Antimicrobial-resistant Infections Research Articles

Epidemiology of infections and colonization caused by Klebsiella pneumoniae NDM in the Mazovian Voivodeship in 2016–2017

Abstract Introduction Klebsiella pneumoniae is a common cause of antimicrobial-resistant opportunistic infections in hospitalized patients. Due to acquired resistance to multiple antimicrobials, K. pneumoniae is a particular threat in health care. The aim of this study was the assessment of the epidemiological situation related to the spread of symptomatic infections and colonization caused by K. pneumoniae New Delhi metallo-β-lactamase (NDM) in the Mazovian Voivodeship in 2016–2017. Materials and Methods The study included data collected between 2016 and 2017 from 168 hospitals located in and outside of Warsaw but limited to the Mazovian Voivodeship. Data was extracted from reports on suspected epidemic outbreaks and the elimination of outbreaks as well as annual reports on nosocomial infections and alarm pathogens. Results The incidence of infections caused by K. pneumoniae NDM (symptomatic and asymptomatic) was 0.96/1,000 hospitalizations in 2016 and 2.04/1,000 hospitalizations in 2017. In 2016, hospitals in the Mazovian Voivodeship reported 50 transmissions of K. pneumoniae NDM. In 2017, this value increased to 74. The risk of symptomatic infection was higher in hospitals outside of Warsaw than in hospitals in Warsaw, while risk of colonization was higher in hospitals in Warsaw. Conclusions The epidemiological situation related to infections and colonization caused by K. pneumoniae NDM in the Mazovian Voivodeship is disadvantageous, which implies the necessity to monitor anti-epidemic measures. The epidemic situation in hospitals outside of Warsaw seems to be worse compared to hospitals in Warsaw, which have higher risks of symptomatic infection caused by K. pneumoniae NDM.

Phage therapy in tackling AMR: Potential and prospects

Bacteriophages, usually known as phages, are the natural predators of bacteria. They reside in the habitats where bacteria are found and are abundant in nature including soil, water, sewage, etc. It has been estimated that the number of phages that have been isolated and characterized, likely represent only a tiny fraction of the overall diversity. A glimpse of the large range of applications of phages in the field of biotechnology and medical science especially when we are facing bottleneck in modern drug therapy due to wider-scale antimicrobial resistance (AMR) against antibiotics, gives us a hope to venture in exploiting the potential of our most versatile heritage, which has been a lifeline of millions from centuries. Researchers believe that besides phages as therapeutics, their encoded endolysins can also be used as therapeutic formulations thus having a potential to replace antibiotics. Phage therapy has been revitalized and it offers an affordable alternative strategy for combating emerging AMR infections.

POSC124 Economic Burden of Antimicrobial Resistance: An Analysis of the Additional Bed Day Costs Associated with Treating Resistant Infections in Ireland

Antimicrobial resistance (AMR) is a global public health concern that can lead to increased morbidity and mortality. Patients with antimicrobial-resistant infections typically require longer hospital admissions, which may impact other health services. We estimated the additional bed day costs associated with treating resistant relative to susceptible infections in Ireland.

Overview of Antimicrobial Compounds Produced from Bacteria

Every year more than 10 million lives are lost due to antimicrobial-resistant infections. Therefore, the development of antimicrobial agents has become a necessity. Natural products are being used as therapeutic agents. Antimicrobial beings are one of the most compelling molecules. Microorganisms produce bioactive compounds with antimicrobial and cytotoxic bioactivity. Fungi and bacteria are mostly used as novel antimicrobial agents. In the years 1940 & 1950 marine bacteria were shown to produce antimicrobial compounds. The first marine antibacterials were identified in the year 1960, and in the year 1970 their antibiotic properties has been reported. The majority of identified compounds were isolated from Actinobacteria & Bacilli. The interesting fact is that the molecules that were active against gram-negative were isolated from Bacilli. It is estimated at least 4-5% of the genome of any strain of the B. subtilus group is devoted to antimicrobial compounds (AMCs) production.

Infectious Diseases Society of America Guidance on the Treatment of AmpC β-Lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections.

The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on 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). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggested approaches and corresponding rationales. In contrast to guidance in the previous document, published data on the optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as "suggested approaches" based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of 17 September 2021 and will be updated annually. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.

181. Demographic and Geographic Epidemiology of Staphylococcus aureus Bacteremia using Geographic Information Systems Mapping and Spatial Statistics

BackgroundRisk factors for community-associated Staphylococcus aureus bacteremia (SAB) are incompletely understood. We used Geographic Information Systems (GIS) and spatial statistics to analyze demographic and geographic epidemiology of SAB in the community.MethodsWe used the S. aureus Bacteremia Group Prospective Cohort Study (SABG-PCS) at Duke University Medical Center to obtain demographic and clinical data. We used the American Community Survey and U.S. Census to supply neighborhood variables. Secular trends in demographic and clinical characteristics of SAB patients prospectively enrolled between 1995 and 2015 (n = 2478) were determined using linear regressions. To characterize spatial patterns in Methicillin-resistant S. aureus (MRSA) bacteremia compared to Methicillin-susceptible S. aureus (MSSA) bacteremia, we used GIS mapping and selected a subgroup of patients (n = 667) living in and around Durham County, North Carolina. We then created generalized additive models (GAMs) using this subgroup to detect geographic heterogeneities in probabilities of MRSA infections compared to MSSA infections.ResultsWe found evidence of changing demographic and clinical characteristics of SAB patients over the 21-year period. The proportion of infections acquired in the community increased significantly (p < 0.0001). However, we did not detect spatial heterogeneities of MRSA infections in Durham County. Patient location of residence was not significantly associated with antimicrobial-resistant infections. Patient age and year of hospital admission were the only statistically significant covariates in our spatial models.ConclusionWe utilized a novel method to analyze SAB in the community using GIS and spatial statistics. Future research should prioritize community transmission of S. aureus to identify robust risk factors for infection.Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant)

753. Impact of COVID-19 on Healthcare Facility-Onset Clostridiodes difficile Infection

BackgroundIt is estimated that the majority of hospitalized COVID-19 patients around the world received antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased antimicrobial resistance and Clostridioides difficile infections (CDI). Gastrointestinal symptoms of COVID-19 may also contribute to increased testing. The objective of this study was to assess the impact of the COVID-19 pandemic on our healthcare facility-onset (HO) CDI rates.MethodsThis was a retrospective cross-sectional study comparing CDI rate per 1,000 patient days, C. diff order rate per 1,000 patient days, Standardized Antimicrobial Administration Ratio (SAAR), and Standardized Infection Ratio (SIR) in the pre-COVID-19 period from January 1, 2019 to December 31, 2019 to the COVID-19 period from April 1, 2020 to March 31, 2021 at a 877-bed tertiary care hospital in Detroit, Michigan. CDI and order rates were extracted from the electronic medical record (Epic™ Bugsy). SAAR and SIR data were extracted from National Healthcare Safety Network (NHSN).ResultsThe average CDI rate per 1,000 patient days was 4.29 pre-COVID-19 compared to 1.98 during COVID-19 with a 54% reduction, and the C. diff order rate per 1,000 patient days also decreased from 130.89 to 93.03, resulting in a 29% reduction (Figure 1). The SIR was 0.383 compared to 0.308 during COVID-19 (P-value 0.404). SAAR decreased from 1.095 to 0.945 (P-value < 0.001). However, our institution experienced three COVID-19 waves, with peaks in April 2020, November 2020 and March 2021, that correlated with high risk CDI antibiotic utilization in intensive care unit (ICU) (Figure 2). The average hand hygiene rate increased from 82% to 92%. Figure 1. Clostridioides difficile order and infection rates pre-and during COVID-19 pandemic. Figure 2. Standardized Antimicrobial Administration Ratio (SAAR) pre-and during COVID-19 pandemic.ConclusionDespite the COVID-19 pandemic, the HO-CDI and C. diff order rates and overall SAAR decreased; however, antibiotic utilization increased in the ICU during the COVID-19 waves. The overall decrease may be multifactorial and related to increased hand hygiene compliance, isolation and personal protective equipment use and overall decreased antibiotic use and C. diff orders.Disclosures Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

129. Antimicrobial Resistance Genes Were Reduced Following Administration of Investigational Microbiota-Based Live Biotherapeutic RBX2660 to Individuals with Recurrent Clostridioides difficile Infection

BackgroundIntestinal colonization by antimicrobial resistant (AMR) pathogens is a known health and infection risk, and is common among individuals with recurrent Clostridioides difficile infections (rCDI). Accordingly, therapeutic approaches that decolonize the gut of AMR pathogens could be valuable to patients to reduce risk of associated illnesses. Herein, we assessed gut colonization with AMR bacteria before and after treatment with RBX2660—a microbiota-based investigational live biotherapeutic—in the PUNCH CD3 Phase 3 trial for reducing CDI recurrence.MethodsrCDI participants enrolled in PUNCH CD3 received a blinded single dose of RBX2660 or placebo within 24 to 72 hours after completing antibiotic treatment for the most recent rCDI episode. Clinical response was the absence of CDI recurrence at eight weeks after treatment, and participants were asked to submit stool samples prior to RBX2660 or placebo treatment (baseline) and 1, 4 and 8 weeks, 3 and 6 months after study treatment. Samples were extracted and sequenced using a shallow shotgun method. The presence and number of AMR genes was determined for 175 participant samples and 116 RBX2660 samples using 90% K-mer sequence coverage based on the MEGARes database. AMR gene count data were collapsed into count columns to adjust for sparseness in the matrices and were analyzed using a Generalized Linear Mixed Model.ResultsClinically, RBX2660 demonstrated superior efficacy versus placebo (70.4% and 58.1%, respectively), and the total AMR genes per participant decreased significantly from before to after treatment in RBX2660-treated responders (p< .05, Figure 1) and remained low to at least 6 months. Among genes that decreased in RBX2660 responders were clinically important extended-spectrum beta-lactamase (blaTEM, blaSHV, blaCTX-M), vancomycin resistance (vanA, vanB), and fluoroquinolone resistance genes (gyrA, parC). Total AMR genes per PUNCH CD3 participant among RBX2660-treated responders at the indicated time points and in the RBX2660 investigational product. The red lines indicate timepoint group medians.ConclusionIn the PUNCH CD3 Phase 3 trial of RBX2660 for rCDI, AMR gene content decreased after RBX2660 treatment and remained low to at least 6 months, consistent with prior RBX2660 trials. This underscores the potential of microbiota-based biotherapeutics for decolonizing AMR bacteria from gut microbiota and thereby reducing AMR infection risks.Disclosures Heidi Hau, PhD, Rebiotix Inc. (Employee) Dana M. Walsh, PhD, Rebiotix (Employee) Ken Blount, PhD, Rebiotix Inc., a Ferring Company (Employee)

Differences of virulence factors, and antimicrobial susceptibility according to phylogenetic group in uropathogenic Escherichia coli strains isolated from Korean patients

BackgroundEscherichia coli is among the most common uropathogens. Increased antibiotic resistance in Gram negative bacilli is global concern. Alternative therapeutic options including vaccines against uropathogenic E. coli (UPEC) have been developed. In this study, we compared the genotypic characteristics and antimicrobial susceptibility of UPEC according to phylogenetic groups.MethodsWe retrospectively reviewed the medical records of pyelonephritis patients with UPEC between February 2015 and June 2018. The study was conducted at a medical center in Korea. We compared the clinical and genotypic characteristics of UPEC according to phylogenetic groups. The phylogenetic groups and 29 virulence factors were identified using multiplex polymerase chain reaction.ResultsPhylogenetic group analysis revealed that most uropathogenic E. coli belonged to groups B2 and D: B2 (276, 77.7%), D (62, 17.5%), B1 (12, 3.4%), and A (5, 1.4%). Among the virulence factors, fyuA, fimH, traT, iutA, papG allele II, and papC were the most frequently observed. Phylogenetic group B2 was more closely related to virulence factors, including fimH, sfa/focED, focG, hlyA, cnf1, fyuA, and PAI, than group D. Groups B2 and D showed similar clinical presentations and complications. Group B2 had mostly healthcare-associated infections and antimicrobial resistance. Group D mostly had community-acquired infections. The K1 serotype was prevalent in group B2, and K5 was the most prevalent in group D.ConclusionsPhylogenetic group B2 had more proportions and types of virulence factors than group D. Group B2 showed a high presentation of virulence factors related to adhesions and toxins. An increased presentation of antimicrobial resistance and healthcare-associated infections was also noted. Considering the genetic characteristics of UPEC, alternative therapeutic options targeting frequent virulence factors might be considered in addition to antibiotics.

Change in Antimicrobial Use During COVID-19 Pandemic in South Carolina Hospitals: A Multicenter Observational Cohort Study

ObjectivesThis retrospective cohort study examined the impact of the pandemic on antimicrobial use (AU) in South Carolina hospitals. MethodsAntimicrobial use in days of therapy (DOT) per 1000 days-present was evaluated in 17 hospitals in South Carolina. Matched-pairs mean difference was used to compare AU during the pandemic (March–June 2020) with that during the same months in 2019 in hospitals that did and did not admit patients with COVID-19. ResultsThere was a 6.6% increase in overall AU in the seven hospitals that admitted patients with COVID-19 (from 530.9 to 565.8; mean difference (MD) 34.9 DOT/1000 days-present; 95% CI 4.3, 65.6; P = 0.03). There was no significant change in overall AU in the remaining 10 hospitals that did not admit patients with COVID-19 (MD 6.0 DOT/1000 days-present; 95% CI –55.5, 67.6; P = 0.83). Most of the increase in AU in the seven hospitals that admitted patients with COVID-19 was observed in broad-spectrum antimicrobial agents. A 16.4% increase was observed in agents predominantly used for hospital-onset infections (from 122.3 to 142.5; MD 20.1 DOT/1000 days-present; 95% CI 11.1, 29.1; P = 0.002). There was also a 9.9% increase in the use of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents (from 66.7 to 73.3; MD 6.6 DOT/1000 days-present; 95% CI 2.3, 10.8; P = 0.01). ConclusionThe COVID-19 pandemic appears to drive overall and broad-spectrum antimicrobial use in South Carolina hospitals admitting patients with COVID-19. Additional antimicrobial stewardship resources are needed to curtail excessive antimicrobial use in hospitals to prevent subsequent increases in antimicrobial resistance and Clostridioides difficile infection rates, given the continuing nature of the pandemic.

The Requirement of Genetic Diagnostic Technologies for Environmental Surveillance of Antimicrobial Resistance

Antimicrobial resistance (AMR) is threatening modern medicine. While the primary cost of AMR is paid in the healthcare domain, the agricultural and environmental domains are also reservoirs of resistant microorganisms and hence perpetual sources of AMR infections in humans. Consequently, the World Health Organisation and other international agencies are calling for surveillance of AMR in all three domains to guide intervention and risk reduction strategies. Technologies for detecting AMR that have been developed for healthcare settings are not immediately transferable to environmental and agricultural settings, and limited dialogue between the domains has hampered opportunities for cross-fertilisation to develop modified or new technologies. In this feature, we discuss the limitations of currently available AMR sensing technologies used in the clinic for sensing in other environments, and what is required to overcome these limitations.

Gut Microbiota is an Important Source of Bacteriocins and Their In Situ Expression Can Be Explored for Treatment of Bacterial Infections

Bacteriocins are interesting natural antimicrobial peptides that could be deployed quickly to combat certain antimicrobial-resistant bacterial infections. These molecules could be used in conjunction with traditional antibiotics, or even to replace them in some circumstances. To strengthen the concept of "bacteriocinotherapy," we discuss here the benefits associated with production in situ of bacteriocins by commensal bacteria. This on sites production capacity could augment the gut microbiota global resistance plan and provide a backup for bacterial infection treatments.

PBI-017 - Differences of virulence factors, and antimicrobial susceptibility according to phylogenetic group in uropathogenic Escherichia coli strains isolated from Korean patients

Background Escherichia coli is among the most common uropathogens. Increased antibiotic resistance in Gram negative bacilli is global concern. Alternative therapeutic options including vaccines against uropathogenic E. coli (UPEC) have been developed. In this study, we compared the genotypic characteristics and antimicrobial susceptibility of UPEC according to phylogenetic groups. Methods We retrospectively reviewed the medical records of pyelonephritis patients with UPEC between February 2015 and June 2018. The study was conducted at a medical center in Korea. We compared the clinical and genotypic characteristics of UPEC according to phylogenetic groups. The phylogenetic groups and 29 virulence factors were identified using multiplex polymerase chain reaction. Results Phylogenetic group analysis revealed that most uropathogenic E. coli belonged to groups B2 and D: B2 (276, 77.7%), D (62, 17.5%), B1 (12, 3.4%), and A (5, 1.4%). Among the virulence factors, fyuA, fimH, traT, iutA, papG allele II, and papC were the most frequently observed. Phylogenetic group B2 was more closely related to virulence factors, including fimH, sfa/focED, focG, hlyA, cnf1, fyuA, and PAI, than group D. Groups B2 and D showed similar clinical presentations and complications. Group B2 had mostly healthcare-associated infections and antimicrobial resistance. Group D mostly had community-acquired infections. The K1 serotype was prevalent in group B2, and K5 was the most prevalent in group D. Conclusions Phylogenetic group B2 had more proportions and types of virulence factors than group D. Group B2 showed a high presentation of virulence factors related to adhesions and toxins. An increased presentation of antimicrobial resistance and healthcare-associated infections was also noted. Considering the genetic characteristics of UPEC, alternative therapeutic options targeting frequent virulence factors might be considered in addition to antibiotics.

Impact of Anatomic Site, Specimen Collection Timing, and Patient Symptom Status on Neisseria gonorrhoeae Culture Recovery.

Neisseria gonorrhoeae culture is required for antimicrobial susceptibility testing, but recovering isolates from clinical specimens is challenging. Although many variables influence culture recovery, studies evaluating the impact of culture specimen collection timing and patient symptom status are limited. This study analyzed urogenital and extragenital culture recovery data from Centers for Disease Control and Prevention's Strengthening the US Response to Resistant Gonorrhea (SURRG) program, a multisite project, which enhances local N. gonorrhoeae culture and antimicrobial susceptibility testing capacity. Eight SURRG jurisdictions collected gonococcal cultures from patients with N. gonorrhoeae-positive nucleic acid amplification test (NAAT) results attending sexually transmitted disease and community clinics. Matched NAAT and culture specimens from the same anatomic site were collected, and culture recovery was assessed. Time between NAAT and culture specimen collection was categorized as same day, 1 to 7 days, 8 to 14 days, or ≥15 days, and patient symptoms were matched to the anatomic site where culture specimens were collected. From 2018 to 2019, among persons with N. gonorrhoeae-positive NAAT, urethral infections resulted in the highest culture recovery (5927 of 6515 [91.0%]), followed by endocervical (222 of 363 [61.2%]), vaginal (63 of 133 [47.4%]), rectal (1117 of 2805 [39.8%]), and pharyngeal (1019 of 3678 [27.7%]) infections. Culture recovery was highest when specimens were collected on the same day as NAAT specimens and significantly decreased after 7 days. Symptoms were significantly associated with culture recovery at urethral (P = <0.0001) and rectal (P = <0.0001) sites of infection but not endocervical, vaginal, or pharyngeal sites. Culture specimen collection timing and patient symptomatic status can impact culture recovery. These findings can guide decisions about culture collection protocols to maximize culture recovery and strengthen detection of antimicrobial-resistant infections.

Infection Prevention and Antimicrobial Stewardship Program Collaboration During the COVID-19 Pandemic: a Window of Opportunity.

Purpose of ReviewWe describe the similarities between antimicrobial stewardship programs (ASPs) and infection prevention programs (IPPs), and we discuss how these similarities lend themselves to synergy between programs. We also discuss how the COVID-19 pandemic has generated further opportunities for future collaborations that could benefit both programs.Recent FindingsThe COVID-19 pandemic has created new needs, such as real-time data and access to personnel important to both programs, such as information technologists and infectious diseases specialists. It has also increased concerns about rising rates of antimicrobial resistance and healthcare-associated infections, both of which overlap significantly and are key focus areas for both ASPs and IPPs. These emergent issues have highlighted the need for enhanced program infrastructure and new team models. The shift towards telecommunication and telework has facilitated the creation of enhanced infrastructures for collaboration on activities ranging from data access and reporting to providing telehealth services to remote hospitals. These enhanced infrastructures can be leveraged in future collaborative efforts between ASPs and IPPs.SummaryCollaboration between IPPs and ASPs can mitigate setbacks experienced by health systems during the current pandemic, enhance the performance of both programs in the post-pandemic era and increase their preparedness for future pandemic threats. As health systems plan for the post-pandemic era, they should invest in opportunities for synergy between ASPs and IPPs highlighted during the pandemic.

Comparative insights into multiple drug resistance determinants in Stenotrophomonas maltophilia MER1

ObjectivesMultidrug-resistant (MDR) Stenotrophomonas maltophilia strain MER1 was isolated from hospital wastewater in Shandong Province, China. This study aimed to determine the genetic determinants related to its striking MDR phenotype. MethodsAntimicrobial susceptibility testing of strain MER1 was performed by disk diffusion on Mueller–Hinton agar plates, and MICs were interpreted according to Clinical and Laboratory Standards Institute breakpoints. The genome of MER1 was sequenced and assembled using PacBio RS II and BGISEQ-500 platforms. Antimicrobial resistance determinants together with other transferability or adaptability determinants were identified by comparative genomics. Phylogenetic and contextual assays for these elements were conducted to assess the risk of spread of MER1. ResultsAntimicrobial susceptibility testing revealed that strain MER1 is resistant to nine different antibiotics, including ampicillin, meropenem, amikacin, erythromycin, vancomycin, tetracycline, tigecycline, colistin and ceftazidime. Several genes were identified encoding efflux pumps and drug-inactivating agents, accounting for resistance to the above antibiotics, including meropenem, tigecycline and colistin regarded as last-line therapies for infections caused by MDR Gram-negative bacteria. MER1 co-harbours two non-mobile mcr homologues. A novel genomic region of variability was demonstrated to confer bacterial robustness and adaptability upon strain MER1. ConclusionCollective efforts revealed the MDR properties and potential genetic determinants of S. maltophilia MER1 isolated from hospital wastewater. Comparative genomic analysis of S. maltophilia MER1 may provide insights into the prevention and treatment of antimicrobial-resistant infections. Our findings raise concern that the MDR genes in the reservoir of S. maltophilia may further spread into various ecological niches or medically high-risk pathogens.

Antimicrobial resistance in Bacillus-based biopesticide products.

The crisis of antimicrobial resistant bacterial infections is one of the most pressing public health issues. Common agricultural practices have been implicated in the generation of antimicrobial resistant bacteria. Biopesticides, live bacteria used for pest control, are non-pathogenic and considered safe for consumption. Application of bacteria-based pesticides to crops in high concentrations raises the possibility of unintentional contributions to the movement and generation of antimicrobial resistance genes in the environment. However, the presence of clinically relevant antimicrobial resistance genes and their resistance phenotypes are currently unknown. Here we use a combination of multiple bioinformatic and microbiological techniques to define resistomes of widely used biopesticides and determine how the presence of suspected antimicrobial resistance genes translates to observable resistance phenotypes in several biopesticide products. Our results demonstrate that biopesticide products are reservoirs of clinically relevant antimicrobial resistance genes and bear resistance to multiple drug classes.

Prevalence and mechanisms of antibiotic resistance in Escherichia coli isolated from mastitic dairy cattle in Canada

BackgroundBovine mastitis is the most common infectious disease in dairy cattle with major economic implications for the dairy industry worldwide. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from dairy farms is vital not only for animal husbandry but also for public health.MethodsIn this study, the prevalence of AMR in 113 Escherichia coli isolates from cases of bovine clinical mastitis in Canada was investigated. Kirby-Bauer disk diffusion test with 18 antibiotics and microdilution method with 3 heavy metals (copper, zinc, and silver) was performed to determine the antibiotic and heavy-metal susceptibility. Resistant strains were assessed for efflux and ß-lactamase activities besides assessing biofilm formation and hemolysis. Whole-genome sequences for each of the isolates were examined to detect the presence of genes corresponding to the observed AMR and virulence factors.ResultsPhenotypic analysis revealed that 32 isolates were resistant to one or more antibiotics and 107 showed resistance against at least one heavy metal. Quinolones and silver were the most efficient against the tested isolates. Among the AMR isolates, AcrAB-TolC efflux activity and ß-lactamase enzyme activities were detected in 13 and 14 isolates, respectively. All isolates produced biofilm but with different capacities, and 33 isolates showed α-hemolysin activity. A positive correlation (Pearson r = + 0.89) between efflux pump activity and quantity of biofilm was observed. Genes associated with aggregation, adhesion, cyclic di-GMP, quorum sensing were detected in the AMR isolates corroborating phenotype observations.ConclusionsThis investigation showed the prevalence of AMR in E. coli isolates from bovine clinical mastitis. The results also suggest the inadequacy of antimicrobials with a single mode of action to curtail AMR bacteria with multiple mechanisms of resistance and virulence factors. Therefore, it calls for combinatorial therapy for the effective management of AMR infections in dairy farms and combats its potential transmission to the food supply chain through the milk and dairy products.

Associations of Antimicrobial-Resistant Gram-Negative Bloodstream Infections with Outcomes among Hospitalized Pediatric Patients in the United States

Abstract Objective The aim of this study was to assess the impact of pediatric antimicrobial-resistant gram-negative bloodstream infections (GNBSIs). Methods A retrospective cohort study (2009–2016) was conducted using the Premier Healthcare Database among pediatric admissions with GNBSIs at hospitals reporting microbiology data. Infections for neonates and nonneonates were classified as multidrug resistance (MDR), resistant to one or two antibiotic drug classes (1–2DR), or susceptible. Results Among 1,276 GNBSIs, 266 (20.8%) infections were 1–2DR and 23 (1.8%) MDR. Compared with susceptible GNBSIs, MDR nonneonates had higher mortality and higher costs, whereas 1–2DR neonates had longer stays and higher costs. Conclusions Antimicrobial-resistant GNBSIs were associated with worse outcomes among pediatric hospitalized patients.

Alternatives to Conventional Antibiotic Therapy: Potential Therapeutic Strategies of Combating Antimicrobial-Resistance and Biofilm-Related Infections.

Antibiotics have been denoted as the orthodox therapeutic agents for fighting bacteria-related infections in clinical practices for decades. Nevertheless, overuse of antibiotics has led to the upsurge of species with antimicrobial resistance (AMR) or multi-drug resistance. Bacteria can also grow into the biofilm, which accounts for at least two-thirds of infections. Distinct gene expression and self-produced heterogeneous hydrated extracellular polymeric substance matrix architecture of biofilm contribute to their tolerance and externally manifest as antibiotic resistance. In this review, the difficulties in combating biofilm formation and AMR are introduced, and novel alternatives to antibiotics such as metal nanoparticles and quaternary ammonium compounds, chitosan and its derivatives, antimicrobial peptides, stimuli-responsive materials, phage therapy and other therapeutic strategies, from compounds to hydrogel, from inorganic to biological, are discussed. We expect to provide useful information for the readers who are seeking for solutions to the problem of AMR and biofilm-related infections.