Classes Of Antibiotics Research Articles

Emergence of MDR Enterobacter hormaechei RSM5 in Pharma Effluent and its Implications in β-lactam Antibiotic Removal from Effluent.

Antibiotic resistance poses the biggest threats to global health and development and also to food security. β-lactam antibiotics (BLAs) responsible for the transpeptidation/cross-linking process during cell wall biosynthesis contribute to the maximum resistance. The production of β-lactamase enzyme is a significant contributing factor to the development of antibiotic resistance to β-lactam antibiotics. Unintentional disposal of antibiotics from the manufacturing units of pharma industries to the water bodies enhances the exposure of antibiotics, contributing to resistance. This study describes the presence of > 50 antibiotic-resistant bacterial strains in pharma effluent of Himachal Pradesh, India. Among 54 isolates, 40% showed ampicillin resistance above 100µg/mL, 13% showed resistance above 5000µg/mL, and 3 strains showed resistance at 15,000µg/mL of ampicillin. Enterobacter hormaechei RSM5 showed the highest minimum inhibitory concentration (MIC) and cell viability and was selected for further studies. It produces lactamase (0.24 U/mL) to resist the higher concentration of antibiotics present in the media/effluent and demonstrated resistance against 3 different classes of antibiotics, confirming its status as a multidrug resistance (MDR) strain. The high-performance liquid chromatography (HPLC) analysis of the isolate demonstrated that Enterobacter hormaechei RSM5 can degrade ampicillin within 24h of incubation in medium/effluent. The emergence of Enterobacter as a pathogen with antibiotic resistance poses a significant health concern that could also be explored for the removal of antibiotics from the effluent at the source. The future of research in this area needs to be open and mindful of new approaches.

C10-Benzoate Esters of Anhydrotetracycline Inhibit Tetracycline Destructases and Recover Tetracycline Antibacterial Activity.

Tetracyclines (TCs) are an important class of antibiotics threatened by enzymatic inactivation. These tetracycline-inactivating enzymes, also known as tetracycline destructases (TDases), are a subfamily of class A flavin monooxygenases (FMOs) that catalyze hydroxyl group transfer and oxygen insertion (Baeyer-Villiger type) reactions on TC substrate scaffolds. Semisynthetic modification of TCs (e.g., tigecycline, omadacycline, eravacycline, and sarecycline) has proven effective in evading certain resistance mechanisms, such as ribosomal protection and efflux, but does not protect against TDase-mediated resistance. Here, we report the design, synthesis, and evaluation of a new series of 22 semisynthetic TDase inhibitors that explore D-ring substitution of anhydrotetracycline (aTC) including 14 C10-benzoate ester and eight C9-benzamides. Overall, the C10-benzoate esters displayed enhanced bioactivity and water solubility compared to the corresponding C9-benzamides featuring the same heterocyclic aryl side chains. The C10-benzoate ester derivatives of aTC were prepared in a high-yield one-step synthesis without the need for protecting groups. The C10-esters are water-soluble, stable toward hydrolysis, and display dose-dependent rescue of tetracycline antibiotic activity in E. coli expressing two types of tetracycline destructases, represented by TetX7 (Type 1) and Tet50 (Type 2). The best inhibitors recovered tetracycline antibiotic activity at concentrations as low as 2 μM, producing synergistic scores <0.5 in the fractional inhibitory concentration index (FICI) against TDase-expressing strains of E. coli and clinical P. aeruginosa. The C10-benzoate ester derivatives of aTC reported here are promising new leads for the development of tetracycline drug combination therapies to overcome TDase-mediated antibiotic resistance.

Prevalence and Multidrug Resistance in Non-Typhoidal Salmonella in India: A 20-Year Outlook

Non-typhoidal Salmonella (NTS) infection poses a significant public health challenge globally, particularly in developing countries like India. NTS, predominantly represented by S. enterica serovars, is a major cause of intestinal and extra-intestinal infections. This review provides a comprehensive overview of longitudinal analyses of the prevalence of NTS in different regions of India encountered in the last 20 years and their antimicrobial resistance patterns. We followed several research investigations published during 2000–2024 to examine the incidence and prevalence of different serovars of NTS in several parts of India and followed published articles on NTS showing resistance to different antibiotics. We pointed out NTS serovars, which are predominantly isolated in various human and non-human sources, as observed in several investigations conducted in different regions of India. Our analysis revealed that, among serovars detected from various sources, S. Typhimurium is the most predominant one occurring across both human and non-human sources, followed by S. Enteritidis and S. Weltevreden. The occurrence of similar serovars of Salmonella in both human and non-human sources may be due to zoonotic transmission between animals and humans. Extensive research conducted across many geographic locations reveals that NTS isolates exhibit resistance to several antibiotics, with multidrug-resistance (MDR) being more common. These MDR strains basically show resistance to three or more classes of antibiotics, including critically important antimicrobials such as nalidixic acid, ciprofloxacin, and third-generation cephalosporins. Temporal trends suggest an alarming increase in resistance to these antibiotics, particularly in serovars such as S. Typhimurium and S. Enteritidis. Overall, the current article sheds light on the urgent need for surveillance, judicious antibiotic use, and the development of alternative treatment strategies to combat the rising tide of antibiotic-resistant NTS strains.

Antibiotics change the population growth rate heterogeneity and morphology of bacteria.

A better understanding of the system-level effects of antibiotics on bacterial cells is essential to address the growing challenge of antibiotic resistance. Utilising Multipad Agarose Plate (MAP) platforms, we monitor the growth rate and cell morphology of three clinically relevant species (E.coli, S.aureus and P.aeruginosa) following exposure to 14 antibiotics across 11 concentrations (31 microbe-antibiotic combinations in total). Our results reveal a consistent increase in population growth rate heterogeneity (PGRH) as drug concentrations approach the minimum inhibitory concentration (MIC). Strikingly, the magnitude of this heterogeneity correlates with the functional distance between the ribosome and the specific cellular processes targeted by the antibiotics. Among the seven antibiotic classes studied, protein synthesis inhibitors and disruptors cause the lowest PGRH, while heterogeneity progressively increases with RNA synthesis inhibitors, DNA replication inhibitors, cell membrane disruptors and cell wall synthesis inhibitors. Because the ribosome is central to growth rate control, we hypothesize that heterogeneity might arise at the system level as a result of the propagation of damage to protein synthesis. Low heterogeneity is desirable from a clinical perspective, as high heterogeneity is often associated with persistence and treatment survival. Additionally, we observed a strong correlation between morphological alterations and growth inhibition across all antibiotics and species tested. This led to the development of a novel morphological parameter, MOR50, which enables rapid estimation of MIC for antibiotic susceptibility testing (AST) with a single snapshot after just 2.5 hours of incubation. In addition to introducing a novel, resource-efficient and rapid AST method, our findings shed new light on the system-level effects of antibiotic perturbations on bacteria, which might inform treatment design.

Effect of oral antibiotics after two-stage revision for periprosthetic joint infection on subsequent antibiotic resistance within a national cohort of United States veterans

Abstract. Background: Prior studies have indicated that administration of prolonged courses of oral antibiotics after Stage 2 reimplantation surgery for periprosthetic joint infection (PJI) results in a lower rate of recurrent PJI. However, there is concern that this antibiotic usage results in an increased risk of antibiotic resistance in any subsequent PJI that does occur. Methods: We retrospectively reviewed patients who underwent Stage 2 reimplantation surgery for PJI within the national Veterans Affairs hospital system of the United States. We compared those who received at least 2 weeks of oral antibiotics after Stage 2 reimplantation to those who did not. The primary outcome was the proportion of organisms resistant to four classes of antibiotics (tetracyclines, fluoroquinolones, oral beta-lactams, and sulfonamides) in recurrent PJI. Secondary outcomes included recurrent PJI and death. Results: Of the 605 patients who underwent Stage 2 reimplantation for PJI, 154 patients received at least 14 d of antibiotics after surgery and 451 patients did not. Bacteria causing recurrent PJI in patients who received prolonged antibiotics were more likely to be resistant to tetracyclines and trimethoprim–sulfamethoxazole but not oral beta-lactams or fluoroquinolones. There was no difference in risk of recurrent PJI or death between the two groups. Conclusions: Prolonged oral antibiotic treatment after Stage 2 reimplantation increases the risk of antibiotic resistance to some antibiotics in subsequent PJI. We recommend further research to identify the best choice of antibiotic and duration after Stage 2 reimplantation, to maximize benefits while minimizing risks.

Detection of AdeAB, TetA, and TetB efflux pump genes in clinical isolates of tetracycline-resistant Acinetobacter baumannii from patients of Suez Canal University Hospitals

BackgroundAcinetobacter baumannii is an opportunistic bacteria associated primarily with hospital-acquired infections. Its tendency to acquire or donate resistance genes to neighboring bacteria is a major concern. Tetracyclines have shown promise in treating A. baumannii infections, but tetracycline resistance is growing globally in A. baumannii isolates.ObjectivesThe study aimed to study (1) the prevalence of multidrug-resistant (MDR) A. baumannii infections at Suez Canal University Hospitals, (2) the distribution of efflux pump genes AdeA &B, TetA, and TetB, and (3) the effect of efflux pump inhibitor (CCCP) on tetracycline-resistant isolates.MethodsClinical samples (457) were collected (blood, urine, sputum, ETA, pus, and pleural fluid), followed by A. baumannii isolation and identification, PCR detection of efflux pump genes, and detection of tetracycline susceptibility and its MIC before and after treatment with the efflux pump inhibitor (CCCP).ResultsA total of 31 A. baumannii isolates were recovered (6.78%). The highest rate of isolation was from the ICU (48.3%) from the ET aspirate samples (48.3%). The efflux system AdeA and TetB genes were distributed in 100% of isolates, whereas AdeB was found in 93.5% of isolates and the TetA gene in 87.1% of isolates. All A. baumannii isolates were MDR showing resistance to three or more classes of antibiotics. 45% of the isolates showed a 4-fold reduction of MIC and 12.9% showed a 2-fold reduction in the MIC.ConclusionsEfflux pump is an important mechanism for tetracycline resistance among A. baumannii isolates.

Determinants of Antibiotic Prescription in Outpatient Hospice: A Regional Observational Study.

Patients enrolling in hospice care are asked their preferences for antibiotic treatment. There is little information regarding which patients are more likely to receive antibiotics. To better inform discussions, we sought to characterize the use of antibiotics in the outpatient hospice setting. We performed a retrospective review of patients enrolled in outpatient hospice within the Mayo Clinic Health System from 1/1/2017 through 1/1/2023. We calculated what percent of patients received antibiotics based on Hospice Qualifying Condition (HQC), age at enrollment, sex, survival time, and Charlson Comorbidity Index and calculated adjusted odds ratios (aOR). We documented which antibiotics were prescribed based on HQC. Of 6452 patients identified, 1259 (19.5%) received antibiotic prescriptions. Cephalosporins were the most common class of antibiotics prescribed (22.8% of antibiotics prescribed), followed by fluoroquinolones (20.3%) and penicillin derivatives (14.9%). Patients with Pulmonary HQCs were most likely to receive antibiotics (28.6% aOR 1.85 [1.51-2.25]), those with neurologic HQCs were least likely (14.9% aOR 0.66 [0.53-0.83]). There was no difference of age for those receiving antibiotics (80.7yr) vs those not receiving (80.3yr [P = 0.25]), or for sex (male vs female aOR 1.10 [0.96-1.26). 4.6% of those surviving <7d received antibiotics (aOR .22 [0.17-0.29]), compared to 47.7% of those surviving >6mo (aOR 4.46 [3.50-5.69]). 19.5% of patients will receive antibiotics during their hospice course, with more frequent prescriptions in those surviving longer periods and those enrolled for pulmonary conditions. It is important to clarify patient preferences regarding antimicrobial utilization at the time of hospice enrollment.

Genomic Diversity and Potential Transmission and Persistence of Salmonella in the Cambodian Vegetable Supply Chain.

S. enterica isolates (n=78) obtained from the vegetable supply chain (farms, distribution centers, markets) in two Cambodian provinces (Siem Reap, Battambang) were sequenced and analyzed. In silico identification of serotypes and detection of antimicrobial resistance genes was performed using SISTR and ABRicate, respectively. Isolates' relatedness was assessed based on high-quality single nucleotide polymorphisms (hqSNPs) identified within each serotype using the CFSAN SNP pipeline. Among 29 detected serotypes, Paratyphi B var. Java was most abundant (n=14), followed by Hvittingfoss (n=11) and Thompson (n=7). Paratyphi B var. Java was mostly found in farms (n=5) and markets (n=6), Hvittingfoss within distribution centers (n=8), and Thompson at markets (n=4) and farms (n=3). Among Paratyphi B var. Java isolates, one phylogenetic clade contained four closely related isolates (0-1 SNP difference), collected at markets in different provinces on different days. Another clade contained two isolates that differed by one SNP, one obtained from a Battambang farm and one from a Siem Reap distribution center, suggesting a broad spread of Paratyphi B var. Java in the Cambodian vegetable supply chain. Hvittingfoss isolates clustered in two clades; one contained five identical isolates, four of which were obtained in different months from the distribution center and a farm in Battambang, suggesting possible transmission among supply chain stages. The second clade contained three isolates from the Battambang distribution center that differed by 0-1 SNP and were isolated in October and November, indicating possible persistence. Lastly, among 78 analyzed isolates, 14 carried antimicrobial resistance genes and seven out of these 14 carried genes with predicted resistance to more than three classes of antibiotics. Overall, highly similar isolates of Salmonella were identified over time and at different supply chain stages, suggesting possible persistence and transmission of Salmonella within and between supply chain stages.

Assemblage of Bacteria Communities and Resistome Enrichment by Dairy Flurries Along the Rhizosphere–Bulk Soil Continuum on Dairy Farms

The use of dairy slurries as organic fertilizer amendments is a common practice in agriculture as a cost-saving measure, as well as a residue management strategy. However, concerns related to the increase in antibiotic resistance in the environment under the scope of the One Health strategy are increasing. In this study, we aimed to assess resistome enrichment driven by dairy slurry application in four southern Chile dairy farms. Slurry pits, rhizospheres of Lolium perenne amended with those slurries, and bulk soils were sampled. Thirteen antibiotic-resistance genes (ARGs, tetA, tetG, tetM, tetQ, tetW, tetX, sul1, sul2, blaCTXM, blaOXA-1, blaTEM, ermB, and dfrA1) for five antibiotic classes (tetracyclines, sulfonamides, beta-lactams, macrolides, and trimethoprim–sulfamethoxazole), two related integrases (intl1 and intl2), and total bacteria (16S rRNA) abundance was measured by quantitative PCR (qPCR). Then, the abundance profiles of two enzyme-inactivated ARGs (tetX and blaTEM) were determined. The differences between the bacterial communities inhabiting the different sample types were explored with 16S rRNA metabarcoding. In general, all measured ARGs were detected in slurries. A decreasing trend in ARG copy numbers was observed with increasing soil depth, with the exception of tetX, whose abundance increased in the bulk soil at specific farms. The tetX and blaTEM communities revealed no differences in the relative abundance of variants in any of the samples. Finally, taxonomic and structural differences were found among all sample types. Thus, the enrichment of the sampled farm soil resistomes was driven by the application of the raw slurries as fertilizer.

Antibiotic usage within the first year of life has a protective effect against ulcerative colitis in South Korea: A nationwide cohort study

Antibiotic usage in early life has been proposed as a risk factor for inflammatory bowel disease, especially Crohn's disease. However, most studies were conducted in Western countries. We evaluated the association between antibiotic usage and the incidence of inflammatory bowel disease in the Asian population. This nationwide population-based retrospective cohort study included 2,941,889 South Korean infants born between 2007 and 2015, using the National Health Insurance Service database. We assessed whether antibiotic use was associated with the incidence of inflammatory bowel disease. Additionally, we conducted sensitivity analyses, considering protopathic bias and dietary variables. The Cox proportional hazards model was used. Among 2,941,889 infants, 2,566,390 (87 %) used antibiotics within a year after birth. Antibiotic usage within a year, number of antibiotic classes, and cumulative days of usage were shown to decrease the risk of ulcerative colitis. This association was particularly prominent with earlier antibiotic exposure. Penicillin was the only antibiotic class related to the reduced risk. The results were robust after adjusting for dietary variables and considering protopathic effect. Antibiotic exposure during the first year of life, particularly at a younger age, is linked to a reduced risk of early-onset ulcerative colitis in South Korea.

Co-selection of antibiotic and disinfectant resistance in environmental bacteria: Health implications and mitigation strategies.

The rapid emergence of co-selection between antimicrobials, including antibiotics and disinfectants, presents a significant challenge to healthcare systems. This phenomenon exacerbates contamination risks and limits the effectiveness of strategies to combat antibiotic resistance in clinical settings. This study aimed to investigate the prevalence and characteristics of bacteria in hospital environments that exhibit co-selection mechanisms and their potential implications for patient health, framed within the One Health perspective. Air and surface samples were collected from seven large hospitals and analyzed to detect antibiotic-resistant bacteria (ARB). The resistance profiles of isolated ARB to various disinfectants were determined. Bacterial species were identified using 16S rRNA gene sequencing, and the presence of antibiotic resistance genes (ARGs) and class 1 integrons (intI1) was investigated. A high percentage (85%) of samples contained ARB, with β-lactam resistance being the most frequently observed. Alarmingly, 94% of isolated ARB exhibited resistance to at least one disinfectant, and 91% demonstrated resistance to three or more disinfectants. Staphylococcus and Bacillus emerged as the dominant genera displaying co-selection. The presence of ARGs, including mecA (associated with methicillin resistance) and qacB (associated with disinfectant resistance), along with intI1, provided further evidence supporting co-selection mechanisms. These findings underscore the critical need for robust antimicrobial resistance surveillance and the prudent use of disinfectants in healthcare settings. Further research into co-selection mechanisms is essential to inform the development of effective infection control strategies and minimize the spread of resistant bacteria.

Targeted screening and profiling of massive components of colistimethate sodium by two-dimensional-liquid chromatography-mass spectrometry based on self-constructed compound database

Targeted screening and profiling of massive components of colistimethate sodium by two-dimensional-liquid chromatography-mass spectrometry based on self-constructed compound database

Flies as carriers of antimicrobial resistant (AMR) bacteria in Nigerian hospitals: A workflow for surveillance of AMR bacteria carried by arthropod pests in hospital settings.

The dissemination of antimicrobial resistant (AMR) bacteria by flies in hospitals is concerning as nosocomial AMR infections pose a significant threat to public health. This threat is compounded in low- and middle-income countries (LMICs) by several factors, including limited resources for sufficient infection prevention and control (IPC) practices and high numbers of flies in tropical climates. In this pilot study, 1,396 flies were collected between August and September 2022 from eight tertiary care hospitals in six cities (Abuja, Enugu, Kaduna, Kano, Lagos and Sokoto) in Nigeria. Flies were screened via microbiological culture and bacterial isolates were phenotypically and genetically characterised to determine carriage of clinically important antibiotic resistance genes (ARGs). Several clinically relevant ARGs were found in bacteria isolated from flies across all hospitals. blaNDM was detected in 8% of flies and was predominantly carried by Providencia spp. alongside clinically relevant Enterobacter spp, Escherichia coli and Klebsiella pneumoniae isolates, which all exhibited a multidrug resistant phenotype. mecA was detected at a prevalence of 6.4%, mostly in coagulase-negative Staphylococci (CoNS) as well as some Staphylococcus aureus, of which 86.8% were multidrug resistant. 40% of flies carried bacteria with at least one of the two ESBL genes tested (blaOXA-1 and blaCTX-M-15). This multi-site study emphasised that flies in hospital settings carry bacteria that are resistant to multiple classes of antibiotics, including both routinely used and reserve antibiotics. A greater understanding of the global clinical significance and burden of AMR attributable to insect pests is required.

Antimicrobial-resistant Raoultella planticola isolated from preweaned dairy calf feces.

Raoultella planticola is an emerging opportunistic pathogen closely related to members of the Klebsiella genus. Genomic characterization of R. planticola isolates recovered from food animals is lacking. Here we describe the antimicrobial resistance genes, virulence factors, plasmid replicons, and phylogeny of three antimicrobial-resistant R. planticola isolates recovered from the feces of three dairy calves within 48 hours of birth. The genomes of the three R. planticola isolates were sequenced on a NextSeq 2000 platform using paired-end sequencing. The raw reads were trimmed using Trimmomatic and assembled using SPAdes v 3.15.4. Antimicrobial resistance genes, virulence factors and plasmid replicons were identified using ABRicate. Single nucleotide polymorphisms were identified among the genomes using the Harvest package and phylogenies were inferred using RAxML. In total, nine different ARGs known to confer resistance to at least five different classes of antibiotics were detected among the three R. planticola genomes. These include blaPLA, a β-lactamase found only in R. planticola, fosfomycin resistance gene fosA, and a sequence aligned with oxqAB, an efflux pump conferring resistance to antibiotics including fluoroquinolones. Each genome encoded between four and seven ARGs, with three considered genotypically to be multidrug-resistant (MDR). Two of the three genomes harbored plasmids, and all three encoded 41 to 42 virulence factors, including iron scavenging genes sitABCD. Results of this study demonstrate the presence of diverse antimicrobial-resistant R. planticola, isolated from the feces of healthy dairy calves, that had some virulence factors that may cause human disease.

N-Acetyl Cysteine and Vitamin C Modulate the Antibiotic Efficacy Against Escherichia coli Cells.

Supplements with their own beneficial effect on hosts are consumed by us. N-acetyl cysteine (NAC) and Vitamin C (Vit C) are antioxidants and supplements, consumed for their beneficial properties. The present investigation evaluates the effect of their antioxidant property on antibiotic efficacy against Escherichia coli cells from different physiological states, including exponential and stationary-phase, cell aggregates, and in-vitro stress-induced persister cells. Survival was measured in cfu/mL by cfu (colony-forming unit) counting, with efficacy determined by log-fold change in survival by comparing CFUs in antibiotics alone and antibiotic + antioxidant combinations. Fluoroquinolones in the presence of NAC reduced ∼1 log CFUs of log-phase and persister cells, while Vit C reduced CFUs (∼1-3-log increase) of cells from all physiological states. Aminoglycosides results were inconclusive; streptomycin's activity declined (∼1-3-log increase in survival), whereas amikacin's activity potentiated (∼1-log reduction in cfu/mL). Rifampicin's showed reduced activity (∼2-3 log increase in survival) with Vit C in all the states and a ∼1-2 log increase with NAC, especially in cell aggregates and persisters. Beta-lactams activity showed variability, with amoxicillin and ampicillin not being influenced, but ceftriaxone showed significant reduction of efficacy (∼2-3-log increase in survival) in all the treatments. The findings suggest that the overall impact of antioxidants on antibiotic efficacy varies depending on the antibiotic class.

Microbiological profiles of infectious corneal ulcers in Derbyshire and North Nottinghamshire-a 10-year analysis.

To assess the spectrum of organisms causing microbial keratitis and their in-vitro anti-microbial sensitivities out of 2 hospitals in the East Midlands Region of the United Kingdom. A retrospective review was undertaken of all patients who underwent corneal scrapes for infectious keratitis between 2011 and 2021 at Royal Derby Hospital (RDH) in Derby and between 2009 and 2021 at King's Mill Hospital in Mansfield. In total, the results of 645 corneal scrapes (from 622 patients) were analysed after exclusions. Of these, 307 (47.6%) yielded positive cultures. The mean patient age was 52.6 ± 22.1years (Mean ± St Dev) across both sites and 332 (51.4%) were from female patients. At RDH, there were 195 positive corneal scrape cultures, from which 250 species of organisms were isolated. At RDH, 64% (160/250) were Gram-positive bacteria, 32% (81/250) were Gram-negative bacteria, 2.4% (6/250) were Acanthamoeba species and 1.2% were fungi (3/250). At KMH, there were 112 positive cultures, from which 128 species of organisms were isolated. 14 corneal scrapes from KMH were polymicrobial. At KMH, 96% (123/128) were bacterial (51% Gram positive, 45% Gram negative), 3/128 (2.3%) were fungi and 2/128 (1.6%) were Acanthamoeba. Sensitivity testing confirmed that the fluoroquinolone class of antibiotics appeared to be effective against the majority isolates across the two hospital sites. There are differences in microbiological profiles between these neighbouring hospitals covering neighbouring populations. Despite these differences, reassuringly, the current first-line fluoroquinolone monotherapy treatment is an appropriate first-line treatment for both hospital sites.

P-1465. Real-World Treatment Patterns in Adult Patients Infected with Extra-Intestinal Pathogenic Escherichia Coli in the United States

Abstract Background Extraintestinal pathogenic E. coli (ExPEC) are often treated with multiple classes of antibiotics, however, real-world treatment patterns are poorly characterized. We sought to identify evidence about treatments used for adult patients infected with ExPEC in the US. Figure 1 PRISMA flowchart Methods A systematic literature review was conducted in EMBASE, MEDLINE, and MEDLINE In-Process databases to identify US studies of treatments used for ExPEC infections in real world settings, published Jan. 2010–Sept. 2023. Figure 2 Antibiotic classes used for the treatment of ExPEC infections observed across studies Results Seven publications met eligibility criteria for inclusion (Fig 1). Infections were usually community acquired (CA) (67.8% - 94.3%). Median treatment duration was reported in 3 studies and ranged 2.72 - 13 days. While various antibiotic classes used to treat ExPEC infections were reported, broad-spectrum antibiotics were used frequently (Fig 2). Patients with CA E. coli pneumonia and older patients (≥70 yrs.) with urinary tract infection commonly received fluoroquinolones (FQ) or cephalosporins. Carbapenem was frequently prescribed in patients with ceftriaxone-resistant E. coli and those with extended spectrum β-lactamase producing E. coli (ESBL-EC). Treatment patterns following an index visit were described in 3 studies; patients often received multiple antibiotics, one study reported that 82.8% of patients received &amp;gt;1 antibiotic course. Among patients with non-ESBL-EC and those with E. coli bacteremia, ceftriaxone was the most frequent antibiotic used for de-escalation of empiric piperacillin-tazobactam following susceptibility cultures. Adequate therapy (i.e. antibiotic/pathogen match) was reported to be more likely among patients with non-ESBL-EC compared with ESBL-EC and among patients admitted to hospitals during weekends, while inadequate therapy was more common in patients with E. coli ST131. One study reported that 39% of FQ-resistant patients were switched to adequate therapy. Conclusion These findings highlight the complexity of managing ExPEC infections which involve a wide range of antibiotics and often &amp;gt; 1 antibiotic course contributing to the rise of antimicrobial resistance (AMR) with increased morbidity and mortality. There is an unmet need for more data on treatment patterns and associated AMR rates for specific real-world treatment patterns. Disclosures Brenda Rattanavong, PharmD, Janssen Global Services, LLC: As a medical writer, I receive payment from the sponsor to support drafting of the abstract. Sanjukta Basu, Ph.D, Amaris Consulting: Advisor/Consultant Atara Laor, BSc., Amaris Consulting: Advisor/Consultant Liga Bennetts, PhD, Amaris Consulting: Advisor/Consultant Ziyan (Jenny) Wei, Msc, Amaris Consulting: Advisor/Consultant Antoine El Khoury, PhD, Janssen Global Services: Advisor/Consultant|Janssen Global Services, LLC: Employee of Janssen Global Services, LLC Jeroen Geurtsen, PhD, Janssen Vaccines &amp; Prevention BV: Advisor/Consultant|Janssen Vaccines &amp; Prevention BV: Employee of Janssen Vaccines &amp; Prevention BV Nina Ahmad, MD, Janssen Global Services, LLC: Employee of Janssen Global Services, LLC Maureen P. Neary, PhD, MS, Janssen Global Services, LLC: Employee of Janssen Global Services, LLC

P-1829. Genomic Characterization of Clinically Significant Isolates and Its Effects on Clinical Outcomes, 2022 to 2024

Abstract Background Antimicrobial resistance has evolved into a complex global issue involving many clinically relevant organisms. Among these pathogens, carbapenem-resistant organisms (CROs) are of particular concern due to their limited treatment options and high mortality rates. In collaboration with Solu, whole-genome sequencing (WGS) was performed on clinical isolates recovered from our patient population to gain a better insight into resistance mechanisms present and their direct effect on clinical outcomes. Methods For genomic characterization (WGS), a total of 109 carbapenem resistant isolates across three clinically relevant bacterial groups (Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii complex) were sequenced. Solu utilized a hybrid assembly approach utilizing both long reads generated with Oxford Nanopore Technologies (ONT) complemented by Illumina short reads for the reconstruction of bacterial genomes. Results Multilocus sequence typing (MLST) revealed genetic diversity among all three groups of bacterial isolates. Among members of the family Enterobacterales, there were eight distinct sequence types: ST-131, ST-1431, ST-167, ST-2155, ST-361, ST-410, ST-685 and ST-405. A. baumannii complex strains mostly comprised of ST-2 and ST-1022. The presence of numerous sequence types was observed with the P. aeruginosa isolates, highlighting the biocomplexity within our patient population. Furthermore, genomic analysis of these isolates disclosed a broad range of antimicrobial resistance genes that span across several classes of antibiotics. Isolates across all genera harbored plasmid-mediated carbapenemase genes bla-NDM-5, bla-NDM1, bla-OXA-48 and bla-OXA23. Interestingly, cefiderocol resistance was primarily associated with the Escherichia coli ST-405 strain containing AMR gene bla-NDM5. Patients associated with a carbapenemase-producing strain were observed to have higher mortality rates (12.8%) and longer length of hospital stay (25.6%). Conclusion By having a comprehensive insight into the genomic composition of isolates that make up our patient population, we can provide a more targeted medical treatment approach and investigate and better prevent transmission events. Disclosures All Authors: No reported disclosures

P-1146. Environmental Surfaces in Healthy Households as Reservoirs of Extended-Spectrum Cephalosporin-Resistant Enterobacterales in the Community

Abstract Background Community-acquired extended-spectrum cephalosporin resistant (ESCr)-Enterobacterales (E) are increasing in healthy populations, yet the sources of acquisition are unknown. We assessed household (HH) environmental surface samples (HS) in St. Louis, MO, to identify the surfaces most frequently contaminated with ESCr-E and the associated mechanisms of antibiotic resistance (AR). Figure 1. Enterobacterales within households. Methods From 139 HHs, samples from 21 HS and inguinal fold (IF) samples of healthy adults and children were cultured for bacteria. Families were recruited from outpatient pediatric settings. Bacterial identification and antibiotic susceptibility testing were conducted (Vitek®2, bioMérieux). Molecular characterization of ESCr-E was performed by PCR detection of beta-lactamase (bla) and plasmid-mediated quinolone resistance (PMQR) genes. Whole genome sequencing (WGS) was performed on select HH with &amp;gt; 1 colonized HS to evaluate for genetic relatedness, plasmids, and AR genes. A HH cluster was defined as &amp;lt; 15 single nucleotide polymorphism differences between 2 isolates. Figure 2. ESCR Enterobacterales by genera Results Of 581 IF and 2801 HS, the majority harbored bacteria (IF, 97-100% and HS, 79-100%) and gram-negative bacteria, (IF, 72-80% and HS, 75-87%). IF colonization with Enterobacterales was ∼23% and ranged from 7-60% on HS; The most common ESCr-E genera were Enterobacter (79%), Pantoea (10%), and Klebsiella (7%). ESCr-E were found in 2% of IF. HS most notably colonized with ESCr-E were the kitchen sink faucet (9%), oven door handle (4%), sofa (4%), bathroom sink faucet (3%) and bed sheets (3%), (Figures 1-3). ESBL-E were recovered from ∼2% of HHs. MDR-E (&amp;gt; 3 antibiotic classes) were found in 4% of HHs. WGS of 20 E. cloacae from 4 HHs revealed within HH clusters (Figure 4). Of interest, we found that among E. cloacae, 10/20 (50%) contained AR plasmids (ex. IncFI, IncFII, IncX5, IncHI2, Col440I); bla, other AR (ex. PMQR, aminoglycoside, sulfa, fosfomycin) and virulence genes were detected in E. cloacae in all HHs. We also found related E. cloacae strains in 2 HHs (ST108), indicating local strains circulating potentially related to a common exposure. Figure 3. AR Enterobacterales by surface. Conclusion ESCr-E are present in healthy household environments. Future directions will be to identify candidate clinical and epidemiological features linked with ESCr-E HH colonization. Figure 4. Genetic relatedness among household Enterobacter cloacae Disclosures Ahmed Babiker, MBBS, Beckman Coulter Inc.: Advisor/Consultant

P-1322. Transmission Dynamics of Escherichia coli Sequence Type 131 Amongst Community Dwelling Households: A Prospective Cohort Study

Abstract Background Escherichia coli sequence type 131 (E. coli ST131) is a global pandemic clone associated with the rapid dissemination of CTX-M–class extended spectrum β-lactamase (ESBL) genes, conferring resistance to several antibiotic classes, and is a major cause of both healthcare and community-acquired extraintestinal pathogenic E. coli (ExPEC) infections. The drivers of E. coli ST131 pandemicity are not well-understood. Figure 1. Prospective cohort study enrollment flowchart Methods Between February 2017 to November 2018, 34 hospitalized patients with E. coli positive cultures (including half with ST131-positive cultures) and their household coresidents were recruited to a prospective cohort study in which all household members provided up to 12 stool samples at 2-6 week intervals. The samples were screened for E. coli ST131 isolates using quantitative polymerase chain reaction (qPCR), and short-read whole genome sequencing (WGS) was conducted on all E. coli ST131-positive isolates. Figure 2. Model estimates of E. coli ST131 acquisition rate and carriage duration Results Nine individuals (7.25%) carried E. coli ST131 for a median of 86.35 days [80% CrI: 30.03-188.8] (over three times higher than the cohort average of 27.33 days [80% CrI: 20.00-36.74]) and at high densities. The household coresidents of these individuals acquired E. coli ST131 at approximately twice the rate of those who did not coreside with a persistent high-density carrier (0.031 per day [80% CrI: .012-.10] and 0.016 per day [0.006-0.05], respectively; Odds Ratio: 2.61 [95% CI: 1.36 to 5.00] (p &amp;lt; 0.01)). WGS analysis identified a high degree of sequence similarity between E. coli ST131 isolates obtained from different individuals and at multiple non-sequential timepoints in four of the nine families in which a high-density persistent carrier was resident, indicating potential repeated transmission events. Multivariate and univariate regression analysis of risk factors associated with E. coli ST131 acquisition Conclusion These findings indicate that a proportion of high-density asymptomatic carriers in the community may act as reservoirs for E. coli ST131, with frequent transmission to household contacts representing a key driver of E. coli ST131’s pandemic success. Further studies in other settings are needed to understand high-density persistent carrier status and address this potential community-level reservoir in order to contain this multi-resistant pathogen and reduce its clinical impact. Disclosures Paul Tambyah, MBBS (S'pore), Diplomate, American Board of Internal Medicine and Infectious Diseases, Moderna: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support