answered a questionnaire before and after travel. Enterobacterales isolates were investigated for antimicrobial resistance; extended-spectrum beta-lactamase (ESBL) and carbapenemase production; plasmid-encoded cephalosporinases (pAmpC), plasmid-mediated quinolone resistance (PMQR) and mcr genes by PCR and sequencing; and association with travel related variables. ResultsAmong 210 travelers, 26 (12%) carried multidrug-resistant Enterobacterales (MDR-E) and 18 (9%) ESBL-producing Enterobacterales (ESBL-E) before travel, with an increased prevalence from 1% to 11% over the study years. Acquisition of MDR-E and ESBL-E occurred in 59 (32%) and 43 (22%) travelers, respectively, mostly blaCTX-M-15 carrying Escherichia coli. One traveler acquired one isolate carrying blaOXA-181 gene, and two others, isolates carrying mcr-1. PMQR were detected in 14 isolates of returning travelers. The risk of MDR-E acquisition was higher in Southeast Asia and the Indian subcontinent, and after using antimicrobial agents. ConclusionWe describe an increasing pre-travel prevalence of ESBL-E colonization in subjects departing from this middle-income country over time. Travel to known risk areas and use of antimicrobial agents during travel were associated with acquisition of MDR-E. Travel advice is critical to mitigating this risk, as colonization by MDR-E may raise the chances of antimicrobial-resistant infections.

Emerging of bacterial resistance: an ongoing threat during and after the Syrian crisis.

The rapid emergence of bacterial resistance worldwide is a serious problem, leading to many therapeutic failures and rendering inactive effective antibiotics currently used . This problem has recently been accelerated by conflicts and its related migration. The antibiotic resistance phenomenon is diffused in Syria with a high rate of multi drug resistance cases in gram negative and gram positive organisms during and after the Syrian crisis as a result of misprescribing and overprescribing of antibiotics. The inappropriate use of antibiotic plays an important role in resistance generation. Hence, big efforts are urgently needed by using phenotypic and genetic analysis of bacterial strains against antibiotics to increase characterization and identification of mutant resistant strains and find new strategies to control the spread of antimicrobial resistance infections. This review highlights the antibacterial resistance problem in Syria, showing its negative impact and presenting a sum of efforts that are urgently needed to overcome this problem.